FIELD OF THE INVENTION

[001] The invention encompasses compositions and methods for treating and or preventing kidney-related disorders in companion animals, wherein the compositions and methods include feeding the companion animal a composition including lipoic acid or a salt thereof.

BACKGROUND QF THE INVENTION

[002] Losses in kidney function and capacity are generally observed in aged canines and felines. Dogs of seven years or older and felines of seven years or older are considered aged and can experience this problem.

[003] The invention encompasses pet food compositions for companion animals, which have increased therapeutic and prophylactic efficacy over currently marketed companion food products for treating and/or preventing kidney disorders.

SUMMARY OF THE INVENTION

[004] The inventors have developed food compositions and methods of using the compositions for treating or preventing kidney-related disorders in animals. [005] In accordance with the invention, there is a companion pet diet meeting ordinary nutritional requirements of a companion pet and further including a sufficient amount of lipoic acid or a salt thereof to inhibit the onset of deterioration of kidney function of said companion pet.

[006] Another embodiment encompasses methods for treating or preventing kidney diseases or disorders in a companion animal, which includes feeding the animal a composition including lipoic acid or a salt thereof in an amount eftectήe to treat or present kidney damage. DETAILED DESCRIPTION OF THE INVENTION General Description

[007 J The invention encompasses methods for treating or preventing kidney disease or damage in a companion animal, which includes feeding the animal a composition of the invention, which includes lipoic acid or a salt thereof in an amount effective to treat or pre\ ent the kidney disease or damage,

[008) In certain embodiments, the effective amount is at least about 50 ppm.

[009] In certain embodiments, the effective amount is at least about 100 ppm.

[OOIOJ In certain embodiments, the effective amount is about 100 ppm to about 600 ppm.

[0011] In certain embodiments, the effective amount is about 100 ppm to about 200 ppm.

[0012] In certain embodiments, the companion animal is a dog.

[0013] In certain embodiments, the companion animal is a cat.

[0014] In certain embodiments, the composition further comprises a protein, fat, carbohydrate, fiber, and combinations thereof.

[0015] In certain embodiments, the composition is a dog food.

[0016] In certain embodiments, the composition is a cat food.

[0017] In certain embodiments, the composition is a food, a nutritional diet, a supplement, an animal treat, or a toy.

[0018] In certain embodiments, the composition is in the form of a moist food.

[0019] In certain embodiments, the composition is in the form of a dry food.

[0020] The term "companion animal" used in the present invention includes any non-human animal suitable for being kept as a pet by humans including a dog. a cat, and a rodent. The compositions of the invention are in certain embodiments for the treatment of cats and 'or dogs.

[0021 J lhe term "dog" includes tho^e dogs which are companion animals such as Canis familians. working dogs and the like. The term dog is s>nonvmous with the term canine.

_ ^* ?_ [0022 J The term "cat ^" includes those cats, which are, companion animals known as domestic cats or house cats.

[0023] The term "rodent" includes, but is not limited to. hamsters, mice, rats, guinea pigs, gerbils, rabbits, hedge hogs, ferrets, chinchillas etc.

[0024] All percentages expressed herein are b> weight of the composition on matter basis unless specifically stated otherwise.

Compositions of the Invention

[0025] One embodiment of the invention encompasses compositions for companion animals including an effective amount of lipoic acid to prevent or treat kidney-related disorders in a companion animal.

[0026] As used herein, the terms "lipoic acid or a salt thereof includes, but is not limited to, for example, alpha-lipoic acid, a racemic mixture of lipoic acids, a lipoate salt, ester, amide or derivative thereof, for example as described in U.S. patent number 5,621,117. In various embodiments, the lipoic acid can be administered in a composition comprising a wet or dry food composition, which may be in the form of a moist food, dry food, supplement or treat. The lipoic acid may be incorporated therein or on the surface of any food composition, such as, by spraying or precipitation thereon or may be added to the diet by way of snack, supplement, treat or in the liquid portion of the diet such as water or another fluid. The lipoic acid may be administered as a powder, solid or as a liquid including a gel. An important aspect is that the animal be provided an effective amount of the lipoic acid to provide a positive effect. Typically, the source of lipoic acid is present in the composition in an amount up to an amount which remains non-toxic to the animal.

