Food composition for treating mineral bone disorders

Abstract

This disclosure relates to an animal food composition comprising about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium or a salt thereof, said animal food composition being used in methods for treating and / or preventing mineral skeletal disorders in companion animals affected by or at risk of being affected by renal dysfunction, particularly mineral skeletal disorders associated with hypercalcemia.

Description

[0001] Cross-references to related applications This application claims priority to European Patent Application No. EP 24158831.8, filed on 21 February 2024, which is incorporated herein by reference in its entirety. Technical Field

[0002] This disclosure relates to the field of food compositions for companion animals. Specifically, this disclosure relates to the field of food compositions for treating and / or preventing mineralogy disorders in companion animals, particularly mineralogy disorders associated with hypercalcemia. Background Technology

[0003] Mineral bone disorders, particularly those associated with hypercalcemia characterized by elevated blood calcium levels, have garnered significant attention in companion animal health. The prevalence of mineral bone disorders among domestic pets, especially feline companion animals, presents a serious challenge for veterinarians.

[0004] Mineral bone disorders can be caused by a variety of underlying factors and are usually the result of an imbalance between calcium absorption in the intestines, calcium release from bones, and calcium excretion through the kidneys.

[0005] Symptoms of feline hypercalcemia-associated mineral skeletal disease can vary depending on the underlying cause and the severity of the condition, and may include increased thirst and urination, vomiting, constipation, weakness, loss of appetite, and, in severe cases, kidney or heart complications.

[0006] Recent studies have shown that chronic kidney disease in cats may be a predisposing factor for total hypercalcemia, in which most cats exhibit increased total calcium concentration (tCa) along with ionized hypercalcemia (Van den Broek. Journal of Veterinary Internal Medicine). J Vet Intern Med ) . March 2017; 31(2):465-475. doi: 10.1111 / jvim.14643. Electronic version February 12, 2017. PMID: 28190275; PMCID: PMC5354036).

[0007] Some companion animals, particularly felines, are prone to a variety of health problems, including kidney dysfunction. Mineral skeletal disorders in these companion animals are often associated with kidney damage, placing a significant burden on both the feline's quality of life and veterinary treatment strategies.

[0008] Current treatments, especially for feline patients with kidney complications, often lack precision, exhibit limited efficacy, or carry the risk of adverse reactions.

[0009] Therefore, there is a need in the field of veterinary healthcare for innovative and targeted approaches to address mineraloskeletal disorders in companion animals, particularly those associated with hypercalcemia, tailored to meet the unique physiological and medical complexities of animals, especially those facing renal dysfunction.

[0010] There is a need for novel animal food compositions for the treatment and / or prevention of mineral skeletal disorders in companion animals, particularly those associated with hypercalcemia.

[0011] There is a need for novel animal food compositions for the treatment and / or prevention of mineral skeletal disorders, particularly those associated with hypercalcemia, in companion animals affected by or at risk of renal dysfunction (especially chronic kidney disease).

[0012] There is a need for novel animal food compositions for the treatment and / or prevention of mineral bone disorders, particularly those associated with hypercalcemia, in companion animals affected by renal dysfunction and with dietary phosphate restriction.

[0013] The purpose of this disclosure is to satisfy all or some of the needs mentioned above. Summary of the Invention

[0014] One aspect of this disclosure relates to an animal food composition comprising about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof, said animal food composition being used in a method for treating and / or preventing mineral bone disorders in companion animals affected by or at risk of being affected by kidney dysfunction.

[0015] Specifically, renal dysfunction in animals, particularly chronic renal dysfunction, can increase the risk of ionized hypercalcemia due to metabolic acidosis and impaired urinary calcium excretion. Metabolic acidosis caused by decreased renal function leads to reduced bicarbonate reabsorption and hydrogen ion excretion, resulting in decreased HCO3- concentration and increased H+ concentration in the blood. This acidic environment inhibits osteoclast-mediated bone resorption and reduces protein-bound calcium fractions. Consequently, ionized calcium concentrations may rise. Renal dysfunction can delay the ability to increase calcium excretion, leading to mineralosclerosis associated with ionized hypercalcemia, even when total blood calcium levels are normal.

[0016] In addition, animals with renal dysfunction are often fed phosphate-restricted food compositions to control secondary hyperparathyroidism. However, these specific phosphate-restricted food compositions can disrupt calcium homeostasis and sometimes lead to hypercalcemia in some CKD animals, particularly CKD cats. Specifically, when the food composition is formulated with very low phosphorus content, the calcium content in these diets is proportionally higher (high Ca / P ratio), which can increase the concentration of ionized calcium in the animal's blood. Therefore, although some animals may show signs of mineralosolidosis when fed unrestricted phosphate-containing grocery compositions, it is believed that dietary phosphate restriction may lead to mineralosolidosis in animals with renal disease.

[0017] As demonstrated in the Examples section of this disclosure, it has been surprisingly demonstrated that even when the food composition is restricted in terms of phosphate supplementation, magnesium-supplemented food compositions can prevent cats with renal dysfunction from developing mineral skeletal disorders associated with hypercalcemia. Furthermore, it has been surprisingly observed that feeding cats with this phosphate-restricted food composition does not worsen their renal dysfunction and may even delay its progression.

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

[0019] In some embodiments, the animal food composition disclosed herein may include magnesium or a salt thereof in amounts ranging from more than 0.5 g / Mcal to about 0.7 g / Mcal.

[0020] In some embodiments, the animal food compositions disclosed herein are phosphate-restricted food compositions.

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

[0022] In some embodiments, the companion animals disclosed herein are affected by or at risk of being affected by renal dysfunction and may suffer from magnesium deficiency compared to a predetermined total plasma magnesium concentration, wherein the predetermined total plasma magnesium concentration is based on the mean magnesium level in the blood of a control group.

[0023] In some embodiments, renal dysfunction may be selected from kidney diseases involving the following: deterioration of renal parenchyma, loss of functional nephrons, or glomerular damage and / or deterioration.

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

[0025] In some embodiments, companion animals may be affected by or at risk of being affected by chronic kidney disease.

[0026] In some embodiments, magnesium or its salts, as used herein, may be selected from magnesium oxide, magnesium citrate, magnesium glycine, magnesium diglycine, magnesium aspartate, magnesium chloride, magnesium gluconate, magnesium hydroxide, magnesium carbonate, or mixtures thereof.

