Food composition for treating mineral bone disorder

Abstract

The present disclosure relates to an animal food composition including from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium or a salt thereof, for use in a method for treating and / or preventing a mineral bone disorder, especially mineral bone disorder associated with hypercalcemia, in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction.

Description

FOOD COMPOSITION FOR TREATING MINERAL BONE DISORDERCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to European patent application no. EP 24158831.8, filed on February 21 , 2024, which is incorporated herein by reference in its entirety.FIELD OF THE DISCLOSURE

[0002] The present disclosure relates to the field of food compositions for companion animals. In particular, the present disclosure relates to the field of food compositions for treating and / or preventing mineral bone disorder, especially mineral bone disorder associated with hypercalcemia, in companion animals.BACKGROUND OF THE DISCLOSURE

[0003] Mineral bone disorder, especially mineral bone disorders that are associated with hypercalcemia characterized by elevated levels of calcium in the blood, poses a significant concern in the realm of companion animal healthcare. Among domestic pets, particularly in feline companions, the prevalence of mineral bone disorder, presents a critical challenge in veterinary medicine.

[0004] Mineral bone disorder can manifest due to various underlying factors and is often a result of an imbalance in calcium absorption from the intestines, calcium release from bones, and calcium excretion through the kidneys.

[0005] Symptoms of mineral bone disorder associated with hypercalcemia in cats can vary depending on the underlying cause and the severity of the condition, encompassing increased thirst and urination, vomiting, constipation, weakness, lack of appetite, and in severe instances, potential kidney or heart complications.

[0006] Recent studies have indicated that chronic kidney disease in cats can be a predisposing factor for incident total hypercalcemia, with the majority of cats exhibiting increased total calcium concentration (tCa) concurrently demonstrating ionized hypercalcemia (Van den Broek. J Vet Intern Med. 2017 Mar;31 (2):465-475. doi: 10.1111 / jvim.14643. Epub 2017 Feb 12. PMID: 28190275; PMCID: PMC5354036).

[0007] Some companion animals, in particular felines, are prone to various health issues, including renal dysfunction. Mineral bone disorder in these companionanimals, often associated with renal impairments, imposes a significant burden on both the feline's quality of life and the veterinarian's treatment strategies.

[0008] Current treatment modalities, especially concerning feline patients with renal comorbidities, often lack precision, exhibit limitations in efficacy, or entail potential adverse effects.

[0009] Therefore, there exists a need within the veterinary healthcare landscape for innovative and targeted methods to address mineral bone disorder, especially mineral bone disorder associated with hypercalcemia, in companion animals, specifically custom-made to meet the unique physiological and medical complexities of animals, particularly those facing kidney dysfunction.

[0010] There is a need for novel animal food compositions for treating and / or preventing mineral bone disorder, especially mineral bone disorder associated with hypercalcemia in a companion animal in need thereof.

[0011] There is a need for novel animal food compositions for treating and / or preventing mineral bone disorder, especially mineral bone disorder associated with hypercalcemia in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction, in particular a chronic kidney disease.

[0012] There is a need for novel animal food compositions for treating and / or preventing mineral bone disorder, especially mineral bone disorder associated with hypercalcemia in a companion animal that is affected by a kidney dysfunction and having a dietary phosphate restriction.

[0013] The present disclosure has for purpose to satisfy all or part of the above- mentioned needs.SUMMARY OF THE DISCLOSURE

[0014] An aspect of the present disclosure relates to an animal food composition including from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof, for use in a method for treating and / or preventing a mineral bone disorder in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction.

[0015] Specifically, a kidney dysfunction, in particular chronic kidney dysfunction, in an animal can increase the risk of ionized hypercalcemia due to metabolic acidosis and impaired urinary calcium excretion. Metabolic acidosis, stemming from reduced kidney function, leads to decreased reabsorption of bicarbonate and excretion of hydrogen ions, resulting in reduced HCO3- and elevatedH+ concentrations in the blood. This acidic environment stimulates osteoclastic bone resorption of calcium and reduces the protein-bound calcium fraction. Consequently, concentrations of ionized calcium may rise. A kidney dysfunction can delay the ability to increase calcium excretion, leading to mineral bone disorder associated with ionized hypercalcemia, potentially even with normal total calcium levels in the blood.

[0016] Additionally, animals with kidney dysfunction are generally fed phosphate-restricted food compositions with the goal to control secondary hyperparathyroidism. However, these particular phosphate-restricted food compositions can disrupt calcium homeostasis, sometimes leading to the development of hypercalcemia in certain CKD animals, in particular CKD cats. Specifically, when food compositions are formulated with a very low phosphorus content, calcium content is proportionally higher in these diets (high Ca / P ratio) and can increase concentrations of ionized calcium in the animal blood. Therefore, although some animals can present sign of mineral bone disorder when fed grocery food compositions that are not phosphate restricted, it is believed that dietary phosphate restriction may contribute to the development of mineral bone disorder in animals having kidney disease.

[0017] As illustrated in the example section of the present disclosure, it is surprisingly demonstrated that a food composition supplemented with magnesium can prevent the occurrence of developing mineral bone disorder associated with hypercalcemia in cats having a kidney dysfunction, even if the food composition is restricted in phosphate supplementation. Additionally, it is surprisingly observed that cats fed this phosphate-restricted food composition do not worsen the kidney dysfunction, and may even delay its progression.

[0018] In some embodiments, the animal food composition as disclosed herein can include from about 0.4 g / Mcal to about 0.7 g / Mcal of magnesium or a salt thereof.

