Cat food compositions for treating chronic kidney disease

Abstract

The present disclosure relates to food compositions comprising an effective amount of one or more tripolyphosphate salt, as a source of inorganic phosphorus, for use in a method for treating and / or delaying the progression of chronic kidney disease in a cat in need thereof.

Description

[0001] CAT FOOD COMPOSITIONS FOR TREATING CHRONIC KIDNEY DISEASE

[0002] CROSS REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of priority to European Application No. 23213031.0, filed November 29, 2023, the contents of which are incorporated herein by reference in their entirety.

[0004] FIELD OF THE DISCLOSURE

[0005] The present disclosure relates to the field of cat food compositions. In particular, the present disclosure relates to food compositions and methods for treating and / or preventing and / or delaying the progression of chronic kidney disease in a cat in need thereof.

[0006] BACKGROUND OF THE DISCLOSURE

[0007] In good health, feline kidneys carry out several vital functions, primarily involving the filtration of blood and the production of urine. Therefore, any issues affecting kidney function can lead to a range of health issues for a cat. Among the many different kidney diseases that may affect cats, chronic kidney disease (CKD) is the most common.

[0008] Thus, chronic kidney disease is a prevalent and challenging health concern affecting feline populations. Among cats, chronic kidney disease is widely recognized, with an estimated prevalence of about 5%. Although chronic kidney disease occurs in all ages with noted variations in its underlying causes, its prevalence increases with age, affecting up to about 40% of cats above the age of 15 years.

[0009] Chronic kidney disease is characterized by a progressive deterioration in renal function over the life of a cat, encompassing a diverse range of manifestations rather than a singular pathology. Chronic kidney disease in cats can generally progress through several stages, including the loss of renal reserve, azotemia, which is an increased creatinine level with minimal or no clinical signs, and eventually at the end can culminate in renal failure (with uremia being a non-limitative example of renal failure). Kidneys inherently possess a significant reserve capacity, as only about 30% of their full potential is necessary for normal functioning. Overtime, various factors such as advanced age, diseases, and medications that harm the kidneys can diminish this capacity. Renal insufficiency occurs when renal function decreases, typically becoming evident when around 70% of kidney function has been lost, leaving only about 30% of the kidney's capacity available.

[0010] Signs of chronic kidney disease are generally not apparent during the phases of loss of renal reserve, making early detection challenging. Azotemia manifests as abnormally high concentrations of creatinine, and a lower urinary concentrating ability. In the azotemic phase, renal function is significantly reduced, though clinical symptoms may be mild and go unnoticed. Renal failure characterized by uremia which manifests as abnormally high concentrations of urea and other non-protein nitrogen containing substances in the blood, is the phase marked by overt clinical signs.

[0011] Chronic kidney disease can be associated with various clinical signs, including polyuria (increased urine production), polydipsia (increased thirst), weight loss, lethargy, electrolyte imbalances, and metabolic disturbances. The disease often advances over time, leading to complications such as hypertension, anemia, mineral imbalances, and bone demineralization ultimately affecting the overall health and longevity of the affected cat.

[0012] A notable factor contributing to chronic kidney disease progression is the postprandial elevation in plasma phosphorus concentration, which subsequently amplifies the filtered phosphorus load presented to each nephron in the feline kidney. This increased plasma phosphorus level triggers the secretion of parathyroid hormone (PTH) acutely, whereas chronic elevation results in augmented secretion of fibroblast growth factor 23 (FGF23). Both FGF23 and PTH collaborate in diminishing phosphorus reabsorption from the renal proximal tubules by decreasing the expression of NaPi2a transporters in the proximal tubular cells' apical membranes. Consequently, the higher tubular phosphorus concentration ensues from this rise in plasma phosphorus concentration.

[0013] Experimental evidence proposes that if the concentration of phosphorus is raised, it triggers stress within the proximal tubular cells of the kidneys. This stress is attributed to the formation of calciprotein crystal nanoparticles that can block lysosomal function, delay autophagy, and activate oxidative stress leading to kidney dysfunction.

[0014] Thus, while phosphorus is an essential nutrient for cats, and companion animals in general, a high level of soluble phosphorus in the blood may be implicated as a cause of chronic kidney diseases (Alexander et al., Br J Nutr. 2019 Feb 14;121(3):249-269). Consequently, the pet industry has been actively researching alternatives to mitigate the detrimental effects of inorganic phosphorus on the kidney health and function of cats as it incorporates sources of inorganic phosphorus into their food compositions.

[0015] Current cat food compositions having a protective effect on renal issues are formulated with low levels of phosphorus and have been shown to slow down the progression of chronic kidney disease in cats. However, it has been reported that different sources of phosphorus might not have the same effect on kidney health and function. For instance, it has been observed that, when fed at the same level within a food composition, sources of inorganic phosphorus, such as phosphate salts, can cause a dose-dependent peak in plasma phosphorus level potentially inducing acute renal injuries, while sources of organic phosphorus, derived from bones and tissues, were considered benign or at least harmless for the kidney (Alexander et al., BrJ Nutr. 2019 Feb 14; 121 (3): 249-269).

[0016] Inorganic phosphorus derived from phosphorus salt can induce a faster and higher increase in plasma phosphorus than organic phosphorus derived from raw materials suitable to be used in animal food compositions. Furthermore, studies have demonstrated that the inclusion of phosphate salts, such as tripolyphosphate salt, in animal food compositions could be considered as deleterious for kidneys function depending on the dose of inorganic phosphorus (Colthered et al. British Journal of Nutrition 2019; 121 (3):270-284).

[0017] Consequently, there remains a need to identify alternative strategies for treating and / or preventing and / or delaying the progression of chronic kidney disease in cats.

[0018] There is a need for novel food compositions and / or methods for treating and / or preventing and / or delaying the progression of chronic kidney disease in a cat in need thereof.

[0019] The present disclosure has for purpose to satisfy all or part of the above- mentioned needs.

[0020] SUMMARY

[0021] An aspect of the present disclosure relates to a food composition including from about 0.1 g / Mcal to about 1.5 g / Mcal of inorganic phosphorus and comprising an effective amount of one or more tripolyphosphate salt, as a source of inorganic phosphorus, for use in a method for treating and / or preventing and / or delaying the progression of chronic kidney disease in a cat in need thereof. Another aspect of the present disclosure relates to a food composition including from about 0.1 g / Mcal to about 1.5 g / Mcal of inorganic phosphorus and comprising an effective amount of one or more tripolyphosphate salt, as a source of inorganic phosphorus, for use in a method for treating and / or delaying the progression of chronic kidney disease in a cat in need thereof.

[0022] In some embodiments, the one or more tripolyphosphate salt consists of sodium tripolyphosphate (STPP), potassium tripolyphosphate (KTPP) or a mixture thereof.

[0023] In some embodiments, the one or more tripolyphosphate salt consists of potassium tripolyphosphate.

[0024] In some embodiments, the one or more tripolyphosphate salt consists of sodium tripolyphosphate.

[0025] In some embodiments, the food composition for use as described herein can include about 1.0 g / Mcal or less of inorganic phosphorus.

[0026] In some embodiments, the food composition for use as described herein can include from about 0.1 g / Mcal to about 1.0 g / Mcal of inorganic phosphorus.

[0027] In some embodiments, the food composition for use as described herein can include from about 0.5 g / Mcal to about 1.0 g / Mcal of inorganic phosphorus.

[0028] In some embodiments of the food composition for use as described herein, at least about 0.2 g / Mcal of inorganic phosphorus can originate from the one or more tripolyphosphate salt.

[0029] In some embodiments of the food composition for use as described herein, about 0.2 g / Mcal or more, or about 0.3 g / Mcal or more, or about 0.4 g / Mcal or more, or about

[0030] 0.5 g / Mcal or more, or about 0.6 g / Mcal or more, or about 0.7 g / Mcal or more, or about

[0031] 0.8 g / Mcal or more, or about 0.9 g / Mcal or more, or about 1 .0 g / Mcal or more, or about

[0032] 1.1 g / Mcal or more, or about 1 .2 g / Mcal or more, or about 1 .3 g / Mcal or more, or about

[0033] 1.4 g / Mcal or more of inorganic phosphorus can originate from the one or more tripolyphosphate salt.

[0034] In some embodiments of the food composition for use as described herein, the inorganic phosphorus can originate from one or more inorganic pyrophosphate and one or more tripolyphosphate salt.

[0035] In some embodiments, the total amount of inorganic phosphorus can originate from one or more tripolyphosphate salt.

[0036] In some embodiments, the food composition for use as described herein can include a further source of minerals or ash. In some embodiments, the food composition for use as described herein can include calcium (Ca), sodium (Na), potassium (K) and chlorine (Cl).

[0037] In some embodiments, the food composition for use as described herein can include calcium and phosphorus in such a way that the weight ratio of calcium to phosphorus is characterized by being equal or higher than 1 .

[0038] In some embodiments, the food composition for use as described herein can include calcium and phosphorus in such a way that the weight ratio of calcium to phosphorus is characterized by ranging from 1 to 2.

[0039] In some embodiments, the food composition for use as described herein can include calcium and phosphorus in such a way that the weight ratio of calcium to phosphorus is characterized by ranging from 1.2 to 1.8.

[0040] In some embodiments, the food composition for use as described herein can include calcium and phosphorus in such a way that the weight ratio of calcium to phosphorus is characterized by ranging from 1.3 to 1.4.

[0041] In some embodiments, the food composition for use as described herein can include from about 1 g / Mcal to about 5 g / Mcal of potassium.

[0042] In some embodiments, the food composition for use as described herein can include protein, fat, fibers, and / or vitamins.

[0043] In some embodiments, the food composition for use as described herein can include, on a dry matter basis, from about 20% to about 50% by weight of protein.

[0044] In some embodiments, the food composition for use as described herein can include, on a dry matter basis, from about 20% to about 50% by weight of protein providing from a protein source.

[0045] In some embodiments, the food composition for use as described herein can include, on a dry matter basis, from about 5% to about 25% by weight of fat.

[0046] In some embodiments, the food composition for use as described herein can include, on a dry matter basis, from about 5% to about 25% by weight of fat providing from a fat source.

[0047] In some embodiments, the food composition for use as described herein can include, on a dry matter basis, from about 4% to about 15% by weight of fiber.

[0048] In some embodiments, the food composition for use as described herein can include, on a dry matter basis, from about 4% to about 15% by weight of fiber providing from a fiber source. In some embodiments, the food composition for use as described herein can include preservatives, trace elements and / or coloring.

[0049] In some embodiments, the food composition for use as described herein can include a diluent and / or an excipient.

[0050] In some embodiments, the food composition for use as described herein can be a nutritionally complete and balanced food composition or a functional complement.

[0051] In some embodiments, the food composition for use as described herein can be a nutritionally complete and balanced food composition.

[0052] In some embodiments, the food composition for use as described herein can be a wet, a dry or a semi-moist food composition.

[0053] In some embodiments, the food composition for use as described herein can be a dry food composition, in particular having a moistures content ranging from about 5 % to about 12% by weight, relative to the total weight of the food composition.

[0054] In some embodiments, the food composition for use as described herein can have a Metabolizable Energy ranging from about 400 kcal / kg to about 5,000 kcal / kg, as measured according to the NRC 2006.

[0055] In some embodiments, the food composition for use as described herein can have a Metabolizable Energy ranging from about 3,000 kcal / kg to about 5,000 kcal / kg, as measured according to the NRC 2006.

[0056] In some embodiments, the food composition for use as described herein can have a Metabolizable Energy ranging from about 3,800 kcal / kg to 3,900 kcal / kg, as measured according to the NRC 2006.

[0057] In some embodiments, the food composition for use as described herein, wherein chronic kidney disease can affect a cat involving the deterioration of renal parenchyma; the loss of functional nephrons; and / or the damage and / or the deterioration of the glomerulus.