[0027] In some embodiments, the source of magnesium or its salt is magnesium oxide.

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

[0029] In some embodiments, the animal food composition disclosed herein may include phosphorus (P) of about 0.7 g / Mcal to about 1.6 g / Mcal.

[0030] In some embodiments, the source of phosphorus may be selected from phosphates, diphosphates, and / or tripolyphosphates.

[0031] In some embodiments, the animal food composition disclosed herein may include calcium at a concentration of about 1 g / Mcal to about 2 g / Mcal.

[0032] In some embodiments, the weight ratio of calcium to phosphorus (Ca / P) in the animal food composition disclosed herein may be less than or equal to about 2.5.

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

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

[0035] In some embodiments, the animal food compositions disclosed herein may be nutritionally complete and balanced food compositions.

[0036] In some embodiments, the animal food composition may be a wet food composition, a dry food composition, or a semi-wet food composition. Attached Figure Description

[0037] Figure 1 This graph shows the ionic calcium levels of the control and test cat groups over time. Solid lines and dots represent the standard line and cats in the test group. Dashed lines and crosses represent the standard line and cats in the control group. ordinate Total ionized calcium level, expressed in mmol / L. x-axis : Duration of dietary therapy, expressed in days.

[0038] Figure 2 The graph shows the plasma log-converted fibroblast growth factor 23 (ln[FGF23]) levels over time in the control and test cat groups. Solid lines and dots represent the standard line for the test group and cats. Dashed lines and crosses represent the standard line for the control group and cats. ordinate Total plasma FGF-23 level, expressed in pg / mL. x-axis : Duration of dietary therapy, expressed in days.

[0039] Figure 3 This graph shows the total plasma magnesium levels over time in the control and test cat groups. Solid lines and dots represent the standard line and cats in the test group. Dashed lines and crosses represent the standard line and cats in the control group. ordinate Total magnesium level, expressed in mmol / L. x-axis : Duration of dietary therapy, expressed in days. Detailed Implementation

[0040] Within the context of this disclosure and in the specific context in which each term is used, the terms used herein generally have their common meaning in the art. Certain terms are discussed below or elsewhere in this specification to provide additional guidance in describing the compositions and methods of this disclosure and how they are prepared and used.

[0041] Exemplary methods and food compositions are described below, but methods and food compositions similar to or equivalent to those described herein may also be used in the practice or testing of this disclosure. Furthermore, unless the context otherwise requires, singular terms shall include plural terms, and plural terms shall include singular terms.

[0042] Numerical ranges include the numerical endpoints of the defined range. Therefore, the terms defined below are further defined in more detail by referring to the entire contents of this specification.

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

[0044] As used herein, the term “about” means within an acceptable margin of error for a 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. Generally, the term “about” can modify values ​​above and below the specified value by, for example, a variance of more than or less than 10% (higher or lower).

[0045] As used herein, the terms “comprise,” “comprising,” “include,” “including,” or any other variations thereof are intended to cover a non-exclusive inclusion, such that a food composition, process, or method that includes or comprises a list of products, nutrients, or steps may include not only those products, nutrients, or steps but also other products, nutrients, or steps not expressly listed or inherent to such food compositions, processes, or methods. The term “composes of” means to include the specified elements, excluding any additional nutrients or steps. The term “substantially constitutes” means to include the specified elements as well as possible other elements, wherein the other elements do not materially affect the basic and novel characteristics of this disclosure. It should be understood that different embodiments of this disclosure using the term “comprising” or its equivalents cover embodiments in which the term is replaced by “composes of” or “substantially constitutes”.

[0046] In the detailed description herein, references to "embodiment," "an embodiment," "one embodiment," "in some embodiments," or any other variations thereof indicate that the described embodiment may include a specific nutrient or step, but not every embodiment necessarily includes that specific nutrient or step. Furthermore, when a specific nutrient or step is described in connection with an embodiment, it is believed that steps affecting such nutrients or related to other embodiments are within the knowledge of those skilled in the art, whether explicitly described or not. After reading this specification, those skilled in the art will understand how to implement this disclosure in alternative embodiments.

[0047] As used herein, the term "food composition" means a product or composition intended for consumption by companion animals. A food composition contains one or more ingredients to incorporate one or more nutrients. The nutrients in a food composition can typically be proteins, fiber, carbohydrates, fats, vitamins, and / or minerals, which can be used in combination within an organism to maintain growth, repair, and / or life processes, and to provide energy (defined in metabolizable energy (ME)). Carbohydrates include NFE (nitrogen-free extract). Food compositions disclosed herein may further contain carriers, diluents, and / or excipients.

[0048] In the context of this disclosure, "ingredient" means any individual component or substance included in a formulation of a food composition. Ingredients can be of various types, such as sources of proteins, carbohydrates, fats, vitamins, minerals, flavorings, preservatives, and / or other additives. Ingredients can be raw materials, raw material byproducts, additives, and / or nutritional supplements. The selection and combination of ingredients are essential for producing a comprehensive and balanced food composition.

[0049] As used herein, the term “provide” includes the sale, supply, management, or feeding of animals, particularly felines.

[0050] As used herein, unless otherwise stated, the terms "percentage by weight" or "wt%" or "by weight" mean the amount of a nutrient in a food composition by weight, expressed as a percentage of the dry matter basis of the food composition. As described herein, a specified amount of a nutrient included in a food composition means the amount present in the total amount of raw materials provided as a source of said nutrient for producing 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 indicating its concentration relative to its dry matter content (the concentration remaining after water has been removed). Conversely, the expression "as fed" must be interpreted as a method of expressing the concentration of a nutrient in a food composition by indicating its concentration in a feeding state, which includes water. It should be understood that certain features of this disclosure described in the context of individual embodiments for clarity may also be provided in combination in individual embodiments. Conversely, for simplicity, various features of this disclosure described in the context of individual embodiments may also be provided individually or in any suitable sub-combination.