[0019] In some embodiments, the animal food composition as disclosed herein can include more than 0.5 g / Mcal to about 0.7 g / Mcal of magnesium or a salt thereof.

[0020] In some embodiments, the animal food composition as disclosed herein is a phosphate-restricted food composition.

[0021] In some embodiments, the mineral bone disorder is a mineral bone disorder associated with hypercalcemia.

[0022] In some embodiments, the companion animal as disclosed herein is affected by, or at risk to be affected by, a kidney dysfunction and can have a magnesium deficiency compared to a predetermined plasma total magnesium concentration,wherein the predetermined plasma total magnesium concentration is based on an average magnesium level in blood in a control population.

[0023] In some embodiments, the kidney dysfunction can be selected from kidney disease involving the deterioration of renal parenchyma, the loss of functional nephrons, or the damage and / or the deterioration of the glomerulus.

[0024] In some embodiments, the kidney dysfunction can be chronic kidney disease (CKD).

[0025] In some embodiments, the companion animal can be affected by, or at risk to be affected by, chronic kidney disease.

[0026] In some embodiments, a magnesium or a salt thereof as used herein can be selected from magnesium oxide, magnesium citrate, magnesium glycinate, magnesium bisglycinate, magnesium aspartate, magnesium chloride, magnesium gluconate, magnesium hydroxide, magnesium carbonate, or a mix thereof.

[0027] In some embodiments, a source of magnesium or a salt thereof is magnesium oxide.

[0028] In some embodiments, the animal food composition as disclosed herein can include from about 0.5 g / Mcal to less than 2 g / Mcal of phosphorus (P).

[0029] In some embodiments, the animal food composition as disclosed herein can include from about 0.7 g / Mcal to about 1 .6 g / Mcal of phosphorus (P).

[0030] In some embodiments, a source of phosphorus can be selected from a phosphate salt, a diphosphate salt and / or a tripolyphosphate salt.

[0031] In some embodiments, the animal food composition as disclosed herein can include from about 1 g / Mcal to about 2 g / Mcal of calcium.

[0032] In some embodiments, the weight ratio of calcium to phosphorus (Ca / P) within the animal food composition as disclosed herein can be characterized by being below or equal to about 2.5.

[0033] In some embodiments, the weight ratio of magnesium to phosphorus (Mg / P) within the animal food composition as disclosed herein can be characterized by being from about 0.1 to about 2.2.

[0034] In some embodiments, the molar ratio of magnesium to phosphorus (Mg / P) within the animal food composition as disclosed herein can be characterized by being from about 0.1 to about 2.8.

[0035] In some embodiments, the animal food composition as disclosed herein can be a nutritionally complete and balanced food composition.

[0036] In some embodiments, the animal food composition can be a wet, a dry or a semi-moist food composition.BRIEF DESCRIPTION OF THE FIGURES

[0037] Figure 1 represents a graph showing the ionized calcium level in control and test cat groups over time. The solid line and dots represent the standard line and cats of test group. The dashed line and crosses represent the standard line and cats of control group. Ordinate: Total ionized calcium level expressed in mmol / L. Abscissa:Duration of the dietary treatment expressed in days.

[0038] Figure 2 represents a graph showing plasma log-transformed fibroblast growth factor 23 (ln[FGF23]) in control and test cat groups over time. The solid line and dots represent the standard line and cats of test group. The dashed line and crosses represent the standard line and cats of control group. Ordinate: Plasma total FGF-23 level expressed in pg / mL. Abscissa: Duration of the dietary treatment expressed in days.

[0039] Figure 3 represents a graph showing the total magnesium plasma level in control and test cat groups over time. The solid line and dots represent the standard line and cats of test group. The dashed line and crosses represent the standard line and cats of control group. Ordinate: Total magnesium level expressed in mmol / L.Duration of the dietary treatment expressed in days.DETAILED DESCRIPTION OF THE DISCLOSURE

[0040] 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.

[0041] 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.

[0042] Numeric ranges are inclusive of the numbers defining the range. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.Definitions

[0043] As used herein, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a salt” can include one salt or a mixture of two salts or more.

[0044] 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 or down (higher or lower).

[0045] 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 products, nutrients or steps which does not include only those products, nutrients or steps but can include other products, nutrients, 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 nutrients 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”.

[0046] 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 a particular nutrients, or steps, but every embodiment might not necessarily include the particular nutrients, or steps. Further, when a particular nutrients, or steps 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 nutrients, or steps in connection with other embodiments whether or notexplicitly 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.

[0047] As used herein, the term “food composition” means a product or composition that is intended for consumption by a companion animal. A food composition contains one or more ingredients in order to incorporate one or more nutrients. Nutrients of a food composition can be typically proteins, fibers, carbohydrates, fats, vitamins and / or minerals, which can be used in combination in the body of an organism to sustain growth, repair and / or 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 further contain a carrier, a diluent, and / or an excipient.

[0048] In the context of the present disclosure, an "ingredient" refers to any individual component or substance that is 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.

[0049] As used herein the term “providing” includes selling, supplying, administering, or feeding an animal, in particular a feline.

[0050] As used herein, the term “weight percent” or “wt%” or “by weight” is meant to refer to the quantity by weight of a nutrient in a food composition as a percentage on a dry matter basis of the food composition, unless otherwise specified. The specified amount of nutrients included in a food composition as described herein represents the amount present in the total quantity of raw materials provided as sources of said nutrients for producing the said food composition.