[0027] The quantit) of alpha-lipoic acid can vary from at least about 25 ppm. about 50 ppm, about 100 ppm, about 200 ppm. about 300 ppm. about 500 ppm, about 700 ppm. about 900 ppm. about 1 100 ppm. about 1200 ppm, about 1400 ppm, about 1600 ppm. about 1800 ppm. about 2000 ppm, about 2200 ppm. about 2400 ppro, about 2600 ppm. about 2800 ppm, about 3000 ppm. or about 3500 ppm. In \arious embodiments, the range of lipoic acid that can be administered to dogs is about 150 ppm to about 4500 ppm. In \arious embodiments, the range of lipoic acid that can be administered to cats is about 65 ppm to about 2600 ppm. In certain illustrative embodiments, quantities can \ ary from about 100 ppm to an amount which remains nontoxic to the pet. In other embodiments, a range is from about

100 ppm to about 200 ppm.

[0028] In various embodiments, a food composition comprising lipoic acid provides a substantially nutritionally complete diet for the intended recipient animal. A "nutritional!} complete diet" is a diet that includes sufficient nutrients for maintenance of normal health of a healthy animal on the diet.

[00291 The compositions of the invention include lipoic acid or salt thereof in an amount effective to treat or prevent kidney-related disorders in a companion animal.

[0030] The lipoic acid or salt thereof is present at a concentration that is not deleterious to the intended animal's health. Thus, for example, the lipoic acid or salt thereof is present at a concentration that does not cause undesirable or toxic effects.

[0031] The composition can be a liquid or a solid food. When the composition is a liquid, the lipoic acid or salt thereof can be admixed with other components. Where the composition is solid, the lipoic acid may be coated on the composition, incorporated into the composition, or both.

[0032] In various embodiments, the lipoic acid or salt thereof may be added to the animal ^' s food. In various embodiments, the lipoic acid or salt thereof may be added to the animal's food by a compounder or manufacturer at a site or by an animal ^' s caregiver prior to feeding the animal. In various embodiments, the lipoic acid or salt thereof mav be added during the processing of an animal's food, such as during and' or after mixing of other components of the composition that is then packaged and made available to consumers. Such processing may include extrusion, canning, baking, and the like or an} other method or process of producing pet foods that is known in the art. In various embodiments, the lipoic acid or salt thereof mav be contributed by a natural source like an animal or plant component, or the lipoic acid or salt thereof be contributed by a synthetical!} derived source, or the lipoic acid or salt thereof ma\ be contributed bv a mixture of natural and svnthetic sources. 10033] The compositions in addition to lipoic acid or a salt thereof include at least one component suitable for consumption by a companion animal including, but not limited to, fats, carbohydrates, proteins, libers, nutritional balancing agents such as vitamins, minerals, and trace elements, and mixtures thereof. One of ordinary skill in the art can select the amount and type of food ingredients for a typical food based upon the dietary requirements of the animal, for example, the animal's species, age. size, weight, health, and function. [0034] The food ingredient part of the food composition can include up to about 100% of any particular food ingredient or can include a mixture of food ingredients in proportions. In certain embodiments, the food composition includes a combination of food ingredients in amounts of about 0 wt. % to about 50 wt. % fat, about 0 wt. % to about 75 wt. % carbohydrate, about 0 wt. % to about 95 wt. % protein, about 0 wt. % to about 40 wt. % dietary fiber, and about 0 wt. % to about 15 wt. % of one or more nutritional balancing agents. [0035] In certain embodiments, the fat and carbohydrate food ingredient is obtained from a variety of sources such as animal fat, fish oil, vegetable oil. meat, meat by-products, grains, other animal or plant sources, and mixtures thereof. Grains include wheat, corn, barley, and rice.

[0036] In certain embodiments, the protein food ingredient is obtained from a variety sources such as plants, animals, or both. Animal protein includes meat, meat by-products, dairy, and eggs. Meats include the Ωesh from poultry, fish, and animals such as cattle, swine, sheep, goats, and the like, meat by-products include lungs, kidneys, brain, livers, stomachs, and intestines. The protein food ingredient may also be free amino acids and/or peptides. Preferably, the protein food ingredient includes meat, a meat by-product, dairy products, or eggs.