[0058] BRIEF DESCRIPTION OF THE FIGURES

[0059] Figure 1 represents a box plot graph showing the serum pyrophosphate concentration in a group of fourteen cats before feeding (baseline) and 60 minutes after feeding a food composition containing sodium tripolyphosphate as a source of inorganic phosphorus (n = 14). Ordinate: Serum pyrophosphate concentration in micromolar (pM). Abscissa: Measurement of the pyrophosphate concentration in cats before feeding (0 minute) and 60 minutes after having fed the food composition. Figure 2 represents a box plot graph showing the serum pyrophosphate concentration in a group of fourteen cats before feeding (baseline) and 60 minutes after feeding a food composition containing a combination of 50% by weight of monopotassium phosphate (MKP) and 50% by weight of inorganic pyrophosphate (Pipi) as a source of inorganic phosphorus (n = 14). Ordinate: Serum pyrophosphate concentration in micromolar (pM). Abscissa: Measurement of the pyrophosphate concentration in cats before feeding (0 minute) and 60 minutes after having fed the food composition.

[0060] Figure 3 represents a box plot graph showing the area under the curve (AUC) of serum phosphorus concentration in a group of fourteen cats 60 minutes after feeding diet A or diet B comparing to baseline (before feeding). Ordinate: AUC between baseline and 60 minutes after feeding. Abscissa: Diet A is a food composition containing sodium tripolyphosphate as a source of inorganic phosphorus. Diet B is a food composition containing a combination of monopotassium phosphate and inorganic pyrophosphate as a source of inorganic phosphorus. *p<0.05

[0061] DETAILED DESCRIPTION OF THE DISCLOSURE

[0062] Bioavailability of inorganic phosphorus and its impact on the kidney can depend on the source of inorganic phosphorus, and more particularly on the phosphorus salt included within a food composition. Other factors such as the ratio between calcium and phosphorus can also influence the bioavailability of inorganic phosphorus.

[0063] Previous in vitro assays reveal that inorganic pyrophosphate, as a source of inorganic phosphorus, could exhibit inhibitory effects on the formation of crystalline secondary nanoparticles. Those crystalline particles are responsible for lysosomal dysfunction, inhibiting autophagy and predisposing to oxidative stress of the renal tubular cells, thus impacting the kidney health. However, curiously, previous studies reveal that dietary pyrophosphate within food compositions can not necessarily increase the plasma pyrophosphate level sufficiently to confer its protective effect against the toxic impact of the formation of crystalline secondary nanoparticles.

[0064] As demonstrated in the example section of the present disclosure, it has been surprisingly found that a tripolyphosphate salt, as a source of inorganic phosphorus within a food composition, could promote an increase of the plasma pyrophosphate level. The study on phosphate kinetics, conducted after feeding cats a food composition containing different sources of inorganic phosphorus, reveals that, contrary to what was expected, a tripolyphosphate salt can significantly raise the plasma pyrophosphate concentration, contrary to a combination of an inorganic pyrophosphate and a monophosphate salt.

[0065] Without wishing to be bound to any particular theory, it is believed that once fed by the cats, the intestinal alkaline phosphatase breaks down a tripolyphosphate salt molecule to release one pyrophosphate molecule and one phosphate molecule. In contrast, the use of inorganic pyrophosphate as a source of phosphorus, when combinate with a monophosphate salt, is rapidly metabolized into two monophosphate molecules.

[0066] Consequently, an advantage of a food composition as disclosed herein resides in that tripolyphosphate is more slowly metabolized by intestinal alkaline phosphatase than dietary inorganic pyrophosphate, combined with a monophosphate salt. A food composition including one or more tripolyphosphate salt can lead to an increase in plasma pyrophosphate level post-feeding. Thus, this could protect the damage of the kidney in cats by avoiding excessive plasma phosphorus level and by exhibiting inhibitory effects on the formation of crystalline secondary nanoparticles to treat and / or prevent kidney cells toxicity.

[0067] Subsequently, it has been demonstrated that when a tripolyphosphate salt was incorporated in a food composition in an amount that introduces about 1 g / Mcal or less of inorganic phosphorus, no longer adverse or toxic effects were reporter to the fed animals.

[0068] An objective of the present disclosure is to provide a food composition, which can be nutritionally complete and balanced, comprising an effective amount of one or more tripolyphosphate salt for use in a method for treating and / or preventing and / or delaying the progression of chronic kidney disease (CKD) in a cat in need thereof.

[0069] It is also provided methods of treating and / or preventing and / or delaying the progression of chronic kidney disease in a cat.

[0070] Definitions

[0071] The terms used in this disclosure generally have their ordinary meanings in the art, within the context of this disclosure and in the specific context where each term is used. Certain terms are discussed below, or elsewhere in the specification, to provide additional guidance in describing the compositions and methods of the disclosure and how to make and use them.

[0072] Exemplary methods and food compositions are described below, although methods and food compositions similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0073] Numeric ranges are inclusive of the numbers defining the range. The headings provided herein are not limitations of the various aspects of the disclosure. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.

[0074] All publications and other references mentioned herein are incorporated by reference in their entirety.

[0075] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a source” can include a mixture of at least two sources.

[0076] The term “about”, as used herein, means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. In general, the term “about” can modify a numerical value above and below the stated value by a variance of, for instance, 10 percent, up ordown (higher or lower). In some embodiments, the term indicates deviation from the indicated numerical value by ±15%, ±10%, ±5%, ±4%, ±3%, ±2%, or ±1%.

[0077] As used herein, the terms “comprise”, “comprising”, “include”, “including” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a food composition, a process or a method that includes or comprises a list of nutriments, ingredients, or steps which does not include only those nutriments, ingredients, or steps but can include other nutriments, ingredients, or steps not expressly listed or inherent to such food composition, process or method. The term “consisting of” implies the inclusion of the stated element(s), to the exclusion of any additional nutriments, ingredients, or steps. The term “consisting essentially of” implies the inclusion of the stated elements, and possibly other element(s) where the other element(s) do not materially affect the basic and novel characteristic(s) of the disclosure. It is understood that the different embodiments of the disclosure using the term “including” or equivalent cover the embodiments where this term is replaced with “consisting of” or “consisting essentially of’.

[0078] As used herein, the term “effective amount” refers to an amount or concentration of a specific ingredient within a food composition that is sufficient to produce the desired intended effect or function for which it is included. The effectiveness of the amount can vary depending on the specific ingredient, the intended outcome, and the target concentration of nutriment for the food composition. In the context of the present disclosure, an effective amount of one or more tripolyphosphate salt(s), as a source of inorganic phosphorus, in a food composition can depend on the specific target amount of inorganic phosphorus to be included in the food composition. Specifically, an effective amount of tripolyphosphate salt, as a source of inorganic phosphorus, in a food composition should not exceed an amount that provides more than 1.5 g / Mcal of the total inorganic phosphorus. Illustratively, an effective amount of one or more tripolyphosphate salt within a food composition as described herein can be an amount of about 0.3 g / Mcal, or about 0.4 g / Mcal, or about 0.6 g / Mcal, or about 0.9 g / Mcal, or about 1.2 g / Mcal, or about 1.5 g / Mcal, or about 1.8 g / Mcal, or about 2.1 g / Mcal, or about 2.4 g / Mcal, or about 2.7 g / Mcal, or about 3.0 g / Mcal, or about 3.3 g / Mcal, or about 3.6 g / Mcal, or about 3.9 g / Mcal, or about 4.2 g / Mcal, or about 4.5 g / Mcal, or about 4.8 g / Mcal, or about 5.1 g / Mcal, or about 5.4 g / Mcal, or about 5.7 g / Mcal, or about 6.0 g / Mcal of one or more tripolyphosphate salt.

[0079] In the detailed description herein, references to “embodiment,” “an embodiment,” “one embodiment,” “in some embodiments,” or any other variation thereof, indicate that the described embodiment(s) can include particular nutriments, ingredients, or steps, but every embodiment might not necessarily include the particular nutriments, ingredients, or steps. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular nutriment, ingredient, or step is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such nutriments, ingredients, or steps in connection with other embodiments whether or not explicitly described. After reading the description, it will be apparent to one skilled in the relevant art(s) how to implement the disclosure in alternative embodiments.

[0080] As used herein, the term “food composition” covers all of foodstuff, diet, food supplement or a material that can sustain growth, repair and vital processes of a cat. Such a food composition can contain one or more ingredients, such as source of nutriments. Nutriments of a food composition can be typically proteins, fibers, carbohydrates and / or fats, which can be used in combination in the body of an organism to sustain growth, repair and vital processes and to furnish energy (defined with the metabolizable energy (ME)). Carbohydrates includes NFE (Nitrogen free extract). A food composition as disclosed herein can also contain supplementary ingredients such as substances or additives, for example, flavoring, minerals and vitamins. A food composition as disclosed herein can further contain a carrier, a diluent, and / or an excipient.

[0081] In the context of the present disclosure, an "ingredient" refers to any individual component or substance that is intentionally included in the formulation of a food composition. An ingredient can be of various types, such as sources of proteins, carbohydrates, fats, vitamins, minerals, flavorings, preservatives, and / or other additives. An ingredient can be a raw material, a raw material by-product, an additive and / or a nutritional supplement. The selection and combination of ingredients can be critical in producing a complete and balanced food composition for a cat.

[0082] As used herein, “nutritionally complete and balanced” means that the composition of the present disclosure comprises all the essential nutrients in appropriate proportions to meet a cat's dietary requirements for maintaining overall health and well-being. A nutritionally complete and balanced food composition can maintain the body weight of the cat without significant change with the Body Condition Score (BCS). A nutritionally complete and balanced cat food composition ensures that the cat receives all the necessary nutrients for optimal health, minimizing the risk of nutritional deficiencies or imbalances that could lead to health issues over time. Specifically, a nutritionally complete and balanced food composition can contain all known required nutrients for the intended recipient of the food composition, in all appropriate amounts and proportions based, for example, on recommendations of recognized and competent authorities in the field of cat nutrition, such as the Association of American Feed Control Officials (AAFCO) or the European Pet Food Industry Federation (FEDIAF), for complete and balanced pet nutrition. Therefore, a nutritionally adequate diet is a diet with which said cat can be fed as the sole ration and is capable of sustaining life without additional food (except water).

[0083] The term "ppm" or “parts per million” is herein used according to its conventional meaning. More precisely, it refers herein to a weight amount relative to the total weight of the dry matter of the food composition (e.g., mg / kg) (unless otherwise indicated).

[0084] As used herein the term “providing” includes selling, supplying, administering, or feeding a cat.

[0085] As used herein, the term “weight percent” or “wt%” or “by weight” is meant to refer to the quantity by weight of a nutriment or ingredient in a food composition as a percentage on a dry matter basis of the food composition, unless otherwise specified. The specified amount of nutriments or ingredients included in a food composition as described herein represents the amount present in the total quantity of raw materials provided as sources of said nutriments or ingredients for producing the said food composition.

[0086] The expression “dry matter basis” or “DM” must be interpreted as a method of expressing the concentration of a nutrient or an ingredient in a food composition by expressing its concentration relative to its dry matter content (the concentration remaining once the moisture has been taken out). At the opposite, the expression “as fed” must be interpreted as a method of expressing the concentration of a nutrient or an ingredient in a food composition by expressing its concentration in the state it is fed, which includes moisture. It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable sub-combination.

[0087] As used herein, the terms “treating” or “treatment” in the present disclosure refers to the administration of a food composition according to the disclosure with the purpose to treat, alleviate, relieve, alter, remedy, ameliorate, improve, or affect chronic kidney disease, the symptoms of chronic kidney disease, the likelihood of chronic kidney disease, or to prevent or delay the onset of the symptoms, complications, or otherwise arrest or inhibit further development of chronic kidney disease in a statistically significant manner. More particularly, “treating” or “treatment” encompasses any approach for obtaining beneficial or desired results in a cat afflicted with chronic kidney disease. Beneficial or desired clinical results can encompass, but are not limited to, alleviation or amelioration of one or more symptoms or conditions associated with chronic kidney disease; diminishment or reduction of the severity of chronic kidney disease or symptoms related to chronic kidney disease; maintaining the stability (preventing deterioration) of chronic kidney disease; delaying or slowing down the progression of chronic kidney disease; minimizing the recurrence of chronic kidney disease; and remission, whether partial or total and whether detectable or undetectable. In other words, “treatment” as used herein includes any cure, amelioration, or reduction of chronic kidney disease or related symptom. A “reduction” of chronic kidney disease a symptoms of chronic kidney disease means decreasing of the severity or frequency of chronic kidney disease or symptoms of chronic kidney, or elimination of chronic kidney disease or symptoms of chronic kidney.