[0052] As used herein, the term "treating" or "treatment" means the application of a food composition according to the present disclosure for the purpose of treating, alleviating, relieving, altering, remedying, reducing, improving, or influencing a disease, its symptoms, its likelihood, or preventing or delaying the onset of symptoms or complications, or stopping or inhibiting the further development of a disease in a statistically significant manner. More specifically, "treating" or "treatment" encompasses any method used to obtain a beneficial or desired outcome in an animal suffering from a disease. Beneficial or desired clinical outcomes may include, but are not limited to, alleviating or reducing one or more symptoms or symptom associated with the disease; reducing or lessening the severity of the disease or symptoms associated with the disease; maintaining the stability of the disease (preventing deterioration); delaying or slowing the progression of the disease; minimizing the recurrence of the disease; and relief, whether partial or overall, whether detectable or undetectable. In other words, "treatment" as used herein includes any cure, relief, or reduction of a disease or related symptoms. "Reduction" of a disease or its symptoms means a reduction in the severity or frequency of the disease or symptoms, or the elimination of the disease or symptoms. In the context of this disclosure, a disease may be a mineral skeletal disorder. In some specific embodiments, the disease may be a mineralogy disorder associated with hypercalcemia. In some embodiments, the disease may be a renal impairment, such as chronic kidney disease. In some embodiments, the disease may encompass both a mineralogy disorder associated with hypercalcemia and a renal impairment, such as chronic kidney disease-mineral and bone disorders.

[0053] As used herein, the term “prevent” or “preventing” (and its grammatical variations) refers to preventive treatment of a disease, such as in cats suspected of having or at risk of developing a mineraloskeletal disorder associated with hypercalcemia. Prevention may include, but is not limited to, preventing or delaying the onset or progression of a disease, and / or maintaining one or more symptoms of the disease at a desired or subpathological level. The term “prevent” does not require the complete elimination of the likelihood or probability of an event occurring. Rather, it indicates that the likelihood of an event occurring has been reduced in the presence of the composition or method described herein. More specifically, “prevent” or “preventing” refers to reducing the risk of an animal developing a mineraloskeletal disorder associated with hypercalcemia or its symptoms. As indicated above, prevention can be complete, i.e., no detectable symptoms or disease; or partial, resulting in fewer or less severe observed symptoms of chronic kidney disease compared to what might have occurred without treatment.

[0054] As used herein, the term "mineral bone disorder" refers to a condition characterized by abnormal mineral metabolism, particularly involving calcium, phosphorus, and vitamin D, which can lead to bone demineralization, weakening, and an increased risk of fractures in animals. One symptom of mineral bone disorder is hypercalcemia in animals. Mineral bone disorder is often associated with chronic kidney disease (CKD). In the context of CKD, mineral bone disorder associated with hypercalcemia may be related to nephrocalcinosis and may be involved 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 felines as total blood calcium exceeding 2.9 mmol / L and / or ionized calcium (iCa) exceeding 1.4 mmol / L. Hypercalcemia can have several consequences for animals, such as kidney stone formation, gastrointestinal problems, mineral bone disorders, or heart 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 of the kidneys, leading to a reduced ability to filter waste from the blood and maintain fluid and electrolyte balance. In animals, CKD typically presents as kidney dysfunction accompanied by a variety of clinical signs, such as polyuria, polydipsia, weight loss, and metabolic disturbances, including phosphate and calcium imbalances and hormonal disturbances that regulate these minerals. This phosphate and calcium imbalance is often associated with chronic kidney disease-mineral and bone disease (CKD mineral and bone disease).

[0057] As used herein, the term “chronic kidney disease-mineral and bone disorder (CKD-MBD)” refers to a systemic condition encompassing the complex interactions between mineral and hormone metabolism, bone remodeling, and extraosseous calcification, which are consequences of CKD. CKD-MBD represents a combination of three closely related disease symptoms: (1) disturbances in 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, indicating the presence of renal osteodystrophy; and (3) calcification of the vascular system or other soft tissues (i.e., nephrocalcinosis) and increased risk of cardiovascular disease. Techniques for diagnosing CKD-MBD are well known in the art. For example, CKD-MBD is often first identified by elevated levels of FGF23 in the blood (as the earliest sign of the condition).

[0058] As used herein, the terms "animal" or "companion animal" are used interchangeably to refer to domestic animals. Specifically, companion animals can refer to canines and / or felines. In some embodiments, canines can be dogs, and felines can be cats.

[0059] It should be understood that each maximum numerical limit given in this specification includes each lower numerical limit, as such lower numerical limit is explicitly stated herein. Each minimum numerical limit given throughout this specification includes each higher numerical limit, as such higher numerical limit is explicitly stated herein. Each numerical range given throughout this specification includes each narrower numerical range falling within such a wider numerical range, as such narrower numerical range is explicitly stated herein.

[0060] All lists of items, such as lists of nutrients or ingredients, are intended and should be interpreted as Markush groups. Therefore, all lists can be read and interpreted as “groups selected from the list of items” and “combinations and mixtures thereof.”

[0061] unit As used in this article, the concentration of a product expressed in "mmol / L" refers to millimoles per liter.

[0062] As used in this article, the concentration of a product expressed in "pg / mL" refers to picograms per milliliter.

[0063] As used herein, the amount of a nutrient expressed in weight per megacalorie, such as grams per megacalorie (g / Mcal), consists of the weight of the nutrient and is expressed in units 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 this disclosure, the ME value can be measured by any suitable method known in the art.

[0065] Examplely, a feeding trial can be used to measure the ME value. In practice, the total energy (GE) of the food composition is determined in a laboratory, and the amount of food consumed by the animals is recorded. Feces and urine are collected from the animals, and the energy of each is determined, referred to as fecal energy (FE) and urinary energy (UE), respectively. The ME can then be calculated as: ME (kcal / kg) = [GE - (FE + UE)] / Kg of food consumed.

[0066] Alternatively, the ME value can be measured using standard mathematical methods, taking into account the percentages of crude fat (CF), crude protein (CP), non-fat protein (NFE), and / or total dietary fiber (TDF) in the food composition according to the method. In practice, each percentage is multiplied by its respective Atwater Factor. The sum of the results is then multiplied by 10. The mathematical method can be expressed as follows: ME (kcal / kg) = 10 × [(3.5 × CP) + (8.5 × CF) + (3.5 × NFE)].

[0067] In some embodiments, ME can be determined based on the prediction equation proposed by the National Research Council (NRC) in 2006.