[0037] In certain embodiments, the fiber food ingredient is obtained from a varietj. of sources such as vegetable fiber sources, for example, cellulose, beet pulp, peanut hulls, and soy fiber. [0038] In certain embodiments, the nutritional balancing agents are obtained from a variety of sources known io skilled artisans, for example, vitamin and mineral supplements and food ingredients. Vitamins and minerals can be included in amounts required to avoid deficiency and maintain health. These amounts are rcadilv a\ ailable in the art. The National Research Council (Ts ¹ RC) pro\ides recommended amounts of such nutrients for farm animals. Sec. e.g., Nutrient Requirements of Swine (10th Rev. Ed., Natl Academy Press, Wash. D. C. 1998), Nutrient Requirements of Poultry (9th Re\. Ed.. Natl Acadeim Press, Wash. D.C.. 1994). Nutrient Requirements of Horses (5th Rev. Ed., Natl Aeaderm Press. Wash. D. C. 1989). The American Feed Control Officials (ΛΛFCO) pro\ ides recommended amounts of such nutrients for dogs and cats. See American Feed Control Officials. Inc.. Official publication, pp. 129-137 (2004). Vitamins generally useful as food additives include \itamin A, vitamin Bl . vitamin B2, vitamin B6. vitamin B 12, vitamin D, biotin, vitamin K, folic acid, inositol, niacin, and pantothenic acid. Minerals and trace elements useful as food additives include calcium, phosphorus, sodium, potassium, magnesium, copper, zinc, chloride, iron, selenium, iodine, and iron.

[0039] In certain embodiments, the food compositions may contain additional ingredients such as vitamins, minerals, fillers, palatability enhancers, binding agents, flavors, stabilizers, emulsi tiers, sweeteners, colorants, buffers, salts, coatings, and the like known to skilled artisans. Stabilizers include substances that tend to increase the shelf life of the composition such as preservatives, synergists and sequestrants, packaging gases, stabilizers, emulsifiers, thickeners, gelling agents, and humectants. Examples of emulsifiers and/or thickening agents include gelatin, cellulose ethers, starch, starch esters, starch ethers, and modified starches. Specific amounts for each composition component, food ingredient, and other ingredients will depend on a variety of factors such as the particular components and ingredients included in the composition; the species of animal; the animal's age. body weight, general health, sex. and diet; the animal's consumption rate; the tvpe of disease or condition being treated; and the like. Therefore, the component and ingredient amounts ma\ \ary widely and may deviate from the preferred proportions described herein.

[004OJ In one illustrative embodiment, the composition mav. for example, in addition to lipoic acid or a salt thereof also include at least one of the following ^*

(a.) about O ⁰ O to about 75% carbohydrate, fb) about 2% to about 50% fat.

(c) about 0% to about 40% dietarv fiber, and

_t>- (d) about 0% to about 15% of one or more nutritional balancing agents. [00411 The diet fed to the adult companion pet, for example, canine and feline is the standard norma! diet fed to an animal of that age. Below is a typical diet for a canine of 1 to 6 years of age.

Table 1: Illustrative Companion Animal Pet Food Composition

Ingredient Target

Protein (% of dry matter) 23

Fat (% of dry matter) 15

Phosphorous (% of dry matter)

Sodium (% of dry matter) 0.3

[0042] The compositions can contain additional ingredients intended to maintain or improve the health of the animal, for example, supplements, medications, herbs, holistic drugs and compositions, and the like.

[0043] The composition of the invention may include one or more additional ingredients to prevent or treat one or more diseases or conditions.