[0088] As used herein, the expression "delaying the progression" refers to the act of prolonging, preventing, slowing, postponing, stabilizing, or retarding the onset of chronic kidney disease or chronic kidney disease associated-symptoms. The duration of this delay can vary depending on the severity of chronic kidney disease being treated and the cat's medical history. A substantial or meaningful delay can effectively encompass prevention, whereby the individual does not develop chronic kidney disease. For instance, in the case of chronic kidney disease with the formation of crystal nanoparticle in the blood, it may be possible to delay its occurrence.

[0089] As used herein, the terms “prevent” or “preventing” (and grammatical variants thereof) with respect to chronic kidney disease relate to prophylactic treatment of chronic kidney disease, e.g., in a cat suspected to have chronic kidney disease, or at risk for developing chronic kidney disease. Prevention may include, but is not limited to, preventing, or delaying onset or progression of chronic kidney disease and / or maintaining one or more symptoms of chronic kidney disease at a desired or sub- pathological level. The term “prevent” does not require the 100% elimination of the possibility or likelihood of occurrence of the event. Rather, it denotes that the likelihood of the occurrence of the event has been reduced in the presence of a composition or method as described herein. More particular, “prevent” or “preventing” refers to a decrease in the risk of occurrence of chronic kidney disease or symptoms thereof in a cat. As indicated above, the prevention may be complete, i.e., no detectable symptoms or disease, or partial, such that fewer symptoms or less severity of chronic kidney disease are observed than would likely occur absent treatment.

[0090] As used herein, the term “phosphorus” refers to the chemical element with the symbol P and atomic number 15 in the periodic table. The term “phosphorus” can encompass “organic phosphorus” and “inorganic phosphorus”. The most prevalent compounds composed of phosphorus can be phosphates or derivatives of phosphates, such as pyrophosphates or tripolyphosphates. A phosphorus molecule has a molecular weight of 30.973761 g / mol.

[0091] As used herein, the term “phosphate” or “monophosphate” refers to an anion, salt, functional group or ester derived from a phosphoric acid, having the formula H3PO4. A phosphate is composed of oxygen (O), phosphorus (P), and eventually, one or two hydrogen (H). In the context of the present disclosure, a phosphate can refer to a phosphate having the formula [PC>4]3’. A phosphate can originate from either an organic source or an inorganic source. Inorganic phosphate being a free phosphate anion in solution. Organic phosphate being found in biological systems as a part of the structural material of bone, tissues, and teeth. A phosphate or a phosphate derivate can be a source of phosphorus. A source of phosphate can be one or more phosphate salt. A phosphate salt can be selected from a list comprising, but is not limited to, monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, calcium phosphate, ferric phosphate, magnesium phosphate, and ammonium phosphate.

[0092] As used herein, a “monopotassium phosphate” or “MKP” refers to an inorganic compound with the formula KH2PO4. The CAS number of MKP being 7778-77-0.

[0093] As used herein, the term “pyrophosphate” or “diphosphate” refers to the anion derived from phosphoric acid and having the formula P2O74’. Pyrophosphate refers to an inorganic pyrophosphate, also called PPi. In some embodiment, an inorganic pyrophosphate is typically introduced in a food composition as described herein as a food additive, specifically for increasing the attractiveness and / or the palatability of a food composition for a cat. In some embodiments, an inorganic pyrophosphate can be the food additive E450. In some embodiments, an inorganic pyrophosphate consists of a pyrophosphate salt.

[0094] As used herein, “a pyrophosphate salt” refers to an inorganic compound containing the pyrophosphate anion (P2O?4combined with a cation. In some embodiments, a pyrophosphate salt can be selected from the list, but is not limited to, sodium diphosphate, potassium diphosphate, calcium diphosphate, disodium dihydrogen diphosphate, trisodium diphosphate, tetrasodium diphosphate, and tetrapotassium diphosphate.

[0095] As used herein, a “cation” refers to an ion with a positive electric charge. It is formed when an atom or molecule loses one or more electrons. An atom or molecule which could be a cation can be selected in the list comprising ammonium, calcium, iron, magnesium, potassium, pyridinium, sodium, zinc, aluminum, and copper. It is intended that such atoms or molecules can encompass combination of two or more of such atoms or molecules. For instance, sodium can encompass sodium but also disodium, trisodium, tetrasodium, pentasodium, hexasodium, etc.

[0096] As used herein, a “cat” refers to a small mammal animal from the Felidae family. A cat can refer to a wild cat or a domestic cat. In some embodiments, a cat refers to a domestic cat or house cat. In some embodiments, a cat in need thereof refers to a cat suffering from chronic kidney disease.

[0097] It should be understood that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

[0098] All lists of items, such as, for example, lists of ingredients, are intended to and should be interpreted as Markush groups. Thus, all lists can be read and interpreted as items “selected from the group consisting of’ the list of items “and combinations and mixtures thereof.”

[0099] Units

[0100] As used herein, an amount of a nutrient or an ingredient as expressed as weight per megacalories, such as grams per megacalorie (g / Mcal), consists of a weight amount of the said nutrient or ingredient by unit of Metabolizable Energy (ME) of the food composition.

[0101] As used herein, the ME parameter is intended to represent the energy value of a food composition that is directly metabolized after consumption. Within the scope of the present disclosure, the ME value can be measured by any suitable method known in the art.

[0102] Illustratively, the ME value can be measured using feeding trial. In practice, the gross energy (GE) of the food composition is determined in the laboratory, and the amounts of food eaten by the animals are recorded. The feces and urine from the animals are collected, and the energy in each is determined and called fecal energy (FE) and urinary energy (UE), respectively. The ME is then calculated as:

[0103] ME (kcal / kg) = [GE - (FE + UE)] / Kg of food consumed.

[0104] Alternatively, the ME value can be measured by standard mathematical methods, taking into account, depending on the method, the percentage of crude fat (CF), of crude protein (CP), of NFE (carbohydrates) and / or of Total Dietary Fibers (TDF) in the food composition. In practice each percentage is multiplied by its respective Atwater Factors. The resulting sum is then multiplied by 10. The mathematical method can be represented by the following formula:

[0105] ME (kcal / kg) = 10 x [(3.5 x CP) + (8.5 x CF) + (3.5 x NFE)].

[0106] In some embodiments, the ME can be determined according to the predictive equation proposed by the National Research Council (NRC) in 2006.

[0107] In a particular embodiment of the disclosure, especially for a cat, the ME, in kcal / 100g, can be calculated as:

[0108] ME = GE x [95.6 - (0.89 x TDF x 100 / DM) ] / 100) - (0.77 x CP) or

[0109] ME = GE x [87.9 - (0.88 x CF x 100 / DM) ] / 100) - (0.77 x CP) with GE = (5.7 x CP) + (9.4 x CF) + [4.1 x (NFE + CF)]

[0110] In some embodiments, a food composition as disclosed herein can be characterized by its Metabolizable Energy (ME) parameter.

[0111] In some embodiments, a food composition as disclosed herein can have a Metabolizable Energy (ME) ranging from about 400 kcal / kg to about 5,000 kcal / kg, as measured according to the NRC 2006.

[0112] In some embodiments, mainly depending on its moisture content, a food composition as disclosed herein can have a Metabolizable Energy (ME) ranging from about 600 kcal / kg to about 4,000 kcal / kg or from about 1 ,000 kcal / kg to about 3,500 kcal / kg, or from about 2,000 kcal / kg to about 3,000 kcal / kg or from about 2,500 kcal / kg to about 2,900 kcal / kg, or from about 2,800 kcal / kg to about 2,900 kcal / kg, as measured according to the NRC 2006.

[0113] In some embodiments, a food composition as described herein can be a dry food composition, typically having a moisture content ranging from about 5% to about 12% by weight.

[0114] In some embodiments, a dry food composition as described herein can have a Metabolizable Energy (ME) ranging from about 3,000 kcal / kg to 5,000 kcal / kg, or from about 3,200 kcal / kg to about 4,800 kcal / kg, or from about 3,500 kcal / kg to about 4,000 kcal / kg or from about 3,800 kcal / kg to about 3,900 kcal / kg, as measured according to the NRC 2006.

[0115] In some embodiments, a dry food composition having a moisture content ranging from about 5% to about 12% by weight, can have a Metabolizable Energy (ME) ranging from about 3,000 kcal / kg to about 5,000 kcal / kg, or from about 3,200 kcal / kg to about 4,800 kcal / kg, or from about 3,500 kcal / kg to about 4,000 kcal / kg or from about 3,800 kcal / kg to about 3,900 kcal / kg, as measured according to the NRC 2006.

[0116] In some embodiments, a dry food composition as disclosed herein can have a Metabolizable Energy (ME) of about 3,000 kcal / kg, or about 3,100 kcal / kg, or about 3,200 kcal / kg, or about 3,300 kcal / kg, or about 3,400 kcal / kg, or about 3,500 kcal / kg, or about 3,600 kcal / kg, or about 3,700 kcal / kg, or about 3,800 kcal / kg, or about 3,900 kcal / kg, or about 4,000 kcal / kg, or about 4,100 kcal / kg, or about 4,200 kcal / kg, or about 4,300 kcal / kg, or about 4,400 kcal / kg, or about 4,500 kcal / kg, or about 4,600 kcal / kg, or about 4,700 kcal / kg, or about 4,800 kcal / kg, or about 4,900 kcal / kg or about 5,000 kcal / kg, as measured according to the NRC 2006.

[0117] In some embodiments, a dry food composition as described herein can have a Metabolizable Energy of about 3,400 kcal / kg, or about 3,450 kcal / kg, or about 3,500 kcal / kg, or about 3,550 kcal / kg, or about 3,600 kcal / kg, or about 3,650 kcal / kg, or about 3,700 kcal / kg, or about 3,750 kcal / kg, or about 3,800 kcal / kg, or about 3,850 kcal / kg, or about 3,900 kcal / kg, or about 3,950 kcal / kg or about 4,000 kcal / kg, as measured according to the NRC 2006.

[0118] In some embodiments, a dry food composition as described herein can have a Metabolizable Energy ranging from about 3,800 kcal / kg to about 3,900 kcal / kg, in particular about 3,850 kcal / kg, as measured according to the NRC 2006. In some embodiments, a dry food composition having a moisture content ranging from about 5% to about 12% by weight, can have a Metabolizable Energy ranging from about 3,800 kcal / kg to about 3,900 kcal / kg, in particular about 3,850 kcal / kg, as measured according to the NRC 2006.

[0119] In some embodiments, a food composition as described herein can be a wet food composition, typically having a moisture content ranging from about 50% to about 90% by weight.

[0120] In some embodiments, a wet food composition as described herein can have a Metabolizable Energy ranging from about 400 kcal / kg to about 1 ,600 kcal / kg, or from about 600 kcal / kg to about 1 ,400 kcal / kg, or from about 800 kcal / kg to about 1 ,200 kcal / kg, or from about 900 kcal / kg to about 1 ,000 kcal / kg as measured according to the NRC 2006.

[0121] In some embodiments, a wet food composition, having a moisture content ranging from about 50% to about 90% by weight, can have a Metabolizable Energy ranging from about 400 kcal / kg to about 1 ,600 kcal / kg, from about 600 kcal / kg to about 1 ,400 kcal / kg, from about 800 kcal / kg to about 1 ,200 kcal / kg, or from about 900 kcal / kg to about 1 ,000 kcal / kg as measured according to the NRC 2006.