[0051] The expression “dry matter basis” or “DM” must be interpreted as a method of expressing the concentration of a nutrient 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 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 combinationin 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.

[0052] 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 a disease, the symptoms of a disease, the likelihood of a disease, or to prevent or delay the onset of the symptoms, complications, or otherwise arrest or inhibit further development of a disease in a statistically significant manner. More particularly, “treating” or “treatment” encompasses any approach for obtaining beneficial or desired results in an animal afflicted with a 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 a disease; diminishment or reduction of the severity of a disease or symptoms related to the disease; maintaining the stability (preventing deterioration) of a disease; delaying the progression or slowing down the progression of a disease; minimizing the recurrence of a 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 a disease or related symptom. A “reduction” of a disease, or symptoms of a disease, means decreasing of the severity or frequency of the disease or symptoms of the disease, or elimination of a disease or symptoms of the disease. In the context of the present disclosure, a disease can be mineral bone disorder. In some particular embodiments, a disease can be mineral bone disorder associated with hypercalcemia. In some embodiments, a disease can be a kidney dysfunction, such as chronic kidney disease. In some embodiments, a disease can encompass both mineral bone disorder associated with hypercalcemia and a kidney dysfunction, such as chronic kidney disease-mineral and bone disorder.

[0053] As used herein, the terms “prevent” or “preventing” (and grammatical variants thereof) with respect to a disease relate to prophylactic treatment of a disease, e.g., in a cat suspected to have mineral bone disorder associated with hypercalcemia, or at risk for developing mineral bone disorder associated with hypercalcemia. Prevention may include, but is not limited to, preventing, or delaying onset or progression of a disease and / or maintaining one or more symptoms of a 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 denotesthat 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 mineral bone disorder associated with hypercalcemia or symptoms thereof in an animal. 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.

[0054] As used herein, the term “mineral bone disorder” refers to a condition characterized by abnormalities in mineral metabolism, particularly involving calcium, phosphorus, and vitamin D, which can lead to bone demineralization, weakening, and increased fracture risk in the animal. One of the symptoms of a mineral bone disorder is hypercalcemia in the animal. Mineral bone disorder may be often associated with chronic kidney disease. In the context of the chronic kidney disease, mineral bone disorder associated with hypercalcemia may be linked to nephrocalcinosis and may participate in the progression of CKD.

[0055] As used herein, the term “hypercalcemia” refers to a medical condition characterized by abnormally high levels of calcium in the blood of an animal, typically defined in feline as total blood calcium exceeding 2.9 mmol / L and / or ionized blood calcium (iCa) exceeding 1 .4 mmol / L. Hypercalcemia can have several consequences on an animal, such as the formation of kidney stones, gastrointestinal issues, a mineral bone disorder or cardiac problems.

[0056] As used herein, the term “chronic kidney disease” or “CKD” refers to a progressive condition characterized by a decline in kidney function over an extended period. This disease involves structural and functional abnormalities in the kidneys, leading to a reduced ability to filter waste products from the blood and maintain fluid and electrolyte balance. CKD in animals often manifests as kidney dysfunction accompanied by various clinical signs, such as polyuria, polydipsia, weight loss, and metabolic disturbances including disturbances of phosphate and calcium balance and the hormones that regulate these minerals. This phosphate and calcium balance is often associated with a chronic kidney disease-mineral and bone disorder (CKD-Mineral Bone Disorder).

[0057] As used herein, the term “a chronic kidney disease-mineral and bone disorder (CKD-MBD)” refers to a systemic disorder that encompasses a complex interplay between mineral and hormonal metabolism, bone remodelling and extra-skeletal calcification, that occurs as a result of CKD. CKD-MBD represents a combination of three closely interrelated disease conditions: (1) disturbed mineral and bone metabolism including calcium, phosphorus, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), alkaline phosphatase or vitamin D; (2) abnormalities in bone turnover, mineralization, volume, strength or linear growth, representing the presence of renal osteodystrophy; (3) calcification of the vasculature or other soft tissues (i.e. nephrocalcinosis), and exacerbation of the risk of cardiovascular disease. Techniques of diagnosing CKD-MBD are well known in the art. For instance, CKD-MBD is usually identify first by elevations in FGF23 concentration in the blood as the earliest sign of the disorder.

[0058] As used herein, the terms “animal” or “companion animal” can be used interchangeably to refer to domestic animals. In particular, a companion animal can refer to a canine and / or a feline. In some embodiments, a canine can be a dog and a feline can be a cat.

[0059] 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.

[0060] All lists of items, such as, for example, lists of nutriment or 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.”Units

[0061] As used herein, a concentration of a product as expressed in “mmol / L” refers to millimole per liter.

[0062] As used herein, a concentration of a product as expressed in “pg / mL” refers to picogram per milliliter.

[0063] As used herein, an amount of a nutrient as expressed as weight per megacalories, such as grams per megacalorie (g / Mcal), consists of a weight amount of the said nutrient by unit of Metabolizable Energy (ME) of the food composition.

[0064] 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.

[0065] 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:

[0066] ME (kcal / kg) = [GE - (FE + UE)] I Kg of food consumed.

[0067] 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:

[0068] ME (kcal / kg) = 10 x [(3.5 x CP) + (8.5 x CF) + (3.5 x NFE)].

[0069] In some embodiments, the ME can be determined according to the predictive equation proposed by the National Research Council (NRC) in 2006.