[0044] The component in the diet, which accomplishes this, is an antioxidant or mixture thereof. An antioxidant is a material that quenches a free radical. Examples of such materials include foods such as Ginkgo Biloba. citrus pulp, grape pomace, tomato pomace, carrot and spinach, all preferably dried as well as various other materials such as beta-carotene, selenium, coenzyme QlO (ubiquinone), lutein, tocotrienols. soy isoflavones, S- adenosylmethionine, glutathione, taurine. N-acetylcysteine, Vitamin E, Vitamin C. alpha- lipoic acid, 1-camitine and the like. Vitamin E can be administered as a tocopherol or a mixture of tocopherols and various derivatives thereof such as esters like vitamin E acetate, succinate, paimitate, and the like. The alpha form is preferable but beta, gamma and delta fomis can be included, lhe d form is preferable but racemic mixtures are acceptable, i'he forms and derivatives will function in a Vitamin E like activity after ingestion b> the pet. Vitamin C can be administered in this diet as ascorbic acid and its various derivatives thereof such as calcium phosphate salts, choicstcrj l salt. 2 -monophosphate, and the like which will function in a \itamin C like activity after ingesting by the pel. They can be in any form such as liquid, semisolid, solid and heat stable form. Alpha-lipoic acid can be administered into the diet as alpha lipoic acid or as a lipoate derivative as in U.S. Pat. No. 5.621,1 17, raceniic mixtures, salts, esters or amides thereof. L-earnitine can be administered in the diet and derivatives of carnitine such as the salts such as the hydrochloride, fumarate and succinates, as well as acetylated carnitine, and the like can be used.

[0045] The quantities administered in the diet, all as wt % (dry matter basis) of the diet, are calculated as the active material, per se, that is measured as free material. The maximum amounts employed should not bring about toxicity. At least about 100 ppm or at least about 150 ppm of Vitamin E can be used. A preferred range of about 500 to about 1.000 ppm can be employed. Although not necessary, a maximum of about 2000 ppm or about 1500 ppm is generally not exceeded. With respect to Vitamin C at least about 50 ppm is used, desirably at least about 75 ppm and more desirably at least about 100 ppm. A non-toxic maximum can be employed. The quantity of alpha-lipoic acid can vary from at least about 25, desirably at least about 50 ppm, more desirably about 100 ppm. Maximum quantities can vary from about 100 ppm to an amount which remains non-toxic to the pet. A preferred range is from about 100 ppm to about 200 ppm. For 1-carnitine about 50 ppm, desirably about 200 ppm. more desirably about 300 ppm for canines are a useful minimum. For felines, slightly higher minim urns of 1-carnitine can be employed such as about 100 ppm, 200 ppm, and 500 ppm. A non-toxic maximum quantity can be employed, for example, less than about 5,000 ppm. For canines, lower quantities can be employed, for example, less than about 5,000 ppm. For canines, a preferred range is about 200 ppm to about 400 ppm. For felines, a preferred range is about 400 ppm to about 600 ppm. Beta-carotene at about 1-15 ppm can be employed. Selenium at about 0.1 up to about 5 ppm can be employed. Lutein at least about 5 ppm can be employed. Tocotrienols at least about 25 ppm can be employed. Coenzyme QlO at least about 25 ppm can be employed, S-adenosylmethionine at least about 50 ppm can be employed. Taurine at least about 1000 ppm can be employed. Soy ones at least about 25 ppm can be used. N-aeetylcysteiiie at least about 50 ppm can be used. Glutathione at least about 50 ppm can be used. Gingko Biloba at least 50 ppm of extract can be used. [0046] The following are raw ingredients that are high in ORAC (Oxygen radical absorbing capacity) content: Spinach pomace. Tomato pomace. Citrus Pulp, Grape Pomace, Carrot granules. Broccoli, Green tea. Ginkgo Biloba and Corn gluten meal. 10047] When added to the diet as 1% inclusions (for a total of 5% substitution for a low ORAC ingredient such as corn) they increased the ORAC content of the overall diet and increased the ORAC content of the plasma of the animals which ate the diet containing these components. Preferably, any ingredient with an ORAC content >25 μmole of Trolox equivalents per gram of dry matter could be used if added at 1% combination with four other 1% ingredients for a total of 5% addition to the diet. In certain embodiments, the compositions further include an effective amount of at least one substance selected from the group consisting of glucosamine, chondroitin. chondroitin sulfate, methylsulfonylnicthane ("MSM ^* '). creatine, antioxidants, Perna canuHculata, omega-3 fatty acids, omega-ό fatty acids and mixtures thereof.