[0122] In some embodiments, a wet food composition as described herein can have a Metabolizable Energy of about 400 kcal / kg, or about 450 kcal / kg, or about 500 kcal / kg, or about 550 kcal / kg, or about 600 kcal / kg, or about 650 kcal / kg, or about 700 kcal / kg, or about 750 kcal / kg, or about 800 kcal / kg, or about 850 kcal / kg, or about 900 kcal / kg, or about 950 kcal / kg, or about 1 ,000 kcal / kg, or about 1 ,050 kcal / kg, or about 1 ,100 kcal / kg, or about 1 , 150 kcal / kg, or about 1 ,200 kcal / kg, or about 1 ,250 kcal / kg, or about 1 ,350 kcal / kg or about 1 ,400 kcal / kg, or about 1 ,450 kcal / kg, or about 1 ,500 kcal / kg, or about 1 ,550 kcal / kg, or about 1 ,600 kcal / kg as measured according to the NRC 2006.

[0123] In some embodiments, a wet food composition as described herein can have a Metabolizable Energy of about 850 kcal / kg, or about 900 kcal / kg, or about 950 kcal / kg, or about 1000 kcal / kg, or about 1 ,050 kcal / kg, or about 1 ,100 kcal / kg, as measured according to the NRC 2006.

[0124] In some embodiments, a food composition as described herein can be a semi moist food composition, typically having a moisture content ranging from about 13% to about 49% by weight. In some embodiments, a semi-moist food composition as described herein can have a Metabolizable Energy ranging from about 1 ,600 kcal / kg to about 5,000 kcal / kg, as measured according to the NRC 2006.

[0125] In some embodiments, a semi-moist food composition, having a moisture content ranging from about 13% to about 49% by weight, can have a Metabolizable Energy ranging from about 1 ,600 kcal / kg to about 5,000 kcal / kg, as measured according to the NRC 2006.

[0126] In some embodiments, a semi-moist food composition as described herein can have a Metabolizable Energy of about 1 ,600 kcal / kg, or about 1 ,650 kcal / kg, or about 1 ,700 kcal / kg, or about 1 ,750 kcal / kg, or about 1 ,800 kcal / kg, or about 1 ,850 kcal / kg, or about 1 ,900 kcal / kg, or about 1 ,950 kcal / kg, or about 2,000 kcal / kg, or about 2,050 kcal / kg, or about 2,100 kcal / kg, or about 2,150 kcal / kg, or about 2,200 kcal / kg, or about 2,250 kcal / kg, or about 2,300 kcal / kg, or about 2,350 kcal / kg, or about 2,400 kcal / kg, or about 2,450 kcal / kg, or about 2,500 kcal / kg, or about 2,550 kcal / kg, or about 2,600 kcal / kg, or about 2,650 kcal / kg, or about 2,700 kcal / kg, or about 2,750 kcal / kg, or about 2,800 kcal / kg, or about 2,850 kcal / kg, or about 2,900 kcal / kg, 3,000 kcal / kg, or about 3,100 kcal / kg, or about 3,200 kcal / kg, or about 3,300 kcal / kg, or about 3,400 kcal / kg, or about 3,500 kcal / kg, or about 3,600 kcal / kg, or about 3,700 kcal / kg, or about 3,800 kcal / kg, or about 3,900 kcal / kg, or about 4,000 kcal / kg, or about 4,100 kcal / kg, or about 4,200 kcal / kg, or about 4,300 kcal / kg, or about 4,400 kcal / kg, or about 4,500 kcal / kg, or about 4,600 kcal / kg, or about 4,700 kcal / kg, or about 4,800 kcal / kg, or about 4,900 kcal / kg or about 5,000 kcal / kg, as measured according to the NRC 2006.

[0127] Chronic Kidney Disease

[0128] An object of the present disclosure relates to a food composition for use in a method for treating and / or delaying the progression and / or preventing of chronic kidney disease in a cat in need thereof.

[0129] In some embodiments, a food composition as described can be use in a method for treating chronic kidney disease in a cat in need thereof.

[0130] In some embodiments, a food composition as described can be use in a method for preventing chronic kidney disease in a cat.

[0131] In some embodiments, a food composition as described can be use in a method for delaying the progression of chronic kidney disease in a cat in need thereof. In cats, the kidneys are two blood-filtering organs located on the left and right in the retroperitoneal space. The two kidneys are part of the cat’s urinary system that further comprises two ureters, the bladder, and the urethra.

[0132] Kidneys contribute to controlling blood pressure, regulating blood circulation, producing hormones and enzymes, generating red blood cells, and removing toxins from the blood. Briefly, for the latter, the kidney receives blood from the paired renal arteries, the blood is filtered in the glomerulus through the nephrons, and then the filtered blood exits the kidney through the paired renal veins. The toxins removed from the blood are excreted via the ureter into the bladder through urine. A chronic kidney disease (CKD) can appear when the kidneys progressively loss their function.

[0133] In some embodiments, a kidney disease is characterized as chronic when signs or symptoms of the kidney disease are observed over a period of at least about 3 months. Symptoms occurring within a period of less than about 3 months are more indicative of acute kidney injury. An acute kidney injury can be qualifying as being chronic kidney disease when signs or symptoms of a kidney disease are observed in the cat after a continuous period of several months, typically at least about 3 months.

[0134] A chronic kidney disease affecting a cat can encompass various conditions that affect the kidneys.

[0135] In some embodiments, chronic kidney disease affecting a cat can involve the deterioration of renal parenchyma, the loss of functional nephrons, or the damage and / or the deterioration of the glomerulus.

[0136] The loss of functional nephrons can result from the formation of crystalline secondary nanoparticles when plasma phosphate concentration exceeds 3 mM in the S3 segment in the proximal tubule. Those crystalline secondary nanoparticles can be responsible for lysosomal dysfunction, inhibiting autophagy and predisposing to oxidative stress of the renal tubular cells, thus impairing renal function.

[0137] In some embodiments, chronic kidney disease affecting a cat can involve the loss of functional nephrons.

[0138] The renal parenchyma is divided into two major structures: the outer renal cortex, and the inner renal medulla. The structural alteration of renal parenchyma is mainly characterized by the expansion of renal fibrosis which results from the impairment of a regulated balance between pro- and anti-fibrotic factors.

[0139] In some embodiments, chronic kidney disease affecting a cat can result from an abnormal condition or a combination of one or more abnormal condition. In some embodiments, an abnormal condition of a cat potentially leading to chronic kidney disease can include cardiovascular diseases, cancer, hypertension, diabetes, glomerulonephritis, polycystic kidney diseases, ingestion of a toxic substance, obstructions by kidney-stones, advanced liver disease, genetic predisposition to the condition, old cats, high-phosphorus diets, high protein level diets and / or kidney graft rejection.

[0140] An old cat can be a cat over at least seven years old, eight years old, nine years old, ten years old, eleven years old, twelve years old, thirteen years old, fourteen years old, fifteen years old, sixteen years old, seventeen years old, eighteen years old, nineteen years old or twenty years old or more.

[0141] A toxic substance that can lead to chronic kidney disease in a cat can include antifreeze, pesticides, medications such as antibiotics or anti-inflammatory, and / or chemical detergents.

[0142] A kidney stone may be a calcium stone, a struvite stone, a uric acid stone and / or a cystine stone.

[0143] Generally, signs and symptoms of a cat indicating chronic kidney disease can be difficult to detect because some of the signs and symptoms of chronic kidney disease are similar to other cat troubles, such as diabetes or hyperthyroidism.

[0144] In some embodiments, chronic kidney disease can be observed or diagnosed through at least one or a combination of signs and / or symptoms.

[0145] In some embodiments, a sign and / or symptom indicating chronic kidney disease in a cat can include loss of appetite, increased thirst, frequent or absent urination, cloudy or bloody urine, vomiting, poor coat condition, lethargy, depression, weight loss, bad breath, mouth irritations / ulcerations, diarrhea, constipation, and / or increased sleep.

[0146] It is intended that a veterinarian can identify and diagnose signs and / or symptoms indicative of chronic kidney disease in a cat, and, if deemed necessary, confirm the diagnosis through additional tests.

[0147] Formulation of the food composition

[0148] The food composition as described herein includes a tripolyphosphate salt, as a source of inorganic phosphorus, to be used for treating and / or delaying the progression and / or preventing of chronic kidney disease in a cat in need thereof. In some embodiments, a food composition as described herein includes an effective amount of one or more tripolyphosphate salt as a source of inorganic phosphorus.

[0149] As used herein the term “tripolyphosphate salt”, refers to an inorganic compound containing the tripolyphosphate anion (PsO5’) combined with a cation, in particular a metal cation. In some embodiments, a tripolyphosphate salt can be chemically produced by a method of producing tripolyphosphate salt including at least a step of reacting of a cation, for instance potassium or sodium, with a tripolyphosphate anion.

[0150] In the present disclosure, a food composition as described herein can be formulated to include an effective amount of one or more tripolyphosphate salt, as a source of inorganic phosphorus, to reach a level of from about 0.1 g / Mcal to about 1.5 g / Mcal of inorganic phosphorus.

[0151] Consequently, the amount of tripolyphosphate salt to prepare a food composition as described herein depends on the target amount of inorganic phosphorus to be included within the food composition. In particular, the amount of inorganic phosphorus in the food composition cannot be higher than about 1.5 g / Mcal.

[0152] Without wishing to be bound by any theory, it is believed that a food composition comprising an amount of in organic phosphorus higher than about 1.5 g / Mcal could potentially be highly toxic for a cat and can cause or increase renal dysfunction.

[0153] Thus, a food composition as described herein can include from about 0.1 g / Mcal to about 1.5 g / Mcal of inorganic phosphorus originating from one or more source of inorganic phosphorus, such as from a tripolyphosphate salt, an inorganic pyrophosphate or a monophosphate salt.

[0154] In some embodiments, a food composition as described herein, including an effective amount of tripolyphosphate salt, can include about 0.1 g / Mcal, or about 0.2 g / Mcal, or about 0.3 g / Mcal, or about 0.4 g / Mcal, or about 0.5 g / Mcal, or about 0.6 g / Mcal, or about 0.7 g / Mcal, or about 0.8 g / Mcal, or about 0.9 g / Mcal, or about 1.0 g / Mcal, or about 1.1 g / Mcal, or about 1.2 g / Mcal, or about 1.3 g / Mcal, or about 1.4 g / Mcal, or about 1 .5 g / Mcal of inorganic phosphorus.

[0155] In some embodiments, a food composition as described herein, including an effective amount of tripolyphosphate salt, can include from about 0.1 g / Mcal to about 1.5 g / Mcal, or from about 0.5 g / Mcal to about 1.2 g / Mcal, or from about 0.5 g / Mcal to about 1.0 g / Mcal, or from about 0.8 g / Mcal to about 1.1 g / Mcal of inorganic phosphorus. In some embodiments, a food composition as described herein, including an effective amount of tripolyphosphate salt, can include about 1.0 g / Mcal or less, or about 0.9 g / Mcal or less, or about 0.8 g / Mcal or less, or about 0.7 g / Mcal or less, or about 0.6 g / Mcal, or less or about 0.5 g / Mcal or less, or about 0.6 g / Mcal or less, or about 0.5 g / Mcal or less, or about 0.4 g / Mcal or less, or about 0.3 g / Mcal or less, or about 0.2 g / Mcal or less, or about 0.1 g / Mcal or less of inorganic phosphorus.

[0156] It is believed that an amount of about 1.0 g / Mcal or less of inorganic phosphorus in the formulation of a food composition is safe for the cat and can contribute to the preventive and curative effect described in the present disclosure.

[0157] In some embodiments, a source of inorganic phosphorus can be a monophosphate salt, an inorganic pyrophosphate and / or a tripolyphosphate salt.

[0158] Illustratively, a source of inorganic phosphorus can be selected from the list comprising, but is not limited to, disodium phosphate, trisodium phosphate, tetrasodium phosphate, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, monocalcium phosphate, dicalcium phosphate, tricalcium phosphate, magnesium phosphate, monosodium phosphate, disodium pyrophosphate, tetrasodium pyrophosphate, dipotassium pyrophosphate, calcium pyrophosphate, pentasodium tripolyphosphate, dicalcium tripolyphosphate, sodium tripolyphosphate, potassium tripolyphosphate or a mix thereof.

[0159] In some embodiments, the inorganic phosphorus can originate from one or more inorganic pyrophosphate and one or more tripolyphosphate salt.