[0068] In specific embodiments of this disclosure, particularly for cats, ME in kcal / 100 g can be calculated as: ME = GE × [95.6 - (0.89 × TDF × 100 / DM)] / 100) - (0.77 × CP) or ME = GE × [87.9 - (0.88 × CF × 100 / DM) ] / 100) - (0.77 × CP) Where GE = (5.7 × CP) + (9.4 × CF) + [4.1 × (NFE + CF)] In some embodiments, the food composition disclosed herein may be characterized by its metabolizable energy (ME).

[0069] In some embodiments, the food composition, as disclosed herein and measured according to NRC 2006, may have a metabolizable energy (ME) ranging from about 400 kcal / kg to about 5,000 kcal / kg.

[0070] In some embodiments, depending primarily on their moisture content, food compositions disclosed herein may have 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 NRC 2006.

[0071] In some embodiments, the food composition described herein may be a dry food composition having a moisture content typically ranging from about 5% by weight to about 12% by weight.

[0072] In some embodiments, the dry food composition as described herein may have 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 NRC 2006.

[0073] In some embodiments, the dry food compositions disclosed herein may have metabolizable energy (ME) in the range 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 NRC 2006.

[0074] In some embodiments, the food composition as described herein may be a wet food composition having a moisture content typically ranging from about 50% by weight to about 90% by weight.

[0075] In some embodiments, the wet food composition as described herein may have metabolizable energy ranging from about 400 kcal / kg to about 1,600 kcal / kg, or about 600 kcal / kg to about 1,500 kcal / kg, or about 800 kcal / kg to about 1,400 kcal / kg, or about 900 kcal / kg to about 1,200 kcal / kg as measured according to NRC 2006.

[0076] In some embodiments, the wet food composition as described herein may have a metabolizable energy of 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 as measured according to NRC 2006.

[0077] In some embodiments, the food composition described herein may be a semi-wet food composition having a moisture content typically ranging from about 12% by weight or higher to about 50% by weight or lower.

[0078] In some embodiments, the semi-wet food composition as described herein may have a metabolizable energy ranging from about 1,600 kcal / kg to about 5,000 kcal / kg as measured according to NRC 2006.

[0079] In some embodiments, the semi-wet food composition as described herein may have a content 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, as measured according to NRC 2006. kcal / kg, or approximately 2,550 kcal / kg, or approximately 2,600 kcal / kg, or approximately 2,650 kcal / kg, or approximately 2,700 kcal / kg, or approximately 2,750 kcal / kg, or approximately 2,800 kcal / kg, or approximately 2,850 kcal / kg, or approximately 2,900 kcal / kg, 3,000 kcal / kg, or approximately 3,100 kcal / kg, or approximately 3,200 kcal / kg, or approximately 3,300 kcal / kg, or approximately 3,400 kcal / kg, or approximately 3,500 kcal / kg, or approximately 3,600 kcal / kg, or approximately 3,700 kcal / kg, or approximately 3,800 kcal / kg, or approximately 3,900 kcal / kg, or approximately 4,000 kcal / kg. Metabolizable energy of approximately 4,100 kcal / kg, or approximately 4,200 kcal / kg, or approximately 4,300 kcal / kg, or approximately 4,400 kcal / kg, or approximately 4,500 kcal / kg, or approximately 4,600 kcal / kg, or approximately 4,700 kcal / kg, or approximately 4,800 kcal / kg, or approximately 4,900 kcal / kg, or approximately 5,000 kcal / kg.

[0080] Formulation of food compositions Food compositions as described herein include magnesium or its salts for the treatment and / or prevention of mineral skeletal disorders in companion animals affected by or at risk of renal dysfunction, particularly mineral skeletal disorders associated with hypercalcemia.

[0081] The food composition disclosed herein is an animal food composition.

[0082] In some embodiments, the food composition may be a phosphate-restricted food composition. Specifically, the phosphate-restricted food composition comprises less than 2 g / Mcal of phosphorus, and said less than 2 g / Mcal of phosphorus includes about 1 g / Mcal or less of inorganic phosphorus.

[0083] In this disclosure, food compositions as described herein may include magnesium (Mg) or a salt thereof at about 0.3 g / Mcal to about 0.8 g / Mcal.

[0084] Without being bound by any theory, it is believed that food compositions containing magnesium levels above 0.8 g / Mcal may lead to the formation of mineral deposits in the urinary tract of animals. These crystalline deposits can form stones, which can block the urinary tract, causing various urinary problems such as discomfort, pain, difficulty urinating, and in severe cases, urinary tract obstruction. Additionally, excessive magnesium is believed to promote gastrointestinal disorders in fed animals, such as soft stools and diarrhea.

[0085] In some embodiments, the food composition as described herein may 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.

[0086] In some embodiments, the food composition as described herein may include magnesium (Mg) or a salt thereof in amounts of about 0.4 g / Mcal to about 0.7 g / Mcal, or about 0.5 g / Mcal to about 0.7 g / Mcal, or about 0.5 g / Mcal to about 0.6 g / Mcal.

[0087] In some embodiments, the food composition as described herein may include magnesium (Mg) or a salt thereof in amounts of 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.

[0088] In some embodiments, the food composition as described herein may include magnesium (Mg) or a salt thereof in amounts exceeding 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.

[0089] Magnesium is an essential mineral, a chemical element with the symbol Mg and atomic number 12.

[0090] In some embodiments, magnesium used in the food compositions and methods of this disclosure may be in the form of magnesium salts or magnesium coordination complexes.

[0091] In some embodiments, magnesium is a magnesium salt, such as, but not limited to, acetate, TFA salt, or formate.

[0092] In some embodiments, the magnesium salt comprises an anion (-) bonded to the Mg2+ cation via an ionic bond (e.g., but not limited to amino acid anions, acetates, carbonates, chlorides, citrates, cyanides, fluorides, nitrates, nitrites, oxides, phosphates, or sulfates).

[0093] In some embodiments, magnesium is in the form of an inorganic magnesium salt.

[0094] In some embodiments, magnesium may be magnesium oxide, magnesium citrate, magnesium glycine, magnesium diglycine, magnesium aspartate, magnesium chloride, magnesium gluconate, magnesium hydroxide, magnesium carbonate, or a mixture thereof.

[0095] In some embodiments, magnesium is magnesium oxide.

[0096] In some embodiments, the animal food compositions disclosed herein may be phosphate-restricted food compositions.

[0097] In some embodiments, the animal food composition disclosed herein may include less than about 2 g / Mcal of phosphorus.

[0098] In some embodiments, the food composition as described herein may include phosphorus from about 0.5 g / Mcal to less than about 2 g / Mcal.