[0048] In various embodiments, a supplement including an effective amount of lipoic acid or a salt thereof further includes an effective amount of at least one substance including aspirin, antiinflammatories such as ibuprofen, COX-2 inhibitors, and other medicinal and pharmaceutical compositions and combinations thereof. Supplements include, but are not limited to, a feed used with another feed to improve the nutritive balance or performance of the total. Supplements include compositions that are fed undiluted as a supplement to other feeds, offered free choice with other parts of an animal's ration that are separately available, or diluted and mixed with an animal's regular feed to produce a complete feed. The AAFCO, for example, provides a discussion relating to supplements in the American Feed Control Officials. Inc. Official Publication, p. 220 (2003). Supplements may be in various forms including, for example, powders, liquids, syrups, pills, and encapsulated compositions. (0049] In certain embodiments, the composition can be a treat. Treats include compositions that are gήen to an animal to entice the animal to eat during a non-meal lime, for example, clog bones for canines. Treats may be nutritional wherein the composition includes one or more nutrients and ma\ ha\e a food-like composition. Non-nutritional treats encompass am other treats that are non-toxic. ^' I he composition or components are coated onto the treat,

-Q. incorporated into the treat, or both. ^' 1 rcats of the invention can be prepared by an extrusion or baking process similar to those used for dry food. Other processes also nia} be used to either coat the composition on the exterior of existing treat forms or inject the composition into an existing treat form.

[0050] In certain embodiments, the composition can be a toy . Toys include chew able toys such as artificial bones. The lipoic acid or a salt thereof can form a coating on the surface of the toy or on the surface of a component of the toy, be incorporated partially or fully throughout the toy, or both. In one embodiment, the lipoic acid or a salt thereof is orally accessible by the intended user. There are a wide range of suitable toys currently marketed, for example, U.S. Pat. No. 5,339,771 , U.S. Pat. No. 5,419,283, and references disclosed therein. This invention provides both partially consumable toys, for example, toys including plastic components, and fully consumable toys, for example, rawhides and various artificial bones. The invention preferably provides toys for use by a dog or a cat.

Preparation of the Compositions of the Invention

[0051 J The compositions of the invention may be prepared in a canned or wet form using conventional food preparation processes known to skilled artisans. Typically, ground animal proteinaceous tissues are mixed with the other ingredients such as fish oils, cereal grains, balancing ingredients, special purpose additives (e.g., vitamin and mineral mixtures, inorganic salts, cellulose and beet pulp, bulking agents, and the like) and water in amounts sufficient for processing. These ingredients arc mixed in a vessel suitable for heating while blending the components. Heating of the mixture is effected using any suitable manner, for example, direct steam injection or using a vessel fitted with a heat exchanger. Following the addition of the last ingredient, the mixture is heated to a temperature of about 50 ⁰ F to about 212 ⁰ F. Temperatures outside this range are acceptable but may be commercially impractical without use of other processing aids. W hen heated to the appropriate temperature, the material will typically be in the form of a thick liquid. The thick liquid is filled into cans. A lid is applied, and the container is hermetically sealed, fhe sealed can is then placed into conventional equipment designed to sterili/e the contents. Sterilization is usually accomplished by heating

-lυ- to temperatures of greater than about 230 ⁰ F for an appropriate time depending on the temperature used, the composition, and similar factors. The compositions of the present imention can be added to the food compositions before, during, or after preparation. |0052J Food compositions may be prepared in a dry form using conventional processes known to skilled artisans. Typically, dry ingredients such as animal protein, plant protein, grains, and the like are ground and mixed together. Moist or liquid ingredients, including fats, oils, animal protein, water, and the like are then added to and mixed with the dry mix. The mixture is then processed into kibbles or similar dry pieces. Kibble is often formed using an extrusion process in which the mixture of dry and wet ingredients is subjected to mechanical work at a high pressure and temperature and forced through small openings and cut off into kibble by a rotating knife. The wet kibble is then dried and optionally coated with one or more topical coatings such as flavours, fats, oils, powders, and the like. Kibble also can be made from the dough using a baking process, rather than extrusion, wherein the dough is placed into a moid before dry-heat processing. The food compositions can be in the form of a treat using an extrusion or baking process similar to those described above for dry food or a toy such as those disclosed in U.S. Patent Nos. 5,339,771 and 5,419,283. The compositions of the present invention can be added to the food compositions before, during, or after preparation.