[0160] In some embodiments, a food composition as described herein can include at most about 0.5 g / Mcal of inorganic pyrophosphate.

[0161] In some embodiments, a food composition as described herein can include from about 0.1 g / Mcal to about 0.5 g / Mcal of inorganic pyrophosphate.

[0162] In some embodiments, a food composition as described herein can include about 0.1 g / Mcal, or about 0.2 g / Mcal, or about 0.3 g / Mcal, or about 0.4 g / Mcal or about 0.5 g / Mcal of inorganic pyrophosphate.

[0163] In some embodiments, the total amount of inorganic phosphorus can originate exclusively from one or more tripolyphosphate salt.

[0164] In some embodiments, a tripolyphosphate salt can be selected in the list comprising, but not limited to, sodium tripolyphosphate, potassium tripolyphosphate, ammonium tripolyphosphate, calcium tripolyphosphate, magnesium tripolyphosphate, zinc tripolyphosphate or a combination thereof. In some embodiments, a tripolyphosphate salt can be a sodium tripolyphosphate, a potassium tripolyphosphate or a combination thereof.

[0165] In some embodiments, a tripolyphosphate salt can be a potassium tripolyphosphate.

[0166] In some embodiments, a tripolyphosphate salt can be a sodium tripolyphosphate.

[0167] As used herein the term “sodium tripolyphosphate” or “STPP”, also called sodium triphosphate, refers to an inorganic compound composed of oxygen (O), phosphorus (P) and sodium (Na) and having the formula: NasPsO . Sodium tripolyphosphate is the sodium salt of the triphosphoric acid (H5P3O10) and thus composed of three phosphorus. Sodium tripolyphosphate is produced by heating a stoichiometric mixture of disodium phosphate (Na2HPC>4) and monosodium phosphate (NaH2PC>4) :2 Na2HPC>4 + NaH2PC>4 — ► NasPsO + 2 H2O. Sodium tripolyphosphate can be identified with the CAS Number 7758-29-4 or with the PubChem CID 517047. Sodium tripolyphosphate can be the food additive E451. Sodium tripolyphosphate has a molecular weight of 367.864 g / mol.

[0168] As used herein, the term "potassium tripolyphosphate" refers to an inorganic compound composed of oxygen (O), phosphorus (P), and potassium (K) with the chemical formula K5O10P3. Potassium tripolyphosphate is the potassium salt of triphosphoric acid and comprises three phosphorus atoms. It is produced by heating a stoichiometric mixture of dipotassium phosphate (K2HPO4) and monopotassium phosphate (KH2PO4). Potassium tripolyphosphate can be identified by its CAS Number 13845-36-8. Potassium tripolyphosphate has a molecular weight of 448.41 g / mol.

[0169] In some embodiments, sodium tripolyphosphate as a food additive can be chemically produced by a method of producing sodium tripolyphosphate including at least a step of reacting of a sodium compound with a phosphoric acid.

[0170] In some embodiments, a method of producing sodium tripolyphosphate can include at least the steps of

[0171] (a) reacting a sodium compound with a phosphoric acid, obtaining a mixture solution including monosodium phosphate and disodium phosphate,

[0172] (b) precipitating the mixture solution to a solid, and

[0173] (c) heating the mixture, obtaining sodium tripolyphosphate.

[0174] In some embodiments, a sodium compound can be a sodium carbonate and / or a sodium hydroxide. Step (b) can be essential to remove insoluble impurities from the mixture obtained at step (a) before processing step (c).

[0175] In some embodiments, the heating temperature at step (c) of a method of producing sodium tripolyphosphate can be performed under a temperature suitable to thermally decompose or calcinate the monosodium phosphate and the disodium phosphate into sodium tripolyphosphate.

[0176] In some embodiments, a method of producing sodium tripolyphosphate can further include a step (d) of grounding the heated mixture into a powder before storage.

[0177] In some embodiments, sodium tripolyphosphate can be a colorless salt.

[0178] In some embodiments, sodium tripolyphosphate can be a food additive.

[0179] Sodium tripolyphosphate can be a food additive chemically produced.

[0180] In some embodiments, sodium tripolyphosphate can be the food additive having the E number E451.

[0181] An E number, short for Europe number, is a code given within the European Union for identifying substances used as food additives and reported in the Regulation (EC) No 1333 / 2008 of the European Parliament and of the Council of 16 December 2008 on food additives.

[0182] For instance, the food additive E451 can be purchased from Thermo Scientific Chemicals.

[0183] It is intended that a skilled person in the art has the competence to ascertain the adequate amount of source of inorganic phosphorus, such as a tripolyphosphate salt, to incorporate into the food composition based on the target amount of inorganic phosphorus. This can be achieved by calculating the weight of the one or more phosphorus salt based on its molecular weight as well as the molecular weight of phosphorus.

[0184] Illustratively, to determine the phosphorus salt amount to be included in a food composition to reach a target level of inorganic phosphorus, it can be achieved the following steps:

[0185] (a) determining the percentage of phosphorus in the salt according to the formula: [Molecular weight of total phosphorus of the salt] I [Total molecular weight of the salt] = percentage of phosphorus in the salt, and

[0186] (b) determining the weight of the salt within the food composition according to the formula: [Target weight (g / Mcal) of inorganic phosphorus] I [percentage of phosphorus in the salt] = Weight (g / Mcal) of the salt. Illustratively, a skilled person wanted to incorporate 1.0 g / Mcal of inorganic phosphorus from sodium tripolyphosphate within a food composition having a Metabolizable Energy of 3,900 kcal / kg, it can be determined the weight amount of sodium tripolyphosphate by multiply the target level of inorganic phosphorus by a factor of about 3.95, to obtain the approximated weight amount of sodium tripolyphosphate. Otherwise say, a food composition as described herein, having a Metabolizable Energy of about 3,900 kcal / kg, with about 1.0 g / Mcal of inorganic phosphorus from sodium tripolyphosphate, can include about 3.95 g / Mcal of sodium tripolyphosphate.

[0187] Thus, as stated in the present disclosure, it is intended that the weight amount of tripolyphosphate salt to incorporate in a food composition mainly depend on the target amount of inorganic phosphorus to be comprised in the food composition, the molecular weight of the salt and the Metabolizable Energy (ME) of the food composition.

[0188] In some illustrative embodiments, a food composition as described herein, can include, as an effective amount, from about 0.3 g / Mcal to about 6.0 g / Mcal, or from about 2 g / Mcal to about 5 g / Mcal, or from about 2.5 g / Mcal to about 4.5 g / Mcal, or from about 3.5 g / Mcal to about 4.2 g / Mcal of sodium tripolyphosphate.

[0189] In some illustrative embodiments, a food composition as described herein, can include, as an effective amount, about 0.3 g / Mcal, or about 0.4 g / Mcal or about 0.6 g / Mcal, or about 0.9 g / Mcal, or about 1.2 g / Mcal, or about 1.5 g / Mcal, or about 1.8 g / Mcal, or about 2.1 g / Mcal, or about 2.4 g / Mcal, or about 2.7 g / Mcal, or about 3.0 g / Mcal, or about 3.3 g / Mcal, or about 3.6 g / Mcal, or about 3.9 g / Mcal, or about 3.95 g / Mcal, or about 4.2 g / Mcal, or about 4.5 g / Mcal, or about 4.8 g / Mcal, or about 5.1 g / Mcal, or about 5.4 g / Mcal, or about 5.7 g / Mcal, or about 5.9 g / Mcal or about 6.0 g / Mcal of sodium tripolyphosphate.

[0190] Generally, a tripolyphosphate salt, as a source of inorganic phosphorus, can be categorized as a source of minerals, also called ash, within the nutritional aspect of a food composition.

[0191] As used herein, “ash” refers to any inorganic material present in a food composition. Ash content in food compositions typically comes from various ingredients. Ash is essentially the mineral content left behind after organic matter has been burned off during analysis. The ash content, if specified, results from an analytical measure of a food composition which is a measure of the total amount of minerals comprised therein. The mineral content is a measure of the amount of specific inorganic nutriment comprised therein, which includes calcium (Ca), sodium (Na), potassium (K) and chlorine (Cl).

[0192] In some embodiments, ash can include minerals. For instance, mineral nutriments can encompass calcium, phosphorus, sodium, chloride, potassium, magnesium, or combinations thereof.

[0193] In the present disclosure, a tripolyphosphate salt can be a source of ash for both phosphorus and the cation of the salt. The present disclosure also encompasses the incorporation of one or more other sources of ash into the food composition as described herein, aimed at further providing calcium, sodium, chloride, potassium, and / or magnesium content.

[0194] In some embodiments, a source of ash that can be included in a food composition as described herein can encompass meat; fish; bone meal; poultry byproducts; fish meal; eggshells; grains such as rice, wheat; mineral supplements, or combination thereof.

[0195] Mineral supplements can encompass calcium carbonate, potassium chloride, dicalcium phosphate, tripolyphosphate salt, pyrophosphate salt, phosphate salt, or combination thereof.

[0196] Typically, a source of ash in a raw material, such as meat, can also provide to the food composition a source of water, a source of fat, a source of fibers, a source of proteins and / or a source of vitamins. The nutritional composition of the source of ash depending on the quality and the specificity of the raw material.

[0197] In some embodiments, the food composition as described herein can include ash, wherein the content of ash can include calcium, phosphorus, sodium, chloride, potassium, magnesium or combinations thereof.

[0198] In some embodiments, the food composition as described herein can include ash, wherein the content of ash can include calcium, phosphorus, sodium, potassium, magnesium or combinations thereof.

[0199] In some embodiments, the food composition as described herein can include ash, wherein the content of ash can include calcium, phosphorus, sodium, potassium, or combinations thereof. In some embodiments, the food composition as described herein can include, on a dry matter basis, from about 6% to about 14%, or from about 7% to about 13%, or from about 8% to about 12% or from about 9% to about 11 % by weight of ash.

[0200] In some embodiments, the food composition as described herein can include, on a dry matter basis, about 6%, or about 6,5% or about 7%, or about 7,5%, or about 8%, or about 8,5%, or about 9%, or about 9,5%, or about 10%, or about 10,5%, or about 11 %, or about 11 ,5%, or about 12%, or about 12,5%, or about 13%, or about 13,5%, or about 14% by weight of ash.

[0201] In some embodiments, a food composition as described herein can include from about 0.4 g / Mcal to about 7 g / Mcal of phosphorus, or about 0.5 g / Mcal to about 7 g / Mcal of phosphorus.

[0202] In some embodiments, a food composition as described herein can include about 0.4 g / Mcal, or about 0.5 g / Mcal, or about 0.6 g / Mcal, or about 0.7 g / Mcal, or about 0.8 g / Mcal, or about 0.9 g / Mcal, or about 1 g / Mcal, or about 1.5 g / Mcal, or about 2 g / Mcal, or about 2.5 g / Mcal, or about 3 g / Mcal, or about 3.5 g / Mcal, or about 4 g / Mcal, or about 4.5 g / Mcal, or about 5 g / Mcal, or about 5.5 g / Mcal, or about 6 g / Mcal, or about 6.5 g / Mcal, or about 7 g / Mcal of phosphorus.

[0203] Phosphorus encompasses the total content of organic phosphorus and inorganic phosphorus.

[0204] As previously stated, a food composition as described herein can include calcium as a part of ash.

[0205] In some embodiments, a source of calcium to be provided in a food composition as described herein can encompass meat, fish, bone meal, fish bones, eggshells, dairy products, mineral supplements, ground limestone.

[0206] A mineral supplement as a source of calcium can encompass calcium carbonate, calcium citrate, calcium propionate, calcium lactate and / or calcium gluconate.

[0207] Typically, a source of calcium in a raw material, such as meat, can also provide to the food composition a source of water, a source of fat, a source of fibers, a source of proteins, a source of other ash and / or a source of vitamins. The nutritional composition of the source of ash depending on the quality and the specificity of the raw material. In some embodiments, a food composition as described herein can include calcium and phosphorus such that the weight ratio of calcium to phosphorus can be characterized by being equal or higher than about 1.