[0099] In some embodiments, the food composition as described herein may 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.

[0100] In some embodiments, the food composition as described herein may include phosphorus at a concentration of about 0.6 g / Mcal to about 1.9 g / Mcal, or about 0.7 g / Mcal to about 1.7 g / Mcal, or about 0.8 g / Mcal to about 1.6 g / Mcal, or about 0.9 g / Mcal to about 1.5 g / Mcal.

[0101] In some embodiments, the food composition as described herein may include about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof and about 0.5 g / Mcal to less than about 2 g / Mcal of phosphorus.

[0102] In some embodiments, the source of phosphorus may be phosphate or its salt.

[0103] In some embodiments, phosphorus is sourced in the form of phosphates. Phosphates are particularly a source of inorganic phosphorus in food compositions.

[0104] In some embodiments, the food composition as described herein may include about 1 g / Mcal or less of inorganic phosphorus. In some specific embodiments, the food composition as described herein may 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.

[0105] Phosphates can include monophosphates, diphosphates, and / or triphosphates.

[0106] In some embodiments, the phosphate may be, but is not limited to, monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, calcium phosphate, iron phosphate, magnesium phosphate, ammonium phosphate, sodium diphosphate, potassium diphosphate, calcium diphosphate, disodium dihydrogen phosphate, trisodium diphosphate, tetrasodium diphosphate, tetrapotassium diphosphate, potassium tripolyphosphate, or sodium tripolyphosphate.

[0107] In some embodiments, the food composition as described herein may include calcium of about 1 g / Mcal to about 2 g / Mcal.

[0108] In some embodiments, the food composition described may include calcium at 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.

[0109] Illustratively, the food composition described herein may include calcium of about 1.2 g / Mcal to about 2 g / Mcal, or about 1.4 g / Mcal to about 1.8 g / Mcal, and more specifically about 1.4 g / Mcal, or about 1.5 g / Mcal, or about 1.6 g / Mcal or about 1.7 g / Mcal.

[0110] In some embodiments, the food composition as described herein may include about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof, about 0.5 g / Mcal to less than about 2 g / Mcal of phosphorus and about 1 g / Mcal to about 2 g / Mcal of calcium.

[0111] In some embodiments, the calcium source to be provided in the food composition as described herein may include meat, fish, bone meal, fish bones, eggshells, dairy products, mineral supplements, and limestone powder.

[0112] Mineral supplements that serve as a source of calcium can include calcium carbonate, calcium citrate, calcium propionate, calcium lactate, and / or calcium gluconate.

[0113] In some embodiments, the food composition as described herein may include calcium and phosphorus, such that the weight ratio of calcium to phosphorus may be less than or equal to about 2.5.

[0114] In some embodiments, the food composition as described herein may include calcium and phosphorus, such that the weight ratio of calcium to phosphorus may be characterized as 1 to 2.5, or 1 to 2.3, 1.2 to 2, or 1.3 to 1.9, or 1.3 to 1.6.

[0115] In some specific embodiments, the food composition as described herein may include calcium and phosphorus, such that the weight ratio of calcium to phosphorus may be equal to about 1.3, 1.4, 1.5 or 1.6.

[0116] In some embodiments, the food composition as described herein may include magnesium and phosphorus, such that the weight ratio of magnesium to phosphorus (Mg / P) is characterized as being from about 0.1 to about 2.2.

[0117] In some embodiments, the magnesium to phosphorus weight ratio (Mg / P) may be characterized as about 0.1 to 2.2, or 0.2 to 2.1, 0.3 to 2, or 0.3 to 1.9, or 0.4 to 1.6, or 0.4 to 1.2.

[0118] In some embodiments, the magnesium to phosphorus weight ratio (Mg / P) may be characterized as about 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1 or 1.2.

[0119] In some embodiments, the molar ratio of magnesium to phosphorus (Mg / P) in the animal food composition as disclosed herein may be characterized as being from about 0.1 to about 2.8.

[0120] In some embodiments, the molar ratio of magnesium to phosphorus (Mg / P) in the animal food composition disclosed herein may be characterized as 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.

[0121] In some embodiments, the food composition as described herein may include other nutrients and / or ingredients to provide a food composition suitable for feeding animals, particularly felines.

[0122] In some embodiments, the food composition as described herein may further include, but is not limited to, protein, fat, fiber, carbohydrates and / or vitamins.

[0123] In some embodiments, the food composition as described herein may include proteins, flavoring agents, preservatives, trace elements, coloring agents, fats, fiber, and / or vitamins. It is noteworthy that, in such embodiments, these proteins, flavoring agents, preservatives, trace elements, coloring agents, fats, fiber, and / or vitamins are complements or supplements to the ash content incorporated into the food composition as previously described.

[0124] Therefore, other nutrients and / or components should be present in adequate amounts to ensure that the animal maintains lean body mass without being toxic to the animal.

[0125] Protein sources may be selected from, but are not limited to, poultry, poultry meal, poultry by-products, mutton, mutton meal, pork, pork by-products, beef, beef by-products, white fish, milk protein, eggs, venison, soybean meal, soybean protein isolate, rice, soybean protein concentrate, corn gluten, wheat gluten, gluten, tofu, green lentils, carrots, potatoes, beets, corn gluten meal, corn protein concentrate, or combinations thereof.

[0126] Fat sources may include, but are not limited to, wheat, soybean, sunflower, safflower, rapeseed, olive, borage, flaxseed, peanut, blackcurrant seed, cottonseed, wheat germ, corn germ and oils derived from these, crude chicken fat, crude turkey fat, crude beef fat, crude duck fat, crude pork fat, crude lamb fat, fish oil or any meat, meat by-products, seafood, fish by-products, dairy products, eggs or combinations thereof.

[0127] Fiber sources may include, but are not limited to, beet pulp, guar gum, chicory root, psyllium, pectin, blueberries, cranberries, pumpkin, apples, oats, legumes, citrus fruits, barley or pea cellulose, whole wheat products, wheat and oats, corn bran, flaxseed, grapes, celery, green beans, cauliflower, potato peels, fruit peels, vegetable peels, peanut shells, soybean fiber, and combinations thereof.

[0128] In some embodiments, the described food composition may also include preservatives, trace elements, and / or colorants.