[0070] In a particular embodiment of the disclosure, especially for a cat, the ME, in kcal / 100g, can be calculated as:

[0071] ME = GE x [95.6 - (0.89 x TDF x 100 / DM) ] / 100) - (0.77 x CP)

[0072] or

[0073] ME = GE x [87.9 - (0.88 x CF x 100 / DM) ] / 100) - (0.77 x CP)

[0074] with GE = (5.7 x CP) + (9.4 x CF) + [4.1 x (NFE + CF)]

[0075] In some embodiments, a food composition as disclosed herein can be characterized by its Metabolizable Energy (ME).

[0076] 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.

[0077] In some embodiments, mainly depending on its moisture content, a food composition as disclosed herein can have a Metabolizable Energy (ME) ranging from about 400 kcal / kg to about 1 ,600 kcal / kg, or from about 1 ,600 kcal / kg to about 5,000 kcal / kg, or from about 3,000 kcal / kg to about 5,000 kcal / kg, as measured according to the NRC 2006.

[0078] 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.

[0079] 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 4,500 kcal / kg or from about 3,800 kcal / kg to about 4,300 kcal / kg, as measured according to the NRC 2006.

[0080] In some embodiments, a dry food composition as disclosed herein can have a Metabolizable Energy (ME) of 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, as measured according to the NRC 2006.

[0081] 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.

[0082] 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 ,500 kcal / kg, or from about 800 kcal / kg to about 1 ,400 kcal / kg, or from about 900 kcal / kg to about 1 ,200 kcal / kg as measured according to the NRC 2006.

[0083] In some embodiments, a wet food composition as described herein can have a Metabolizable Energy of about 900 kcal / kg, or about 950 kcal / kg, or about 1 ,000kcal / 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, as measured according to the NRC 2006.

[0084] In some embodiments, a food composition as described herein can be a semi moist food composition, typically having a moisture content ranging from about 12% or more to about 50% or less by weight.

[0085] 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.

[0086] 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.Formulation of the food composition

[0087] The food composition as described herein includes magnesium or a salt thereof, to be used for treating and / or preventing mineral bone disorder, especially mineral bone disorder associated with hypercalcemia, in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction.

[0088] The food composition of the present disclosure is an animal food composition.

[0089] In some embodiments, the food composition can be a phosphate- restricted food composition. Specifically, a phosphate-restricted food compositionincludes less than 2 g / Mcal of phosphorus and wherein said less than 2 g / Mcal of phosphorus encompasses about 1 g / Mcal or less of inorganic phosphorus.

[0090] In the present disclosure, a food composition as described herein can include from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof.

[0091] Without wishing to be bound by any theory, it is believed that a food composition comprising an amount of magnesium higher than 0.8 g / Mcal could potentially lead to the formation of mineral deposits in the urinary tract of animals. These crystal deposits can form stones, which can obstruct the urinary tract, leading to various urinary tract issues such as discomfort, pain, difficulty urinating, and in severe cases, urinary blockage. Additionally, it is believed that an exceeding amount of magnesium can promote gastrointestinal disturbance in the animal being fed such as soft feces and diarrhea.

[0092] In some embodiments, a food composition as described herein can include about 0.3 g / Mcal or more, or about 0.35 g / Mcal or more, or about 0.4 g / Mcal or more, or about 0.45 g / Mcal or more, or about 0.5 g / Mcal or more, or about 0.55 g / Mcal or more, or about 0.6 g / Mcal or more, or about 0.65 g / Mcal or more, or about 0.7 g / Mcal or more, or about 0.75 g / Mcal or more, or about 0.8 g / Mcal of magnesium or a salt thereof.

[0093] In some embodiments, a food composition as described herein can include from about 0.4 g / Mcal to about 0.7 g / Mcal, or from about 0.5 g / Mcal to about 0.7 g / Mcal, or from about 0.5 g / Mcal to about 0.6 g / Mcal of magnesium (Mg) or a salt thereof.

[0094] In some embodiments, a food composition as described herein can include more than 0.5 g / Mcal to about 0.7 g / Mcal, or more than 0.5 g / Mcal to about 0.6 g / Mcal of magnesium (Mg) or a salt thereof.

[0095] In some embodiments, a food composition as described herein can include more than 0.50 g / Mcal, or 0.51 g / Mcal, or 0.52 g / Mcal, or 0.53 g / Mcal, or 0.54 g / Mcal, or 0.55 g / Mcal, or 0.56 g / Mcal, or 0.57 g / Mcal, or 0.58 g / Mcal, or 0.59 g / Mcal, or 0.60 g / Mcal of magnesium (Mg) or a salt thereof.

[0096] Magnesium refers to an essential mineral which is a chemical element with the symbol Mg and atomic number 12.

[0097] In some embodiments, magnesium used in food compositions and methods of the present disclosure can be in a form of a magnesium salt or a magnesium coordination complex.

[0098] In some embodiments, the magnesium is a magnesium salt for example, but not limited to, an acetate salt, a TFA salt, or a formate salt.

[0099] In some embodiments, the magnesium salt comprises an anion (-) (for example, but not limited to, an amino acid anion, acetate, carbonate, chloride, citrate, cyanide, fluoride, nitrate, nitrite, oxide, phosphate or sulfate) bonded via an ionic bond with Mg2+ cation.

[0100] In some embodiments, magnesium is in a form of an inorganic magnesium salt.

[0101] In some embodiments, magnesium can be magnesium oxide, magnesium citrate, magnesium glycinate, magnesium bisglycinate, magnesium aspartate, magnesium chloride, magnesium gluconate, magnesium hydroxide, magnesium carbonate, or a mix thereof.