[0208] In some embodiments, a food composition as described herein can include calcium and phosphorus such that the weight ratio of calcium to phosphorus can be characterized by being from 1 to 2, or from 1.1 to 1.9, of from 1.2 to 1.8, or from 1.2 to 1.6, or from 1.2 to 1.4.

[0209] In some particular embodiments, a food composition as described herein can include calcium and phosphorus such that the weight ratio of calcium to phosphorus can be characterized by being equal of about 1 , 1.1 , 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2.

[0210] Illustratively, a food composition as described herein can include calcium and phosphorus such that the weight ratio of calcium to phosphorus can be characterized by being from 1.2 to 1.4.

[0211] In some embodiments, a food composition as described herein can include from about 1 g / Mcal to about 7 g / Mcal of calcium.

[0212] In some embodiments, the food composition as described can include about 1 g / Mcal, or about 1.5 g / Mcal, or about 2 g / Mcal, or about 2.5 g / Mcal, or about 3 g / Mcal, or about 3.5 g / Mcal, or about 4 g / Mcal, or about 4.5 g / Mcal, or about 5 g / Mcal, or about 5.5 g / Mcal, or about 6 g / Mcal, or about 6.5 g / Mcal, or about 7 g / Mcal of calcium.

[0213] Illustratively, a food composition as described herein can include from about 1 g / Mcal to about 3 g / Mcal of calcium, specifically from about 1.2 g / Mcal to about 2 g / Mcal, or from about 1.4 g / Mcal to about 1.8 g / Mcal, more specifically of about 1.4 g / Mcal, or about 1 .5 g / Mcal, or about 1 .6 g / Mcal, or about 1.7 g / Mcal of calcium.

[0214] As previously stated, a food composition as described herein can include potassium as a part of ash.

[0215] In some embodiments, a source of potassium to be provided in a food composition as described herein can encompass, but is not limited to, meat, vegetal, potassium citrate, potassium chloride or a mixture thereof.

[0216] Meat, as a source of potassium, can encompass, but is not limited to, chicken, turkey, beef, or fish. These animal protein sources naturally contain potassium. Vegetal, as a source of potassium, can encompass, but is not limited to, sweet potatoes, spinach, carrots or beets.

[0217] Typically, a source of potassium from a raw material, such as meat, can also provide to the food composition a source of water, a source of fat, a source of fibers, a source of proteins, a source of other ash and / or a source of vitamins. The nutritional composition of the source of potassium depending on the quality and the specificity of the raw material.

[0218] In some embodiments, a food composition as described herein can include from about 1 g / Mcal to about 4.5 g / Mcal of potassium, or about 1.1 g / Mcal to about 4.2 g / Mcal of potassium, or about 1 .3 g / Mcal to about 4.1 g / Mcal of potassium, or about 1 .5 g / Mcal to about 3.8 g / Mcal of potassium, or about 1 .7 g / Mcal to about 3.5 g / Mcal of potassium.

[0219] In some embodiments, the food composition as described can include 1.0 g / Mcal, or about 1.1 g / Mcal, or about 1.2 g / Mcal, or about 1.3 g / Mcal, or about 1.4 g / Mcal, or about 1.5 g / Mcal, or about 1.6 g / Mcal, or about 1.7 g / Mcal, or about 1.8 g / Mcal, or about 1.9 g / Mcal, or about 2 g / Mcal, or about 2.1 g / Mcal, or about 2.2 g / Mcal, or about 2.3 g / Mcal, or about 2.4 g / Mcal, or about 2.5 g / Mcal, or about 2.6 g / Mcal, or about 2.7 g / Mcal, or about 2.8 g / Mcal, or about 2.9 g / Mcal, or about 3 g / Mcal, or about 3.1 g / Mcal, or about 3.2 g / Mcal, or about 3.3 g / Mcal, or about 3.4 g / Mcal, or about 3.5 g / Mcal, or about 3.6 g / Mcal, or about 3.7 g / Mcal, or about 3.8 g / Mcal, or about 3.9 g / Mcal or about 4 g / Mcal, or about 4.1 g / Mcal, or about 4.2 g / Mcal, or about 4.3 g / Mcal, or about 4.4 g / Mcal, or about 4.5 g / Mcal of potassium.

[0220] In some embodiments, the food composition as described herein can include other nutrients and / or ingredients.

[0221] In some embodiments, the food composition as described herein can further include, but is not limited to, protein, fat, fibers and / or vitamins.

[0222] In some embodiments, the food composition as described herein can include proteins, flavors, preservatives, trace elements, coloring, fats, fibers, and / or vitamins. Notably, in such embodiments, these proteins, flavors, preservatives, trace elements, coloring, fats, fibers, and / or vitamins are supplementary or in complement to the ash content incorporated into the food composition as previously described. Accordingly, the amount of the other nutrients and / or ingredients shall be present in an adequate amount to ensure maintenance of lean body mass of the cat while no being toxic for the cat.

[0223] In some embodiments, the food composition as described herein can include proteins.

[0224] Accordingly, the protein level shall be high enough to ensure maintenance of lean body mass of the cat while no being toxic for the cat.

[0225] In some embodiments, a food composition as described herein can include, on a dry matter basis, from about 20% to about 50% by weight of protein.

[0226] In some embodiments, a food composition as described herein can include, on a dry matter basis, from about 20%, or about 21 %, or about 22%, or about 23%, or about 24%, or about 25%, or about 26%, or about 27%, or about 28%, or about 29%, or about 30%, or about 31 %, or about 32%, or about 33%, or about 34%, or about 35%, or about 36%, or about 37%, or about 38%, or about 39%, or about 40%, or about 41 %, or about 42%, or about 43%, or about 44%, or about 45%, or about 46%, or about 47%, or about 48%, or about 49%, or about 50% by weight of protein.

[0227] Illustratively, a food composition as described herein can include, on a dry matter basis, from about 20% to about 35%, or from about 20% to about 30%, or from about 20% to about 28% by weight of protein.

[0228] In some embodiments, a food composition as described herein can include a plurality of source of proteins.

[0229] In some embodiments, the proteins can be non-hydrolyzed protein.

[0230] In some embodiments, the proteins can be hydrolyzed protein.

[0231] An ingredient that can be a protein source for the manufacture of a food composition as described herein can originate from an animal protein source and / or a vegetal protein source. Notably, an animal protein source and / or a vegetal protein source can be a raw material.

[0232] In some embodiments, a protein source can be a mixture of one or more animal protein source or one or more vegetable protein source, or one or more animal and vegetal protein sources. In some embodiments, a protein source can be a mixture of at least one animal protein source.

[0233] A source of protein in a raw material can also provide to the food composition as described herein a source of water, a source of fat, a source of ash, a source of fibers, and / or a source of vitamins. The nutritional composition of the source of protein depending on the quality and the specificity of the raw material. For instance, an animal source of protein can also provide fats.

[0234] In some embodiments, an animal protein source can be selected from, but is not limited to, poultry, poultry meal, poultry by-product, lamb, lamb meals, pork, pork byproduct, beef, beef by-products, white fish, milk proteins, egg, venison or a combination thereof.

[0235] Poultry can encompass chicken, duck, turkey, geese, and quail.

[0236] A vegetable protein source can be selected, without limitation, from soybean meal, soy protein isolate, rice, soy protein concentrate, maize gluten, wheat gluten, gluten, tofu, green lentils, carrot, potato, beets, com gluten meal, com protein concentrate or a combination thereof.

[0237] Protein content of a food composition can be determined by any methods known by the person of skill in the art.

[0238] In some embodiments, the food composition as described herein can include fats.

[0239] In some embodiments, the food composition can include fats from an animal fat source and / or a vegetable fat source.

[0240] In some embodiments, a vegetable fat source can include, without limitation, wheat, soy, sunflower, safflower, rapeseed, olive, borage, flaxseed, peanuts, blackcurrant seed, cottonseed, wheat, germ, com germ as well as oils derived from these and combinations thereof.

[0241] In some embodiments, an animal fat source can include, without limitation, chicken crude fat, turkey crude fat, beef crude fat, duck crude fat, pork crude fat, lamb crude fat, fish oil or any meat, meat by-products, seafood, fish by-products, dairy, eggs or a combination thereof.

[0242] Fats can be supplied by any sources known by the person skilled in the art. In some embodiments, a food composition as described herein can include, on a dry matter basis, from about 5% to about 25% by weight of fat.

[0243] In some embodiments, a food composition as described herein can include, on a dry matter basis, or about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10%, or about 11 %, or about 12%, or about 13%, or about 14%, or about 15%, or about 16%, or about 17%, or about 18%, or about 19%, or about 20%, or about 21%, or about 22%, or about 23%, or about 24%, or about 25% by weight of fat.

[0244] In some embodiments, a food composition as described herein can include, on a dry matter basis, from about 5% to about 25%, particularly from about 10% to about 20% by weight of fat.

[0245] Illustratively, a food composition as described herein can include, on a dry matter basis, from about 12% to about 17% by weight of fat.

[0246] Fat content of a food composition as described herein can be determined by any methods known by the person of skill in the art.

[0247] In some embodiments, the food composition as described herein can include fibers.

[0248] As used herein fibers designates soluble fibers and insoluble fibers.

[0249] In some embodiments, the food composition as described herein can include, on a dry matter basis, from about 4% to about 15% by weight of fiber.

[0250] In some embodiments, the food composition as described herein can include, on a dry matter basis, about 4%, or about 4.5%, or about 5%, or about 5.5%, or about 6%, or about 6.5%, or about 7%, or about 7.5%, or about 8%, or about 8.5%, or about 9%, or about 9.5%, or about 10%, or about 10.5%, or about 11 %, or about 11.5%, or about 12%, or about 12.5%, or about 13%, or about 13.5%, or about 14%, or about 14.5%, or about 15% by weight of fiber.

[0251] Illustratively, a food composition as described herein can include, on a dry matter basis, from about 4% to about 10% by weight of fiber.

[0252] In some embodiments, a source of fibers can be selected from, but is not limited to, beet pulp, guar gum, chicory root, psyllium, pectin, blueberry, cranberry, squash, apples, oats, beans, citrus, barley, or peas cellulose, whole wheat products, wheat oat, corn bran, flax seed, grapes, celery, green beans, cauliflower, potato skins, fruit skins, vegetable skins, peanut hulls, soy fiber and a combination thereof.

[0253] Fiber’s content of a food composition as described herein can be determined by any methods known by the person of skill in the art.

[0254] In some embodiments, the food composition as described can also include preservatives, trace elements and / or coloring.

[0255] In some embodiments, a food composition as described herein can further include a diluent and / or an excipient.

[0256] A diluent can encompass water or broth or stock. Broth can generally be made by simmering meat, such as chicken, beef or fish, or vegetables in water. Stock can generally be made by simmering bones in water, and eventually with vegetables and / or meat.

[0257] An excipient can encompass antioxidants, flavors, prebiotics, probiotics or taurine.

[0258] Typically, a food composition as disclosed heroin can include tripolyphosphate salt and, optionally, one or more further ingredient, such as a source of protein, a source of ash, a source of fibers, a source of fat, additives and / or vitamins. The sum of the weight of each of the ingredients comprised therein amounting, on a dry matter basis, to 100% by weight.

[0259] Typically, a food composition as disclosed heroin can include several substances and / or nutriments such as protein, ash, fibers, fat, additives and / or vitamins. The sum of the weight of each of the substances and / or nutriments comprised therein amounting, on a dry matter basis, to 100% by weight.

[0260] Table 1 below provides an example of a food composition as described heroin for use in a method for treating and / or delaying the progression and / or preventing of chronic kidney disease in a cat in need thereof.

[0261] Table 1: Illustrative cat food composition in the form of a dry food for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof.

[0262] Food composition

[0263] The food composition as described herein including tripolyphosphate salt, as a source of inorganic phosphorus, can be a nutritionally complete and balanced food composition or a functional food.

[0264] As used herein, the term “functional complement” refers to a food composition which provides specific components that are important for health maintenance beyond basic nutrition. These food compositions can contain substances or ingredients that are biologically active or bioavailable, such as probiotics, amino acids, vitamins, minerals and antioxidants, and often are found to be useful for the treatment of diseases or the maintenance of normal health states. Functional complements are not nutritionally complete food compositions, meaning that a functional complement does not provide the complete and balanced nutritional requirements to a companion animal.