Methods of Treating or Presenting Disorders with Compositions of the Invention

[0053] The invention encompasses methods of treating or preventing certain disorders by administering a therapeutically or prophylactically effective amount of a composition including lipoic acid or a salt thereof to a companion animal in need thereof.

[0054] Adding quantities of an antioxidant or mixture thereof to the companion adult pet diet can bring about delay of the onset of demonstrative changes in kidney function in a pet. The term, adult, is intended to mean, in general, a canine of at least 1 to 6 years and a feline of at least 1 to 6 years. An aged dog or cat is 7 years and above.

[0055 J The imentors have succeeded in accomplishing delaying the onset of kidney deterioration. By using the diet of their invention in companion pets it can be shown that a pet's kidney function can be maintained for a longer period of time. Essential!) the deterioration of kidnej function can be stopped or delaved.

|0Θ56] Another embodiment of the invention encompasses methods for treating or preventing kidney disease in a companion animal. In one embodiment, the invention encompasses methods of treating or preventing kidney disease in a companion animal, which includes feeding the animal a composition including lipoic acid or a salt thereof in an amount effective to treat or pre\ent the kidney damage. In another embodiment, the invention encompasses the use of a composition including lipoic acid or a salt thereof for the manufacture of a medicament for the treatment or prevention of kidney damage in a companion animal. In certain embodiments, the invention encompasses administering the composition including lipoic acid or a salt thereof to companion animals susceptible to or suffering from kidney disease or administering the compositions to animals experiencing a decline in kidney function, particularly a decline due to aging. The composition may also be fed to companion animals that are healthy in order to maintain healthy kidney functions and/or prevent kidney disease. The invention is based upon the discover)' that the presence of lipoic acid or a salt thereof in an animal's diet enhances or improves kidney function. Without being bound b\ theory, it is believed that the improvement results from decreased presence of oxygen species in the blood due to the presence of lipoic acid or a salt thereof, which is an antioxidant. As shown in the results in Example 1, dogs fed lipoic acid or a salt thereof had reduced blood urea nitrogen and creatinine compared to similar foods containing fish oil. [0057] As used herein, "enhancing or impro\ ing kidney function" means increasing the kidney's ability to remove waste or toxins from an animal ^' s blood as compared to an earlier time. Generally, as animals age, there is a decrease in the total glomerular filtration caused by a declining ability of the kidneys to adequate!) filter urine. It is believed that this decrease in kidney function is caused by a decrease in nephron number and function. Generally, any of several blood indices may be used to determine kidney function, particularly the SCΛ erity of decrease in kidney function or renal disease. Among these indices is serum urea nitrogen (SLN). SUN levels in the blood of an animal increase when the animal suffers from renal failure because damage to the kidney lessens the kidney ^* s ability to adequately filter urea, a

.! ?. waste product. Kidtie} function can also be monitored bj measuring the amount of creatinine present in the animal's blood. Creatinine is a break -down product of creatine phosphate in muscle and is filtered the kidney. Therefore, if the kidney is not functioning proper!}, the blood level of creatinine rises. Therefore, the level of creatinine in the blood ma} be used to calculate creatinine clearance. The measurement of both SUN levels and creatinine levels in the blood provides a good indication of kidney function. Kidney function can also be measured via the monitoring of glomerular filtration rate (GFR). The greater an animal ^' s GFR. the better the kidneys are at removing waste and, therefore, functioning. GFR can be measured in a number of ways, including the use of an iohexol clearance test. Per this test, the intended animal first fasts for twelve or more hours. Then, iohexol, a radiographic contrast agent, is injected into the blood via an intravenous catheter. At 2, 3. and 4 hours after administration of iohexol. a minimum of 4 ml of blood (at least 1.2 ml serum) is obtained and tested. The rate at which iohexol in the blood is decreasing indicates the level at which the kidney is functioning. The overall functioning of the animal's kidneys can be measured a comparison of that animal "s GFR at one point in time versus the animal ^' s GFR at a later point in time.

[0058] An exemplary diagnostic method for assessing kidney function includes measurement of albumin content of urine. Elevated albumin levels in urine, in particular the slightly to moderately elevated levels known as microalbuminuria, are an indicator of a decline in kidney function as occurs, for example, in incipient kidney disease.