[0129] In some embodiments, the food composition as described herein may further include diluents and / or excipients.

[0130] Typically, as described herein, the total mass weight of all components in a dry matter-based food composition is 100 by weight.

[0131] The food compositions described herein may be nutritionally complete and balanced food compositions or functional foods.

[0132] As used herein, a “nutritionally complete and balanced” food composition means that the composition contains all the essential nutrients in appropriate proportions to meet the dietary needs of an animal to maintain its overall health and well-being. A nutritionally complete and balanced food composition can maintain an animal’s weight without causing significant changes in its Body Condition Score (BCS). A nutritionally complete and balanced animal food composition ensures that the animal receives all the nutrients required for optimal health, thereby minimizing the risk of nutritional deficiencies or imbalances that, over time, could lead to health problems. Specifically, a nutritionally complete and balanced food composition may contain all the known nutrients required by the intended recipient of the food composition, in appropriate amounts and proportions based on recommendations for complete and balanced pet nutrition from recognized and authoritative bodies in the field of feline nutrition, such as the Association of American Feed Control Officials (AAFCO) or the European Pet Food Industry Federation (FEDIAF). Therefore, a nutritionally adequate diet is one that can be fed as the sole food source and can sustain the animal’s life without additional food (except water).

[0133] As used herein, the term "functional complement" refers to a food composition that provides specific components essential for maintaining health in addition to basic nutrition. These food compositions may contain bioactive or bioavailable substances or ingredients, such as probiotics, amino acids, vitamins, minerals, and antioxidants, and are often found to be useful for treating diseases or maintaining normal health. Functional complement is not a nutritionally complete food composition, meaning that it does not provide companion animals with a full and balanced range of nutrients.

[0134] In some embodiments, the food composition as described herein may consist of a nutritionally complete and balanced food composition.

[0135] In some embodiments, a nutritionally complete and balanced food composition as described herein may include nutrients and / or ingredients formulated to contribute to the nutritional properties of the food composition.

[0136] Illustratively, a nutritionally complete and balanced food composition as described herein may include, but is not limited to, protein, fat, ash, fiber, carbohydrates, calcium, phosphorus, sodium, potassium, magnesium, water, vitamin D, and / or vitamin E.

[0137] In some embodiments, the food composition as described herein may consist of a wet food composition, a dry food composition, or a semi-wet food composition.

[0138] Dry food compositions can refer to food compositions with a moisture content of less than about 12% by weight.

[0139] The process for determining the moisture content of a food composition may include at least the following steps: (i) selecting a representative sample of the food composition, (ii) weighing the sample, (iii) then completely dehydrating the sample in a temperature-controlled oven (typically around 100°C) until all water has evaporated, and (iv) after cooling in a desiccator, weighing the dehydrated sample again. The moisture content is then calculated using the following formula: Moisture content (%) = [(Initial mass - Dehydrated mass) / Initial mass] × 100.

[0140] In some embodiments, the moisture content of the dry food composition as described herein may range from about 5% by weight to about 12% by weight.

[0141] In some embodiments, the moisture content of the dry food composition as described herein may be about 5% by weight, or about 6% by weight, or about 7% by weight, or about 8% by weight, or about 9% by weight, or about 10% by weight, or about 11% by weight, or about 12% by weight.

[0142] Typically, the moisture content of a dry food composition can be about 8% by weight relative to the total weight of the food composition.

[0143] In some embodiments, the dry food composition may be formed from a core and a coating to form a coated dry food composition, also known as a coated dry animal food composition.

[0144] In some embodiments, the dry food composition may be a coarsely ground food.

[0145] Semi-wet food compositions refer to food compositions with a moisture content ranging from about 12% by weight to about 50% by weight.

[0146] Typically, a semi-wet food composition is the final product of a process that allows a moisture content value between that of a dry food and a wet food. In some embodiments, the process may include a step of adding a humectant. In some embodiments, the process may include an extrusion step and a subsequent superheated steam (SHS) treatment step.

[0147] In some embodiments, the moisture content of the semi-wet food composition as described herein may be about 13% by weight, or about 14% by weight, or about 15% by weight, or about 16% by weight, or about 17% by weight, or about 18% by weight, or about 9% by weight, or about 20% by weight, or about 21% by weight, or about 22% by weight, or about 23% by weight, or about 24% by weight, or about 25% by weight, or about 26% by weight, or about 27% by weight, or about 28% by weight, or about 29% by weight, or about 30% by weight, or about 31% by weight, or about 32% by weight, or about 33% by weight, or about 34% by weight, or about 35% by weight, or about 36% by weight, or about 37% by weight, or about 38% by weight, or about 39% by weight, or about 40% by weight, or about 41% by weight, or about 42% by weight, or about 43% by weight, or about 44% by weight, or about 45% by weight, or about 46% by weight, or about 47% by weight, or about 48% by weight, or about 49% by weight.

[0148] Typically, the moisture content of a semi-wet food composition can be about 20% by weight relative to the total weight of the food composition.

[0149] A wet food composition refers to a food composition with a moisture content of more than about 50% by weight.

[0150] In some embodiments, a wet food composition refers to a food composition with a moisture content ranging from about 50% to about 90% by weight.

[0151] In some embodiments, the moisture content of the wet food composition as described herein may be about 50% by weight, or about 55% by weight, or about 60% by weight, or about 65% by weight, or about 70% by weight, or about 75% by weight, or about 80% by weight, or about 85% by weight, or about 90% by weight.

[0152] Typically, the moisture content of a wet food composition can be about 80% by weight relative to the total weight of the food composition.

[0153] Generally, wet food compositions are the final product of a process that includes a final sterilization step (rather than a drying step).

[0154] In some embodiments, the wet food composition may consist of chunks, more specifically chunks in the form of gravy.

[0155] In some embodiments, the wet food composition may consist of chunks and gravy, chunks in jelly, loaf, mousse, terrine, or bite.

[0156] Uses and methods The food compositions described herein are suitable for the treatment and / or prevention of mineral skeletal disorders in companion animals affected by or at risk of renal dysfunction, particularly those associated with hypercalcemia.

[0157] Specifically, as described in this disclosure, the food composition contains a certain amount of magnesium or a salt thereof.

[0158] This disclosure also relates to an animal food composition comprising about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium (Mg) or a salt thereof, said animal food composition being used in a method for treating and / or preventing mineral skeletal disorders, particularly mineral skeletal disorders associated with hypercalcemia, in companion animals affected by or at risk of being affected by renal dysfunction.