[0102] In some embodiments, the magnesium is magnesium oxide.

[0103] In some embodiments, the animal food composition as disclosed herein can be a phosphate-restricted food composition.

[0104] In some embodiments, the animal food composition as disclosed herein can include less than about 2 g / Mcal of phosphorus.

[0105] In some embodiments, a food composition as described herein can include from about 0.5 g / Mcal to less than about 2 g / Mcal of phosphorus.

[0106] In some embodiments, a food composition as described herein can include 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 1.1 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 less than about 2 g / Mcal of phosphorus.

[0107] In some embodiments, a food composition as described herein can include from about 0.6 g / Mcal to about 1.9 g / Mcal, or from about 0.7 g / Mcal to about 1.7 g / Mcal, or from about 0.8 g / Mcal to about 1.6 g / Mcal or from about 0.9 g / Mcal to about 1 .5 g / Mcal of phosphorus.

[0108] In some embodiments, a food composition as described herein can include from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof and from about 0.5 g / Mcal to less than about 2 g / Mcal of phosphorus.

[0109] In some embodiments, a source of phosphorus can be a phosphate or a salt thereof.

[0110] In some embodiments, a source of phosphorus is in a form of a phosphate salt. A phosphate salt is in particular a source of inorganic phosphorus in the food composition.

[0111] In some embodiments, a food composition as described herein can include about 1 g / Mcal or less of inorganic phosphorus. In some particular embodiments, a food composition as described herein can include about 0.9 g / Mcal, or about 0.8 g / Mcal, or about 0.7 g / Mcal, or about 0.6 g / Mcal, or about 0.5 g / Mcal, or about 0.6 g / Mcal, or about 0.5 g / Mcal, or about 0.4 g / Mcal, or about 0.3 g / Mcal, or about 0.2 g / Mcal, or about 0.1 g / Mcal of inorganic phosphorus.

[0112] A phosphate salt can include a monophosphate salt, a diphosphate salt and / or a tripolyphosphate salt.

[0113] In some embodiments, a phosphate salt can be, but is not limited to, monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, calcium phosphate, ferric phosphate, magnesium phosphate, ammonium phosphate, sodium diphosphate, potassium diphosphate, calcium diphosphate, disodium dihydrogen diphosphate, trisodium diphosphate, tetrasodium diphosphate, tetrapotassium diphosphate, potassium tripolyphosphate or sodium tripolyphosphate.

[0114] In some embodiments, a food composition as described herein can include from about 1 g / Mcal to about 2 g / Mcal of calcium.

[0115] In some embodiments, a food composition as described can include about 1 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 of calcium.

[0116] Illustratively, a food composition as described herein can include 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.

[0117] In some embodiments, a food composition as described herein can include from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof, from about 0.5 g / Mcal to less than about 2 g / Mcal of phosphorus and from about 1 g / Mcal to about 2 g / Mcal of calcium.

[0118] 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.

[0119] A mineral supplement as a source of calcium can encompass calcium carbonate, calcium citrate, calcium propionate, calcium lactate and / or calcium gluconate.

[0120] 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 below or equal to about 2.5.

[0121] 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 2.5, or from 1 to 2.3, of from 1.2 to 2, or from 1 .3 to 1 .9, or from 1 .3 to 1 .6.

[0122] 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 .3, 1 .4, 1 .5 or 1 .6.

[0123] In some embodiments, a food composition as described herein can include magnesium and phosphorus such that the weight ratio of magnesium to phosphorus (Mg / P) can be characterized by being from about 0.1 to about 2.2.

[0124] In some embodiments, the weight ratio of magnesium to phosphorus (Mg / P) can be characterized by being from about 0.1 to 2.2, or from 0.2 to 2.1 , of from 0.3 to 2, or from 0.3 to 1 .9, or from 0.4 to 1 .6, or from 0.4 to 1 .2.

[0125] In some embodiments, the weight ratio of magnesium to phosphorus (Mg / P) can be characterized by being of about 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 , 1.1 or 1 .2.

[0126] In some embodiments, the molar ratio of magnesium to phosphorus (Mg / P) within the animal food composition as disclosed herein can be characterized by being from about 0.1 to about 2.8.

[0127] In some embodiments, the molar ratio of magnesium to phosphorus (Mg / P) within the animal food composition as disclosed herein can be characterized by being of about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 , 1 .1 , 1 .2, 1 .3, 1 .4, 1 .5, 1 .6, 1 .7, 1.8, 1.9, 2, 2.1 , 2.2, 2.3, 2.3, 2.4, 2.5, 2.6, 2.7, or 2.8.

[0128] In some embodiments, the food composition as described herein can include other nutrients and / or ingredients to provide a food composition suitable for fed an animal, especially a feline.

[0129] In some embodiments, the food composition as described herein can further include, but is not limited to, protein, fat, fibers, carbohydrates and / or vitamins.

[0130] 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.

[0131] 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 animal while not being toxic for the animal.

[0132] A protein source can be selected from, but is not limited to, poultry, poultry meal, poultry by-product, lamb, lamb meals, pork, pork by-product, beef, beef byproducts, white fish, milk proteins, egg, venison, soybean meal, soy protein isolate, rice, soy protein concentrate, maize gluten, wheat gluten, gluten, tofu, green lentils, carrot, potato, beets, corn gluten meal, corn protein concentrate or a combination thereof.