[0265] In some embodiments, a food composition as described herein can consist of a nutritionally complete and balanced food composition.

[0266] In some embodiments, a nutritionally complete and balanced food composition as described herein can comprise nutrients and / or ingredients that are formulated to contribute to the nutritional properties of the food composition. Illustratively, a nutritionally complete and balanced food composition as described herein can include, but is not limited to, protein, fat, ash, fibers, carbohydrates, starch, calcium, phosphorus, sodium, chloride, potassium, magnesium, iron, water, copper, manganese, zinc, taurine, selenium, flavouring, vitamin A, vitamin D3, vitamin B1 , vitamin B2, vitamin B6, vitamin B12, vitamin B7, vitamin B9, choline chloride, arachidonic acid, W3 fatty acid, W6 fatty acid or combinations thereof.

[0267] In some embodiments, a food composition as described herein can consist of a wet food composition, a dry food composition or a semi-moist food composition.

[0268] A dry food composition can refer to a food composition having a moisture content of less than about 12% by weight, relative to the total weight of the food composition.

[0269] A process for determining the moisture content of a food composition can comprises at least the steps of (i) selecting a representative sample of the food composition, (ii) weighing the sample, (iii) then subjecting the sample to complete dehydration in a temperature-controlled oven, typically around 100°C, until all water is evaporated, (iv) after cooling in a desiccator, weighing again the dehydrated sample. The moisture content is then calculated using the formula: Moisture Content (%) = [(Initial Mass - Mass after dehydration) I Initial Mass] x 100.

[0270] In some embodiments, a dry food composition as described herein can have a moisture content ranging from about 5% to about 12% by weight, relative to the total weight of the food composition.

[0271] In some embodiments, a dry food composition as described herein can have a moisture content of about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10%, or about 11%, or about 12% by weight, relative to the total weight of the food composition.

[0272] Typically, a dry food composition can have a moisture content of about 8% by weight, relative to the total weight of the food composition.

[0273] In some embodiments, a dry food composition can be formed by an extrusion process.

[0274] In some embodiments, a dry food composition can be formed from a core and a coating to form a dry food composition that is coated, also called a coated dry animal food composition.

[0275] In some embodiments, a dry food composition can be a kibble. A semi-moist food composition refers to a food composition having a moisture content ranging from about 13% to about 49 % by weight, relative to the total weight of the food composition.

[0276] T ypically, a semi-moist food composition is the final product of a process allowing a moisture content value that is intermediate between a dry food and a wet food. In some embodiments, the said process can comprise a step of adding a humectant agent. In some embodiments, the said process can comprise an extrusion step and a subsequent treatment step with Super-Heated Stream (SHS).

[0277] In some embodiments, a semi-moist food composition as described herein can have a moisture content of about 13%, or about 14%, or about 15%, or about 16%, or about 17% or about 18, or about 9%, or about 20% or about 21%, or about 22%, or about 23%, or about 24%, or about 25%, or about 26%, or about 27%, or about 28%, or about 29%, or about 30%, or about 31 %, or about 32%, or about 33%, or about 34%, or about 35%, or about 36%, or about 37%, or about 38%, or about 39%, or about 40%, or about 41 %, or about 42%, or about 43%, or about 44%, or about 45%, or about 46%, or about 47%, or about 48%, or about 49% by weight, relative to the total weight of the food composition.

[0278] In some embodiments, a semi-moist food composition as described herein can have a water activity of about 0.64 to about 0.75.

[0279] In certain embodiments, a semi-moist food composition can have a moisture content ranging from about 13% to about 49% by weight, relative to the total weight of the food composition, and preferably with a water activity of about 0.64 to about 0.75.

[0280] Water activity can be measured using a water activity (aw) meter.

[0281] Typically, a semi-moist food composition can have a moisture content of about 20% by weight, relative to the total weight of the food composition.

[0282] A wet food composition refers to a food composition having a moisture content of more than about 50% by weight, relative to the total weight of the food composition.

[0283] In some embodiments, a wet food composition refers to a food composition having a moisture content ranging from about 50% to about 90% by weight, relative to the total weight of the food composition.

[0284] In some embodiments, a wet food composition as described herein can have a moisture content of about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90% by weight, relative to the total weight of the food composition. Typically, a wet food composition can have a moisture content of about 80% by weight, relative to the total weight of the food composition.

[0285] In general, a wet food composition is the final product of a process including a final step of sterilization (instead of a drying step).

[0286] In some embodiments, a wet food composition can consist of a chunk form, more particularly of chunks in gravy form.

[0287] In some embodiments, a wet food composition can consist of chunks and gravy, chunks in jelly, loaf, mousse, terrine or bites form.

[0288] In some particular embodiments, a food composition as described herein can consist of a dry food composition.

[0289] Uses and methods

[0290] An object of the present disclosure relates to a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof.

[0291] An object of the present disclosure also relates to a food composition as described herein comprising an effective amount of tripolyphosphate salt, as a source of inorganic phosphorus, for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof.

[0292] Another aspect of the present disclosure relates to a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof comprising at least the step of feeding the cat with a food composition as described herein.

[0293] In some embodiments, treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, consisting of treating and / or delaying the progression of and / or preventing signs and symptoms of chronic kidney disease.

[0294] In some embodiments, treating and / or delaying the progression of and / or preventing signs and symptoms of chronic kidney disease in a cat can consist of treating and / or delaying the progression of and / or preventing a loss of appetite, an increased thirst, a frequent or absent urination, a cloudy or bloody urine, vomiting, a poor coat condition, a lethargy, a depression, a weight loss, a bad breath, mouth irritations / ulcerations, a diarrhea, a constipation, and / or an increased sleep of the cat.

[0295] In some embodiments, treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat can encompass treating and / or delaying the progression of and / or preventing of the deterioration of renal parenchyma, the loss of functional nephrons, or the damage and / or the deterioration of the glomerulus in the cat.

[0296] In some embodiments, a cat can be considered as suffering from chronic kidney disease when the frequency of the signs and symptoms as described herein by the cat occurs at least 2 times per week or more, or 3 times per week or more, or 4 times per week or more, or 5 times a week or more, or 6 times a week or more, or every day in a week over a period of at least 3 months or more, or 4 months or more, or 5 months or more, or 6 months or more, or 7 months or more, or 8 months or more, or 9 months or more, or 10 months or more, or 11 months or more, or 12 months or more.

[0297] In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated to be administered to the cat daily as part of its diet.

[0298] In the field of pet nutrition, it is well-established that those skilled in the art possess the knowledge and expertise to adapt the formulation of a food composition to align with specific feeding recommendations for the target animal. For instance, if the recommendation specifies that a cat should be fed once a day, twice a day, and / or only on specific days of the week, the skilled person can readily modify the food composition accordingly. In particular, the skilled person can readily modify the formula of the food composition accordingly to provide a food composition having an effective amount of tripolyphosphate salt as defined herein.

[0299] In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated to be provided to the cat in need thereof in alternation with another food composition.

[0300] In some embodiments, the said another food composition can be another nutritionally complete and balanced food composition. In particular, the another food composition can be selected from food compositions in the art, including the large variety of commercialized food compositions adapted to the cat.

[0301] In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, wherein the food composition as described herein can be formulated to be provided to the cat in need thereof every other day, with said another food composition being provided on alternate days.

[0302] In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated to be provided to the cat in need thereof from several weeks to several years, depending notably on the severity of the chronic kidney disease.

[0303] In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated to be suitable to be provided to the cat in need thereof on a daily basis every day in a week over a period of at least 3 months or more, or 4 months or more, or 5 months or more, or 6 months or more, or 7 months or more, or 8 months or more, or 9 months or more, or 10 months or more, or 11 months or more, or 12 months or more.

[0304] In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated to be provided to a cat in need thereof during a longer period of time, such as during 12 months or more, or 18 months of more, or 24 months or more, either (i) according to a feeding schedule wherein the cat exclusively fed the food composition as described herein or (ii) according to a feeding schedule wherein the cat alternating the food composition described herein and another corresponding dry food composition.

[0305] In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated to be provided to the cat in need thereof on a daily basis every day in a week over the whole lifetime of the cat. In some embodiments, a food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated to be provided to the cat in need thereof on a daily basis every day in a week over the whole lifetime of the cat, alternating with another food composition.

[0306] A food composition as described herein for use in a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof, can be formulated in such a manner that the body weight of the cat is not significantly affected.

[0307] In some embodiments, a method for treating and / or delaying the progression of and / or preventing chronic kidney disease in a cat in need thereof further comprises a step of making a feeding recommendation that includes a food composition as described herein.

[0308] Without wishing to be bound by any particular theory, an efficient treatment and / or delay of the progression of chronic kidney disease in a cat can occur when there is an improvement in one or more of the signs and symptoms associated with chronic kidney disease.

[0309] Method of manufacturing

[0310] The present disclosure also relates to a method of manufacturing a food composition for a cat as described herein including at least a step of mixing all the ingredients together.

[0311] The food composition as described herein can be prepared according to the techniques which are well known to a person skilled in the art.

[0312] EXAMPLES

[0313] This disclosure can be further illustrated by the following examples of particular embodiments thereof, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the disclosure.

[0314] Inorganic phosphorus may be highly detrimental for cats with renal disease. The following examples demonstrate that the use of a tripolyphosphate salt, a source of inorganic phosphorus, allows to raise the level of plasma pyrophosphate in the blood of a population of cats (Figures 1 and 2) while limiting the level of plasma phosphorus (Figure 3).

[0315] Raising the levels of pyrophosphate in the blood can be a solution to treat, or delay the progression, of kidney disease in cats suffering from a chronic kidney disease.

[0316] Abbreviations

[0317] AUC : Area under the curve

[0318] BUN : blood urea nitrogen

[0319] BSC : Body score condition

[0320] CKD : Chronic kidney disease

[0321] CBC : complete blood count

[0322] Kg: kilogram

[0323] MKP: monopotassium phosphate

[0324] Pi: inorganic phosphorus

[0325] P: Organic phosphorus

[0326] PPi: inorganic pyrophosphate

[0327] PTH: parathyroid hormone

[0328] STPP : Sodium tripolyphosphate

[0329] SDMA : Symmetrical Dimethylarginine USG : Urine specific gravity g: gram g / Mcal : gram per megacalories

[0330] A. Material & Methods a. Population of cats The pharmacokinetics of (i) a mix of 50% by weight of potassium monophosphate and 50% by weight of inorganic pyrophosphate and (ii) Sodium tripolyphosphate (STTP) was studied in a population of healthy cats according to the protocol as described by Coltherd et al. British Journal of Nutrition 2019; 121 (3):270- 284.

[0331] In this assay, 28 different healthy cats were enrolled.

[0332] The selection of the cats followed inclusion and non-inclusion criteria, as well as exclusion criteria during the trial. *Cat stress score from Kessler & Turner (1997), Animal Welfare, 6(3), 243-254. : 1. Fully relaxed; 2. Weakly relaxed; 3. Weakly tense; 4. Very Tense; 5. Fearful, Still; 6. Very Fearful; 7. Terrified. b. Trial All cats were fed with a maintenance food composition in amounts required to maintain an ideal body weight of the cats (BCS of 5), at least seven days before getting the tested food compositions (Diet A or B).

[0333] On the collection day, a baseline blood sample (1 mL) was taken from cats before the meal to measure serum pyrophosphate concentration. Then, blood samples were collected from cats 60 minutes after they were fed the food composition (1 mL of blood).

[0334] Serum pyrophosphate concentration was examined to assess the absorption of intact pyrophosphate. Serum inorganic pyrophosphate concentration was determined using a fluorometric assay kit (ab112155, Abeam®, Cambridge, MA, CA).