[0159] This disclosure also relates to a method for treating and / or preventing mineral skeletal disorders, particularly those associated with hypercalcemia, in companion animals affected by or at risk of renal dysfunction, said method comprising at least the step of providing the companion animal with a food composition comprising magnesium (Mg) or a salt thereof at about 0.3 g / Mcal to about 0.8 g / Mcal.

[0160] The purpose of this disclosure also relates to the use of magnesium (Mg) or its salts at about 0.3 g / Mcal to about 0.8 g / Mcal in the preparation of a medicament used in a method for treating and / or preventing mineraloskeletal disorders in companion animals affected by or at risk of being affected by renal dysfunction, particularly mineraloskeletal disorders associated with hypercalcemia.

[0161] In some embodiments, mineral bone disorders are associated with hypercalcemia.

[0162] In some embodiments, the companion animal is affected by kidney dysfunction.

[0163] In some cases, the companion animal is unaware that it has a kidney dysfunction.

[0164] In some embodiments, companion animals may undergo treatment for renal dysfunction. In some embodiments, the treatment is a phosphate-restricted food composition. In some embodiments, the phosphate-restricted food composition may be a food composition containing about 2 g / Mcal or less of phosphorus.

[0165] In some embodiments, renal dysfunction may be selected from kidney diseases involving the following: deterioration of renal parenchyma, loss of functional nephrons, or glomerular damage and / or deterioration.

[0166] In some embodiments, companion animals may be affected by chronic kidney disease (CKD) or at risk of being affected by CKD.

[0167] In some embodiments, companion animals may be affected by or at risk of being affected by azotemic chronic kidney disease (CKD).

[0168] In some embodiments, companion animals may be affected by or at risk of chronic kidney disease-mineral and bone disease (CKD-MBD).

[0169] In some embodiments, companion animals may be affected by or at risk of being affected by chronic kidney disease-mineral and bone disease (CKD-MBD) associated with hypercalcemia.

[0170] In some embodiments, the companion animal may further exhibit magnesium deficiency compared to a predetermined total plasma magnesium concentration, wherein the predetermined total plasma magnesium concentration is based on the average magnesium level in the blood of a control group.

[0171] Illustratively, the predetermined total plasma magnesium concentration can range from about 0.8 mmol / L to about 1.0 mmol / L. Specifically, the predetermined total plasma magnesium concentration can be about 1.0 mmol / L.

[0172] In some embodiments, the food composition for its use as described herein may be formulated and administered to the animal daily as part of the animal's diet.

[0173] In some embodiments, the food composition described herein may be fed to animals three times a day, twice a day, once a 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 a month.

[0174] In some embodiments, the food composition may be fed to the animal once or more daily. For example, but not limited to, the food composition may be administered once, twice, three times, four times, five times or more daily.

[0175] In some embodiments, the pet food composition may be fed to the animal in a constant manner, such as when the companion animal is fed a constant supply of the food composition.

[0176] In the field of pet nutrition, it is well known that those skilled in the art possess the knowledge and expertise to adjust food composition formulations to meet the specific feeding recommendations for the target animal. For example, if recommendations specify that cats should be fed once a day, twice a day, and / or only on specific days of the week, then a skilled artisan can easily modify the food composition accordingly.

[0177] In some embodiments, the food composition described herein may be provided to animals for a period of at least 3 months or longer, or 4 months or longer, or 5 months or longer, or 6 months or longer, or 7 months or longer, or 8 months or longer, or 9 months or longer, or 10 months or longer, or 11 months or longer, or 12 months or longer.

[0178] In some embodiments, the food composition described herein may be (i) fed according to a feeding schedule in which animals are exclusively fed the food composition described herein, or (ii) fed according to a feeding schedule in which animals are alternately fed the food composition described herein and another food composition for a longer period of time, such as 12 months or longer, or 18 months or longer, or 24 months or longer.

[0179] The food compositions and methods described herein can be used with a variety of companion animals, including non-human mammals such as canines and felines.

[0180] In some embodiments, the companion animal may be a cat or a dog.

[0181] In some embodiments, the companion animal is a cat.

[0182] Example Cats with chronic kidney disease (CKD) may have an increased risk of developing mineral skeletal disorders, particularly those associated with hypercalcemia.

[0183] This assay evaluated the effects of magnesium-supplemented phosphate-restricted food compositions on cats with CKD compared to standard phosphate-restricted food compositions, and on plasma levels of ionized calcium, magnesium, and FGF-23. FGF-23 is a biomarker for the progression of chronic kidney disease in cats.

[0184] A. Materials and Methods plan: The test food composition (a phosphate-restricted diet supplemented with Mg, "Mg-supplemented PRD") was compared with the control food composition (a control phosphate-restricted diet, "Control PRD").

[0185] The test group consisted of 21 cats, and the control group consisted of 23 adult cats. All cats were diagnosed with chronic kidney disease (CKD).

[0186] During the 16-week period, the cats were randomly assigned to one of two treatment groups: - Control food composition: Royal Canin Renal cat diet containing 0.15 g / Mcal magnesium (Table 1).

[0187] - Test food composition: Similar to the control food composition, except for magnesium inclusion: 0.6 g / Mcal of magnesium (supplemented by magnesium oxide).

[0188] Both diets are available in dry and wet versions. Cats are either dry-fed, wet-fed, or mixed-fed, as the formulation logic for both diets is very similar, and the assessed nutritional parameters (magnesium levels) are also similar between the dry and wet versions. The cat consumed more than 50% of the allocated food and tolerated the diet well.

[0189] Inclusion criteria for cats: - Stable azotemia, CKD, IRIS (International Renal Interest Society) stage 2 or 3 diagnosis -Stay stable on a Royal Canin adult kidney cat diet for at least 4 weeks - Plasma total magnesium concentration (tMg) < 1.0 mmol / L - Normal thyroid function (total thyroxine concentration < 40 nmol / L) Table 1: Control Food Compositions Other key nutrients: protein, fat, fiber, ash, carbohydrates, sodium, potassium, vitamin D, vitamin E Variables and parameters: The effects of dietary magnesium supplementation on magnesium and FGF-23 (fibroblast growth factor 23) plasma status were determined using the following methods: - Changes in plasma total magnesium concentration between baseline, 4–8 weeks of follow-up, and 12–16 weeks of follow-up in both treatment groups - Comparison of the average slope of the graphs of total plasma magnesium concentration versus time for each treatment group.