[0133] A fat source can include, without limitation, wheat, soy, sunflower, safflower, rapeseed, olive, borage, flaxseed, peanuts, blackcurrant seed, cottonseed, wheat, germ, corn germ as well as oils derived from these, 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 combinations thereof.

[0134] 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.

[0135] In some embodiments, the food composition as described can also include preservatives, trace elements and / or coloring.

[0136] In some embodiments, a food composition as described herein can further include a diluent and / or an excipient.

[0137] Typically, the total mass weight of all ingredients in a food composition, as described herein, on a dry matter basis, sums up to 100% by weight.

[0138] The food composition as described herein can be a nutritionally complete and balanced food composition or a functional food.

[0139] As used herein, “nutritionally complete and balanced” food composition means that the composition comprises all the essential nutrients in appropriate proportions to meet an animal's dietary requirements for maintaining overall health and well-being. A nutritionally complete and balanced food composition can maintain the body weight of the animal without significant change with the Body Condition Score (BCS). A nutritionally complete and balanced animal food composition ensures that the animal 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 animal can be fed as the sole ration and is capable of sustaining life without additional food (except water).

[0140] 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.

[0141] In some embodiments, a food composition as described herein can consist of a nutritionally complete and balanced food composition.

[0142] 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.

[0143] Illustratively, a nutritionally complete and balanced food composition as described herein can include, but is not limited to, protein, fat, ash, fibers, carbohydrates, calcium, phosphorus, sodium, potassium, magnesium, water, vitamin D and / or vitamin E.

[0144] 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.

[0145] A dry food composition can refer to a food composition having a moisture content of less than about 12% by weight.

[0146] 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.

[0147] In some embodiments, a dry food composition as described herein can have a moisture content ranging from about 5% to about 12% by weight.

[0148] 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.

[0149] Typically, a dry food composition can have a moisture content of about 8% by weight, relative to the total weight of the food composition.

[0150] 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.

[0151] In some embodiments, a dry food composition can be a kibble.

[0152] A semi-moist food composition refers to a food composition having a moisture content ranging from about 12% to about 50 % by weight.

[0153] Typically, 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).

[0154] 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 about28%, or about 29%, or about 30%, or about 31%, or about 32%, or about 33%, or about34%, or about 35%, or about 36%, or about 37%, or about 38%, or about 39%, or about40%, or about 41%, or about 42%, or about 43%, or about 44%, or about 45%, or about46%, or about 47%, or about 48%, or about 49% by weight.

[0155] 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.

[0156] A wet food composition refers to a food composition having a moisture content of more than about 50% by weight.

[0157] 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.

[0158] 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.

[0159] Typically, a wet food composition can have a moisture content of about 80% by weight, relative to the total weight of the food composition.

[0160] In general, a wet food composition is the final product of a process including a final step of sterilization (instead of a drying step).

[0161] In some embodiments, a wet food composition can consist of a chunk form, more particularly of chunks in gravy form.

[0162] In some embodiments, a wet food composition can consist of chunks and gravy, chunks in jelly, loaf, mousse, terrine or bites form.Uses and methods

[0163] The food compositions as described herein are suitable for treating and / or preventing mineral bone disorder, especially mineral bone disorder associated withhypercalcemia, in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction.

[0164] In particular, the food composition contains an amount of magnesium, or a salt thereof, as described in the present disclosure.

[0165] An object of the present disclosure also relates to an animal food composition including from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof, for use in a method for treating and / or preventing a mineral bone disorder, especially mineral bone disorder associated with hypercalcemia, in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction.

[0166] An object of the present disclosure also relates a method for treating and / or preventing mineral bone disorder, especially mineral bone disorder associated with hypercalcemia, in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction, the method comprising at least a step of providing to the companion animal a food composition including from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof.

[0167] An object of the present disclosure also relates to the use of about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof for the manufacture of a medicament for use in a method for treating and / or preventing a mineral bone disorder, especially mineral bone disorder associated with hypercalcemia, in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction.

[0168] In some embodiments, the mineral bone disorder is associated with hypercalcemia.

[0169] In some embodiments, the companion animal is affected by a kidney dysfunction.

[0170] In some embodiments, the companion animal is not known to suffer from a kidney dysfunction.

[0171] In some embodiments, the companion animal can be under a treatment for a kidney dysfunction. In some embodiments, the treatment is a phosphate-restricted food composition. In some embodiments, a phosphate-restricted food composition can be a food composition comprising about 2 g / Mcal or less of phosphorus.

[0172] In some embodiments, a kidney dysfunction can be selected from kidney disease involving the deterioration of renal parenchyma, the loss of functional nephrons, or the damage and / or the deterioration of the glomerulus.

[0173] In some embodiments, the companion animal can be affected by, or at risk to be affected by, a chronic kidney disease (CKD).

[0174] In some embodiments, the companion animal can be affected by, or at risk to be affected by, an azotaemic chronic kidney disease (CKD).

[0175] In some embodiments, the companion animal can be affected by, or at risk to be affected by, a chronic kidney disease-mineral and bone disorder (CKD-MBD).

[0176] In some embodiments, the companion animal can be affected by, or at risk to be affected by, a chronic kidney disease-mineral and bone disorder (CKD-MBD) associated with hypercalcemia.

[0177] In some embodiments, the companion animal can further present a magnesium deficiency compared to a predetermined plasma total magnesium concentration, and wherein the predetermined plasma total magnesium concentration is based on an average magnesium level in blood in a control population.