[0335] Blood sample was collected from cats in tubes containing heparin (5 USP units / mL of blood). Subsequently, blood samples were kept at 4°C for a maximum of 6 hours. Then, the blood samples are centrifugated (3,000 rpm for 10 minutes at 4°C) and serum is recovered. Serum samples are subsequently stored at -80°C until measurement of the pyrophosphate concentration. For the pyrophosphate concentration analysis, 300pL of serum was applied to 10-kDa (kilodalton) cutoff ultrafiltration spin columns (ab93349, abeam®, Cambridge) and sedimented at 14,000g for 20 minutes at 4°C (Warraich et al., J Bone Miner Res. 2013 May;28(5):1135-49), obtaining filtered serum samples.

[0336] Afterward, fluorescence was measured at excitation and emission wavelengths of 316 and 456 nm, respectively, using a SpectraMax M5 microplate eader (Molecular Devices, Sunnyvale, CA, USA) with Softmax Pro v5 software. Values were interpolated using linear regression. c. Control and tested food compositions

[0337] Nutrients of maintenance food composition : Moisture 6.5%, Protein 32.5%, Fat 15.3%, Crude fiber 2.0%, Ash 6.6%, Calcium 2.72 g / Mcal, Total Phosphorus 2.44 g / Mcal, Inorganic phosphorus 0.32 g / Mcal, ratio Ca / P 1.11. Calorie content: 3959 kcal ME / kg.

[0338] Ingredients of maintenance food composition: Chicken, Chicken By-Product Meal, Ground Whole Grain Com, Com Grits, Com Gluten Meal, Dried Plain Beet Pulp, Chicken Fat (preserved with Mixed Tocopherols), Natural Flavor, Dried Egg Product, Sodium Bisulfate, Potassium Chloride, Brewers Dried Yeast, Fish Oil (preserved with Mixed Tocopherols), Calcium Carbonate, Choline Chloride, DL-Methionine, Fructooligosaccharides, Vitamins (Vitamin E Supplement, Niacin, Ascorbic Acid, Vitamin A Acetate, Calcium Pantothenate, Biotin, Thiamine Mononitrate (source of Vitamin B1), Pyridoxine Hydrochloride (Source of Vitamin B6), Vitamin B12 Supplement, Riboflavin Supplement (source of Vitamin B2), Inositol, Vitamin D3 Supplement, Folic Acid), Taurine, Minerals (Zinc Oxide, Manganese Sulfate, Copper Sulfate, Potassium Iodide), L-Carnitine, Rosemary Extract.

[0339] The formulas of both tested food compositions (Diet A and B) are identical except for the source of inorganic phosphorus which is either (Diet A) sodium tripolyphosphate or (Diet B) a combination of 50% by weight of inorganic pyrophosphate and 50% by weight of monopotassium phosphate (MKP), based on the total source of inorganic phosphorus. The target inorganic phosphorus level in both food compositions is no more than 1.5 g / Mcal.

[0340] Nutrients of both test food compositions (Diet A and B): Moisture 5.4 %, Protein 34,7%, Fat 14.2%, Crude fiber 3.9%, Ash 11%, Starch 25.6%, NFE 30.8%, Potassium 0.87%, Sodium 0.92%, Magnesium 0.096%, Chlorine 0.91 %, Calcium 5.3 g / Mcal (2.03%), Total Phosphorus 3.8 g / Mcal (1.45%), Inorganic phosphorus 1.5 g / Mcal, ratio Ca / P 1.4. Energy (NRC2006): 3,750 Kcal / kg

[0341] Ingredients of both test food compositions (Diet A and B): Dehydrated poultry protein, maize, rice, animal fats, dehydrated pork protein*LIP, Hydrolyzed poultry protein, yeast, vegetable fibers, beet pulp, fish oil, soy oil, mineral, vitamins.

[0342] Diet A further includes sodium tripolyphosphate (Prayphos™ STPP FG -E451 , Prayon SA), as the source of inorganic phosphorus, in an amount of 2.18% by weight and Diet B further includes a combination of 1.2 % by weight of MKP and 3% by weight of ACPF2 (AFCP2 is an aroma powder purchased from AFB international® which contains inorganic pyrophosphate in an amount to provide 2.5% by weight of inorganic phosphorus, on a dry matter basis).

[0343] B. Results

[0344] It has been shown that cats fed with the food composition containing sodium tripolyphosphate (Diet A) present a significant increase in serum concentration of pyrophosphate 60 minutes after feeding compared to baseline (1.19 ± 0.35 pM vs. 1.03 ± 0.24 pM; p = 0.005; Figure 1), while cats fed with the food compositions containing a combination of monopotassium phosphate (MKP) and inorganic pyrophosphate (Diet B) did not induce a significant alteration in serum concentration of pyrophosphate postfeeding (1.1 ± 0.49 pM vs. 1.07 ± 0.43 pM; p = 0.81 ; Figure 2).

[0345] Therefore, a significant increase in serum pyrophosphate was observed in cats 60 minutes after being fed a food composition containing sodium tripolyphosphate (Diet A) whereas no significant difference is observed in cats fed with the food composition comprising the combination of monopotassium phosphate with inorganic pyrophosphate (MKP + PPi) (Diet B).

[0346] Upon ingestion, tripolyphosphate salts dissociate into ions, including tripolyphosphate and salt ions (potassium or calcium or sodium etc.), within the stomach due to its acidic environment. The released tripolyphosphate ions undergo dephosphorylation by intestinal alkaline phosphatase leading to one pyrophosphate molecule and one monophosphate molecule.

[0347] Consequently, pyrophosphate can result from the metabolism of sodium tripolyphosphate by intestinal alkaline phosphatase, increasing the plasma pyrophosphate level. In contrast, with combining a monophosphate (MKP) with an inorganic pyrophosphate (PPi), the intestinal alkaline phosphatase probably more rapidly metabolizes inorganic pyrophosphate, leading directly to monophosphate.

[0348] Furthermore, it is demonstrated that cats fed with the food composition containing sodium tripolyphosphate (Diet A) present a lower increase in serum concentration of phosphorus 60 minutes after feeding compared to baseline (Figure 3), compared to the food compositions containing a combination of monopotassium phosphate (MKP) and inorganic pyrophosphate (Diet B).

[0349] C. Pyrophosphate from a tripolyphosphate salt can treat and / or protect chronic kidney disease of a cat.

[0350] In cats, an excessive oral consumption of phosphate can disrupt kidney function and potentially lead to chronic kidney disease. In cases of severe kidney dysfunction, the kidney fails to adequately remove phosphate from the organism. Nascent calciprotein monomers and small primary calciprotein from the plasma can be filtered by the kidney into renal tubules. It has been suggested that they act as the nidus for larger more crystalline secondary particles when phosphate concentration exceeds 3 mM in the S3 segment of the proximal tubule. Those crystalline secondary particles are responsible for lysosomal dysfunction, inhibiting autophagy and predisposing to oxidative stress of the renal tubular cells, thus impairing renal function.

[0351] Experimental assays have shown that one way of inhibiting the formation of crystalline secondary nanoparticles could be treating mice with pyrophosphate. Pyrophosphate is a potent endogenous calcification inhibitor that binds to emerging primary crystal nanoparticles and can reduce the tendency for these particles to develop into the crystalline secondary form and the propagation of these crystalline secondary nanoparticles in nephrons, which are harmful for the kidney. Furthermore, inorganic pyrophosphate can inhibit bone mineralisation and soft tissue mineralisation.

[0352] It is surprisingly demonstrated in the present application that the use of a tripolyphosphate salt, as a source of inorganic phosphorus, can allow to provide a significative increase in plasma pyrophosphate level. Hence, the use of a tripolyphosphate salt within food compositions can treat and / or protect and / or delay the progression of the damage of the kidney in cats by exhibiting inhibitory effects on the formation of crystalline secondary nanoparticles and potentially by avoiding excessive inorganic phosphorus intake. Consequently, a rise in plasma pyrophosphate level in cats suffering from chronic kidney disease could treat or delaying the progression of the harmful effects in kidney. In other words, a food composition comprising an effective amount of one or more tripolyphosphate salt can treat a cat suffering of chronic kidney disease, or at least delay the progression of the disease.

[0353] REFERENCES

[0354] Alexander J, Stockman J, Atwal J, Butterwick R, Colyer A, Elliott D, Gilham M, Morris P, Staunton R, Renfrew H, Elliott J, Watson P. Effects of the long-term feeding of diets enriched with inorganic phosphorus on the adult feline kidney and phosphorus metabolism. Br J Nutr. 2019 Feb 14;121 (3):249-269. doi: 10.1017 / S0007114518002751. Epub 2018 Dec 21. PMID: 30572965; PMCID: PMC6390406.

[0355] Coltherd JC, Staunton R, Colyer A, et al. Not all forms of dietary phosphorus are equal: An evaluation of postprandial phosphorus concentrations in the plasma of the cat. British Journal of Nutrition. 2019;121 (3):270-284. doi: 10.1017 / S0007114518003379

[0356] Regulation (EC) No 1333 / 2008 of the European Parliament and of the Council of 16 December 2008 on food additives. OJ L 354, 31.12.2008, p.16

[0357] Kessler, M., & Turner, D. (1997). Stress and Adaptation of Cats (Felis Silvestris Catus) Housed Singly, in Pairs and in Groups in Boarding Catteries. Animal Welfare, 6(3), 243-254. doi: 10.1017 / S0962728600019837

[0358] Warraich S, Bone DB, Quinonez D, li H, Choi DS, Holdsworth DW, Drangova M, Dixon SJ, Seguin CA, Hammond JR. Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans. J Bone Miner Res. 2013 May;28(5):1135- 49.

Claims

CLAIMS1. A food composition including from about 0.1 g / Mcal to about 1.5 g / Mcal of inorganic phosphorus and comprising an effective amount of one or more tripolyphosphate salt, as a source of inorganic phosphorus, for use in a method for treating and / or delaying the progression of chronic kidney disease in a cat in need thereof.

2. The food composition for use according to claim 1 , wherein the one or more tripolyphosphate salt consists of sodium tripolyphosphate (STPP), potassium tripolyphosphate (KTPP) or a mixture thereof, in particular the one or more tripolyphosphate salt consists of sodium tripolyphosphate.

3. The food composition for use according to claim 1 or 2, wherein the food composition includes about 1.0 g / Mcal or less of inorganic phosphorus.

4. The food composition for use according to any one of claims 1 to 3, wherein at least about 0.2 g / Mcal of inorganic phosphorus originates from the one or more tripolyphosphate salt.

5. The food composition for use according to any one of claims 1 to 4, wherein the inorganic phosphorus originates from one or more inorganic pyrophosphate and the one or more tripolyphosphate salt.

6. The food composition for use according to any one of claims 1 to 5, wherein the total amount of inorganic phosphorus originates from the one or more tripolyphosphate salt.

7. The food composition for use according to any one of claims 1 to 6, wherein the food composition further includes calcium and wherein the weight ratio of calcium to phosphorus is characterized by being equal or higher than 1.

8. The food composition for use according to any one of claims 1 to 7, wherein the food composition further includes from about 1 g / Mcal to about 5 g / Mcal of potassium.

9. The food composition for use according to any one of claims 1 to 8, wherein the food composition further includes protein, fat, fibers, and / or vitamins.

10. The food composition for use according to any one of claims 1 to 9, wherein the food composition consists of a nutritionally complete and balanced food composition.

11. The food composition for use according to any one of claims 1 to 10, wherein the food composition consists of a wet, a dry or a semi-moist food composition.

12. The food composition for use according to claim 11 , the food composition being a dry food composition.

13. The food composition for use according to any one of claims 1 to 12, wherein the food composition has a Metabolizable Energy ranging from about 400 kcal / kg to about 5,000 kcal / kg, as measured according to the NRC 2006.

14. The food composition for use according to claim 12 or 13, wherein the food composition has a Metabolizable Energy ranging from about 3,000 kcal / kg to about 5,000 kcal / kg, in particular from about 3,800 kcal / kg to 3,900 kcal / kg, as measured according to the NRC 2006.

15. The food composition for use according to any one of claims 1 to 14, wherein chronic kidney disease affecting the cat involves the deterioration of renal parenchyma; the loss of functional nephrons; and / or the damage and / or the deterioration of the glomerulus.

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