[0190] - Comparison of the proportion of patients with plasma total magnesium concentration < 1.0 mmol / L in each treatment group at follow-up of 4–8 weeks and 12–16 weeks compared with baseline.

[0191] - Changes in urinary magnesium excretion fraction (used as a marker of body magnesium status) between baseline, 4–8 weeks, and 12–16 weeks of follow-up in both treatment groups - Changes in plasma FGF-23 concentrations in both treatment groups between baseline, 4–8 weeks of follow-up, and 12–16 weeks of follow-up. - Comparison of the mean slope of the graphs showing plasma FGF-23 concentration versus time in each treatment group - Comparison of the proportion of each group with plasma FGF-23 concentrations > 700 pg / mL at follow-up of 4–8 weeks and 12–16 weeks compared with baseline.

[0192] The effects of oral magnesium supplementation on ionic calcium levels involved in feline CKD-MBD were determined using the following methods: Changes in ionized calcium and total calcium concentrations in the two treatment groups at baseline, 4–8 weeks, and 12–16 weeks of follow-up; comparison of the mean slope of the graphs of plasma ionized calcium and total calcium concentrations versus time for each treatment group.

[0193] method Analyze the total magnesium and total calcium concentrations in heparinized plasma samples.

[0194] Ionic calcium and venous blood gases were measured using a point-of-care analyzer.

[0195] Plasma FGF-23 concentrations were measured using validated ELISA and IRMA assays.

[0196] Baseline data of the two groups of cats were compared using an independent two-sample t-test or the Mann-Whitney U-test, and proportions were compared using a chi-square test.

[0197] The changes in all variables during the follow-up period were compared, and the effects of diet, time, and the interaction between diet and time on these changes were assessed using a linear mixed measurement model for continuous variables and a binomial-based generalized linear mixed model for categorical variables.

[0198] B. Result The rate of change in ionized calcium (iCa) concentration differed significantly between the two groups (P = 0.012). Cats fed the test food composition (PRD supplemented with Mg) showed a decreasing trend in blood iCa concentration (β, -0.023 ± 0.012 mmol / L per month; P = 0.061), while cats fed the control food composition (PRD) showed an increasing trend in blood iCa concentration (β, 0.021 ± 0.011 mmol / L per month; P = 0.078) (see [link to relevant documentation]). Figure 1 ).

[0199] Although there was no significant difference in the rate of change of plasma LnFGF23 levels between cats fed the control food composition (control PRD) and cats fed the test food composition (Mg-supplemented PRD) (p = 0.251), the plasma ln[FGF23] concentration in cats fed the control food composition increased significantly over time (β, 0.138 ± 0.049 pg / mL per month; p = 0.009), while the rate of change in cats fed the test food composition was not significantly different from 0 (β, 0.051 ± 0.056 pg / mL per month; p = 0.368) (see [link to relevant documentation]). Figure 2 ).

[0200] The rate of change in total magnesium differed significantly between the groups (P = 0.02). Cats fed the test food composition (a Mg-supplemented PRD) showed a significant increase in plasma total magnesium concentration over time (β, 0.101 ± 0.027 mmol / L per month; P < 0.001), but this was not the case for cats fed the control food composition (PRD) (β, 0.010 ± 0.025 mmol / L per month; P = 0.691). Figure 3 ).

[0201] The results of this study showed that CKD cats fed a magnesium-rich phosphate-restricted food composition for 4 months had significantly higher plasma total magnesium concentrations; compared with CKD cats fed a control food composition, these cats also showed greater stability of their plasma FGF-23 and iCa concentrations over time.

[0202] During the study period, CKD cats fed a magnesium-rich phosphate-restricted diet composition were less likely to have elevated iCa (11.8% vs. 52.9%; P = 0.026); four cats in the control group showed significant ionized hypercalcemia (blood [iCa] > 1.5 mmol / L), while no cats in the test group showed ionized hypercalcemia.

[0203] The results from this study indicate that dietary magnesium supplementation is beneficial for controlling hypercalcemia in CKD cats with low or normal total magnesium plasma concentrations.

[0204] In addition, these results indicate that while magnesium-supplemented food compositions are limited in their use of phosphate supplementation, they may delay the progression of chronic kidney disease and prevent mineral bone disorders associated with hypercalcemia.

Claims

1. An animal food composition comprising about 0.3 g / Mcal to about 0.8 g / Mcal of magnesium or a salt thereof, said animal food composition being used in a method for treating and / or preventing mineral bone disorders in companion animals affected by or at risk of being affected by renal dysfunction.

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

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

4. The animal food composition for use according to any one of claims 1 to 3, wherein the mineral skeletal disorder is a mineral skeletal 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 of being affected by renal dysfunction and suffers from magnesium deficiency compared to a predetermined total plasma magnesium concentration, wherein the predetermined total plasma magnesium concentration is based on the average magnesium level in the blood of a control group.

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

7. The animal food composition for use according to any one of claims 1 to 6, wherein the renal 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 its salt is selected from magnesium oxide, magnesium citrate, magnesium glycine, magnesium diglycine, magnesium aspartate, magnesium chloride, magnesium gluconate, magnesium hydroxide, magnesium carbonate, or mixtures thereof.

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

10. The animal food composition for use according to claim 9, wherein the source of phosphorus is selected from phosphates, diphosphates and / or tripolyphosphates.

11. An animal food composition for use according to any one of the preceding claims, wherein the food composition comprises calcium at a concentration of about 1 g / Mcal to about 2 g / Mcal.

12. The animal food composition for use according to any one of the preceding claims, wherein the weight ratio of calcium to phosphorus (Ca / P) is characterized as being less than or equal to about 2.

5.

13. The animal food composition for use according to any one of the preceding claims, wherein the weight ratio of magnesium to phosphorus (Mg / P) is characterized as being from about 0.1 to about 2.

2.

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

16. A method for treating and / or preventing mineral skeletal disorders in companion animals affected by or at risk of being affected by renal dysfunction, the method comprising at least the step of providing the companion animal with a food composition comprising magnesium (Mg) or a salt thereof at about 0.3 g / Mcal to about 0.8 g / Mcal.

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

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