[0178] Illustratively, a predetermined plasma total magnesium concentration can ranging from about 0.8 mmol / L to about 1.0 mmol / L. In particular, a predetermined plasma total magnesium concentration can be of about 1.0 mmol / L.

[0179] In some embodiments, a food composition as described herein for its use can be formulated to be administered to the animal daily as part of its diet.

[0180] In some embodiments, the food composition as described herein can be fed to an animal thrice every day, twice every day, once every day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, or once every month.

[0181] In some embodiments, the food composition can be fed to an animal one or more times per day. For example, and not by way of limitation, the food composition can be administered once, twice, three, four, five or more times a day.

[0182] In some embodiments, the pet food composition can be fed to an animal in a constant manner, e.g., where the companion animal fed on a constantly available supply of the food composition.

[0183] 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 onlyon specific days of the week, the skilled person can readily modify the food composition accordingly.

[0184] In some embodiments, a food composition as described herein can be provided to the animal 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.

[0185] In some embodiments, a food composition as described herein can be provided to the animal 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 animal exclusively fed the food composition as described herein or (ii) according to a feeding schedule wherein the animal alternating the food composition described herein and another food composition.

[0186] The food compositions and methods as described herein can be useful for a variety of companion animals, including non-human mammals such as canine and feline.

[0187] In some embodiments, the companion animal can be a cat or a dog.

[0188] In some embodiments, the companion animal is a cat.EXAMPLES

[0189] Cats with chronic kidney disease (CKD) can have increased risk of developing mineral bone disorder, especially mineral bone disorder associated with hypercalcemia.

[0190] The present assay evaluate the effect of magnesium-supplemented phosphate-restricted food composition on cats having CKD, as compared with a standard phosphate-restricted food composition, and its impact on ionized calcium, magnesium plasma level and FGF-23 level. FGF-23 being a biomarker of the progression of chronic kidney disease in cats.A. MATERIAL AND METHODSProtocol:

[0191] A test food composition (Mg supplemented phosphate restricted diet, “Mg supplemented PRD”) was compared to a control food composition (Control phosphate restricted diet, “Control PRD”).

[0192] Test group included 21 cats and control group included 23 adult cats. All cats being diagnosed with a chronic kidney disease (CKD).

[0193] Cats have been randomly allocated to one of two treatment groups during 16 weeks :

[0194] - Control food composition: Royal Canin Renal feline diet, containing 0.15 g / Mcal of magnesium (Table 1).

[0195] - Test food composition: similar to Control food composition except on magnesium inclusion rate: 0.6 g / Mcal of magnesium (through magnesium oxide supplementation).

[0196] Both diets were available in dry and wet version. Cats were either be dry feeders, wet feeders or mix-feeders, as formulation logics for dry and wet versions are very close and the nutritional parameter assessed (magnesium level) is similar between dry and wet version. The cats consumed more than 50% of their allocated food, and well tolerated the diets.

[0197] Inclusion criteria of the cats:

[0198] - Diagnosis of stable azotaemic CKD IRIS (International Renal Interest Society) stage 2 or 3

[0199] - Stabilised on Royal Canin Renal feline diet for a minimum of 4 weeks

[0200] - Plasma total magnesium concentration tMg <1 .0 mmol / L

[0201] - Euthyroid (total thyroxine concentration <40 nmol / L)Table 1 : Control food compositionOther key nutrients: Protein, fat, fibre, ash, carbohydrate, sodium, potassium, vitamin D, vitamin EVariable and parameters:

[0202] The effect of dietary magnesium supplementation on magnesium and FGF-23 (fibroblast growth factor 23) plasma status were determined by:

[0203] - Change in plasma total magnesium concentration between baseline, 4- 8 and 12-16 weeks visits for both treatment groups,

[0204] - Comparison of the average slope of the plot of plasma total magnesium concentration versus time for each treatment group.

[0205] - Comparison of the proportion of each treatment group with plasma total magnesium concentration <1 .0 mmol / L at the 4-8 and 12-16 weeks visits compared to baseline.

[0206] - Change in fractional excretion of magnesium in urine (used as a marker of body magnesium status) between baseline, 4-8 and 12-16 weeks visits for both treatment groups

[0207] - Change in plasma FGF-23 concentration between baseline, 4-8 and 12- 16 weeks visits for both treatment groups

[0208] - Comparison of the average slope of the plot of plasma FGF-23 concentration versus time for each treatment group

[0209] - Comparison of the proportion of each group with plasma FGF-23 concentration >700 pg / mL at the 4-8 and 12-16 weeks visits compared to baseline.

[0210] The effects of oral magnesium supplementation on ionized calcium level involved in feline CKD-MBD were determined by:

[0211] Change in ionised and total calcium concentrations between baseline, 4- 8 and 12-16 weeks visits for both treatment groups; comparison of the average slope of the plot of plasma ionised and total calcium concentration versus time for each treatment group.Methods

[0212] Plasma total magnesium, and total calcium concentrations were analysed on heparinized plasma samples.

[0213] Ionized calcium and venous blood gasses were measured using a point- of-care analyser.

[0214] Plasma FGF-23 concentrations were measured using validated ELISA and IRMA assays.

[0215] Baseline data of the two groups of cats were be compared by independent two-sample t-tests or Mann Whitney U test, and proportions by chi-square test.