[0059] In the methods according to the invention, a companion animal is fed the composition of the invention including lipoic acid or a salt thereof in an amount effective to treat or prevent the kidney damage. The animal is maintained on a diet including the composition for a sufficient period to improve kidney function, for example, until the animal shows a reduced serum nitrogen level and'or creatinine level and/or improved GFR. The method is particular!} applicable to animals that are susceptible or suffering from kidiiej disease caused by aging, xenobiotics. or pathogens.

{0060] The inv ention is not limited to the particular methodology , protocols, and reagents described herein because the} may vary . Further, the terminology used herein is for the

, 1 i- purpose of describing particular embodiments only and is not intended to limit the scope of the present im enlion. As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise. Similarh , the words "include ^" , "includes", and "including ^" ' are to be interpreted inclusύelj rather than exclusively . Unless defined otherwise, all technical and scientific terms and an> acron}ms used herein have the same meanings as common!} understood by one of ordinary skill in the art in the field of the invention. Although any compositions, methods, articles of manufacture, or other means or materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred compositions, methods, articles of manufacture, or other means or materials arc described herein.

[0061] xAll patents, patent applications, publications, and other references cited or referred to herein are incorporated herein by reference to the extent allowed by law. The discussion of those references is intended merely to summarize the assertions made therein. No admission is made that any such patents, patent applications, publications or references, or any portion thereof, is relevant prior art for the present invention and the right to challenge the accuracy and pertinence of such patents, patent applications, publications, and other references is specifically reserved.

EXAMPLES

[0062] This invention can be further illustrated by the following examples of preferred embodiments thereof, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the invention unless otherwise specifically indicated.

EXAMPLE 1

[0063] Table 2 illustrates the ingredients in an illustrative pet food composition of the invention.

Table 2. Ingredients _* used to make composition

Jngredients

[0064] Table 3 illustrates kidnej makers measured in blood samples for dogs after being fed a control diet compared with dogs fed a pet food including lipoic acid for 90 da>s. As illustrated in Table 3, dogs fed a control plus lipoic acid displaced decreased kidnev markers after 90 s.

tble 3. Kidnev markers measured in the blocd in dogs at da\ 90 fed three foods

Probability. ? <

Lpgrade i Lpgrade

Upgrade VS lipoic \s etabohte Control Lf )grade 1 ~hp_oie ' SE Control control ine_sτjeufic gra\ ity 1.026 1 .025 I 027 0 005 0.84 0 _ 58 0 73 ood Urea Nitrogen , 16 42 2.76 , 22.84 2 472 0.02 OJl

.1 v rcatinine i i lood Urea Nitrogen,

11 71 ¹ 14 31 13 54 ¹ 1 525 0 .10 0.62 ) 0 23 reatimne, mg/dL J_Jλ6£_ 0. 61 0.024 0 .03 0.01 0 \ alues used as a co\ ariate in the analysis. Control refers to standard AAFCO log food, Jpgrade refers to a low fat. reducec calorie, high fiber pet food

[0065] Table 4 illustrates kidney makers measured in blood samples for dogs after being fed five different pet foods for 180 da>s.

DayJ) values used as a co\ ariate in the analysis.

[0066] Table 5 illustrates change in metabolite measured m blood samples for dogs after being fed a control diet compared with dogs fed a pet food including lipoic acid for 30 As illustrated in Table 5, dogs fed a control plus lipoie acid displayed decreased kidnev markers after 30 days

Table 5. Fold change in metabolites measured in the blood in dogs at da} 30 fed

Probdbilm , P ^«

Metabolite ___Control Upgrade v s L pgrade \_s I pgrade _^ Upgrade _j

[0067] The invention is not to be limited in scope by the specific embodiments disclosed in the examples, which are intended as illustrations of a few aspects of the invention, and any embodiments, which are functionally equivalent, are within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art and are intended to fall within the appended claims. [0068] All patents, patent applications, publications, and other references cited or referred to herein are incorporated herein by reference to the extent allowed by law. The discussion of those references is intended merely to summarize the assertions made therein. No admission is made that any such patents, patent applications, publications or references, or any portion thereof, is relevant prior art for the present invention and the right to challenge the accuracy and pertinence of such patents, patent applications, publications, and other references is specifically reserved.