[0216] Changes in variables across all visits were compared and the effect of diet, time, and the interaction of diet and time on these changes was assessed using linear mixed measure models for continuous variables and a generalised linear mixed model based on a binomial distribution for categorical variables.B. RESULTS

[0217] The rate of change for ionized blood calcium (iCa) concentration was significantly different (P = 0.012) between the two groups. Blood iCa concentration trended downwards in cats fed the test food composition (Mg supplemented PRD) (p, - 0.023 ± 0.012 mmol / L per month; P = 0.061 ), whereas blood iCa concentration trended upwards in cats fed the control food composition (PRD) (p, 0.021 ± 0.011 mmol / L per month; P = 0.078) (see Fig 1 ).

[0218] Although the rate of change of LnFGF23 plasma level was not significantly different between cats fed the control food composition (Control PRD) and cats fed the test food composition (Mg supplemented PRD) (p=0.251 ), plasma ln[FGF23] concentrations increased significantly over time in cats fed the control food composition (p, 0.138 ± 0.049 pg / mL per month; P = 0.009) while the rate of changewas not significantly different from 0 in cats fed the test food composition (p, 0.051 ± 0.056 pg / mL per month; P = 0.368) (see Fig 2).

[0219] The rate of change was significantly different between groups for total magnesium (P = 0.02). Plasma total magnesium concentration increased significantly over time in cats fed the test food composition (Mg supplemented PRD) (p, 0.101 ± 0.027 mmol / L per month; P < 0.001) but not in cats fed the control food composition (PRD) (P, 0.010 ± 0.025 mmol / L per month; P = 0.691) (Fig 3).

[0220] Results from this study demonstrated that plasma total magnesium concentration was substantially increased in CKD cats fed a magnesium-enriched phosphate-restricted food composition for 4 months; these cats also exhibited greater stability in their plasma FGF-23 and ionized (iCa) concentrations over time compared to the CKD cats fed a control food composition.

[0221] CKD cats fed a magnesium-enriched phosphate-restricted food composition were less likely to develop an increase in iCa over the study period (11 .8% vs. 52.9%; P = 0.026); 4 cats from the control group developed overt ionized hypercalcemia (blood [iCa] >1.5 mmol / L), whereas no cats developed ionized hypercalcemia in the test group.

[0222] The results from this assay demonstrated a benefit of dietary magnesium supplementation on the control of hypercalcemia in cats having CKD with low or normal plasma concentration of total magnesium.

[0223] Additionally, these results indicate that a food composition supplemented with magnesium, while restricted in phosphate supplementation, can delay the progression of chronic kidney disease and prevent mineral bone disorder associated with hypercalcemia.

Claims

CLAIMS1 . An animal food composition including from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium or a salt thereof, for use in a method for treating and / or preventing a mineral bone disorder in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction.

2. The animal food composition for use according to claim 1 , wherein the food composition includes from about 0.4 g / Mcal to about 0.7 g / Mcal of magnesium or a salt thereof.

3. The animal food composition for use according to claim 1 or 2, wherein the food composition includes more than 0.5 g / Mcal to about 0.7 g / Mcal of magnesium or a salt thereof.

4. The animal food composition for use according to any one of claims 1 to 3, wherein the mineral bone disorder is a mineral bone disorder associated with hypercalcemia.

5. The animal food composition for use according to any one of claims 1 to 4, wherein the companion animal is affected by, or at risk to be affected by, a kidney dysfunction and has a magnesium deficiency compared to a predetermined plasma total magnesium concentration, wherein the predetermined plasma total magnesium concentration is based on an average magnesium level in blood in a control population.

6. The animal food composition for use according to any one of claims 1 to 5, wherein the kidney dysfunction is selected from kidney disease involving the deterioration of renal parenchyma, the loss of functional nephrons, or the damage and / or the deterioration of the glomerulus.

7. The animal food composition for use according to any one of claims 1 to 6, wherein the kidney dysfunction is chronic kidney disease (CKD).

8. The animal food composition for use according to any one of claims 1 to 7, wherein the magnesium or a salt thereof is selected from magnesium oxide, magnesiumcitrate, magnesium glycinate, magnesium bisglycinate, magnesium aspartate, magnesium chloride, magnesium gluconate, magnesium hydroxide, magnesium carbonate, or a mix thereof.

9. The animal food composition for use according to any one of claims 1 to 8, wherein the food composition includes from about 0.5 g / Mcal to less than 2 g / Mcal of phosphorus.

10. The animal food composition for use according to claim 9, wherein the source of phosphorus is selected from a phosphate salt, a diphosphate salt and / or a tripolyphosphate salt.

11. The animal food composition for use according to any one of the preceding claims, wherein the food composition includes from about 1 g / Mcal to about 2 g / Mcal of calcium .

12. The animal food composition for use according to any of the preceding claims, wherein the weight ratio of calcium to phosphorus (Ca / P) can be characterized by being below or equal to about 2.5.

13. The animal food composition for use according to any of the preceding claims, wherein the weight ratio of magnesium to phosphorus (Mg / P) can be characterized by being from about 0.1 to about 2.2.

14. The animal food composition for use according to any one of the preceding claims, wherein the food composition is a nutritionally complete and balanced food composition.

15. The animal food composition for use according to any one of the preceding claims, wherein the food composition is a wet, a dry or a semi-moist food composition.

16. A method for treating and / or preventing a mineral bone disorder in a companion animal that is affected by, or at risk to be affected by, a kidney dysfunction, the methodcomprising at least a step of providing to the companion animal a food composition including from about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof.

17. The method of claim 16, wherein the mineral bone disorder is associated with hypercalcemia.

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