Nutrition and Urolithiasis Joe Bartges, DVM, PhD, DACVIM, DACVN Claudia Kirk, DVM, PhD, DACVIM, DACVN, Knoxville, TN UROLITH FORMATION Urolithiasis is a common cause of disease in dogs and cats and affects the upper and lower urinary tracts. Medical dissolution and preventative protocols are available for urolithiasis and dietary modification is an important part. Urolith formation occurs when urine is oversatured with the calculogenic minerals. Risk factors include breed, gender, age, diet, metabolic status, and chemical composition of urine. Although microscopic crystalluria likely precedes uralith formation, not all animals with crystallura form uroliths and urolths can be present without crystalluria. Once urolith formation has been initiated, the urolith nidus must be retained within the urinary tract, and the urinary environment must favor continued precipitation of minerals, aggregation of these ‘minerals, and growth of the roth. Alterations in balance between urine concentrations of calculogenic substances and calculogenic inhibitors result in initiation and growth of urolits.” STRUVITE ‘Struvite is magnesium ammonium phosphate hexahydrate and can occur as a consequence of a bacterial urinary tract infection (infection induced struvite) or without a urinary tract infection (sterile struvite. infection-induced struvite occurs commonly in dogs and occasionally in cats, while sterile struvite occurs commonly in cats and rarely in dogs** Infection-induced struvite Infection-induced struvite uroliths form as a consequence of a bacterial urinary tract infection with a microbe that produces urease; Staphylococcus spp occur most commonly. Microbial urease results in oversatuation of urine with struvite calculogenic substances by metabolizing urea to ammonia, producing alkali, altering the ionization state of phosphorous, and increasing urinary inflammatory proteins and cells that are incorporated into the urolith. Infection-induced struvite uroliths can be dissolved by ‘administering an appropriate antimicrobial agent and feeding a diet to decrease urine to an undersaturated state with regards to struvite, Such a diet is, in comparison with adult maintenance diets, relatively lower in protein resulting in less available urinary urea for microbial urease metabolism, lower in phosphorous, lower in magnesium, acidifying, and diuresing:” The antimicrobial agent ‘must be administered until dissolution is documented to occur. Average time of dissolution is approximately 2 months. Prevention of infection induced struvite urolths is accomplished by preventing, controlling and treating bacterial urinary tract infections. Although diets formulated to decrease urinary saturation with struvite are available, they have limited usefulness and indication because its the infection with a urease-producing microbe that causes infection-induced struvite urolth formation. Sterile struvite Stefile struvite urolths form typically in 1-10 year old cats, although they have been reported to occur rarely in dogs” Sterile struvite Luroliths form because of dietary influence on urine composition as well as innate risks for urolith formation. Experimentally, ‘magnesium phosphate and struvite uroiths formed in healthy cats consuming calculogenic diets containing 0.15 to 1.0% magne- sium (dry matter basis)” These data are difficult to interpret, however, because the amount of magnesium consumption by cats in these studies may be different in than cats that spontaneously form sterile struvite urolths consuming commercial diets due to differences in caloric density, palatability, and digestibility. The influence of magnesium on struvite formation depends on urine pH* and influence of ions, minerals, and other components in urine.” Alkalura is associated with increased risk for struvite formation." Ina clinical study including 20 cats with naturally occuring struvite urocystoliths and no detectable bacterial urinary tract infection, the mean urinary pH atthe time of diagnosis was 69 + 0.4. An additional factor is water intake and urine volume. Consumption of increased quantities of water may result in lowering concentrations of clculogenic substances in urine, thus, decreasing risk of Lrolith formation.’* Consumption of small quantities of food frequently rather than one or two large meals per day is associated \with production of more acidic urine and 2 lesser degree of struvite cstalluria by cats.” Sterile struvite uroliths can be dissolved by feeding a diet that is restricted in magnesium, phosphorous, and protein, and that induces aciduria relative to adult maintenance ‘at foods.” In a dinical study including 22 cats with sterile struvite urocystoiths, urocystoliths dissolved in 20 cats in a mean of 36.2 + 266 days (range, 14 to 141 days). The cats were fed a high-moisture (canned), caloricaly dense diet containing 0.058% ‘magnesium (dry matter basis) and increased sodium chloride (0.79% dry matter basis) that induced a urine pH of approximately 6.0. Prevention of stele struvite uroliths involves inducing a urine pH less than approximately 6.5, increasing urine volume, and. decreasing excretion of magnesium, ammonium, and phosphorous. CALCIUM OXALATE Calcium oxalate urolith formation occurs when urine is oversaturated with calcium and oxalate’ In addition to these alterations in activities of ions, large molecular weight proteins occurring in urine, such as nephrocalcin, uropontin, and Tamm-Horsfal ‘mucoprotein, influence calcium oxalate formation." Hypercalciuria isa significant risk factor, but not necessarily the cause of calcium oxalate urolth formation in human beings, dogs, and cats.” Hypercalciuria can result from excessive intestinal absorption ‘of calcium (Gi hyperabsorption), impaired renal reabsorption of calcium (renal leak), and/or excessive skeletal mobilization of calcium (tesorptive). Hypercalciuria has not been well defined in normocalcemic cats with calcium oxalate urolths but is thought to occur, Hypercalcemia results in hypercaliuria, which may promote calcium oxalate formation. Approximately 5% of dogs and 3546 of cats with calcium oxalate uroliths are hypercalcemic; primary hyperparathyroidism is the most common cause in dogs and idiopathic hypercalcemia is the most common cause in cats. continued on ret pogeyee Nutrition and Urolithia: Joe Bartges, DVM, PhD, DACVIM, DACVN Claudia Kirk, DVM, PhD, DACVIM, DACVN, Knoxville, TN ‘line Prctior™ contd fom prvi pe ‘Metabolic acidosis promotes hypercalciuria by promoting bone tumover (release of calcium with buffers from bone), increasing serum ionized calcium concentration resulting in increased urinary calcium excretion, and decreased renal tubular reabsorpt ‘calcium. Consumption of diets supplemented with the urinary acidifier ammonium chloride by cats has been associated with increased urinary calcium excretion.” Significant aciduria (urine pH < 6.2) may represent a isk factor for calcium oxalate formation because of acidemia and hypercalciuria In addition, acidic urine alters function and concentration of cystal inhibitors. Low urine pH decreases urinary citrate concentration by increasing renal proximal tubular citrate reabsorption. Acidic urine is known to impair function of macromolecular protein inhibitors. inhibitors, such as citrate, magnesium, and pyrophosphate, form soluble salts with calcium or oxalic acid and reduce availabilty of calcium or oxalic acid for precipitation. Other inhibitors, such as Tamm-Horsfall lycoprotein and nephrocalcn, interfere with the ability of calcium and oxalic acid to combine minimizing crystal formation, ‘aggregation, and growth. Oxalic acid is a metabolic end product of ascorbic acid (vitamin C) and several amino acids, such as alycine and serine, derived from dietary sources. Oxalic acid forms soluble salts with sodium and potassium ions, but a relatively insoluble salt with calcium ions. Therefore, any increased urinary concentration of oxalic acid may promote calcium oxalate formation. Decreased urine volume result in increased calcium and oxalic acid saturation and an increased risk for uroth formation, ‘Medical protocols that will promote dissolution of calcium oxalate uroliths are not curently available; therefore, uroliths must be removed physically, either surgically or by voiding urohydropropulsion.” Nutritional and/or medical protocols should be considered to minimize urolth recurrence or prevent further growth of urolths remaining in the urinary tract. Goals of dietary prevention include: 1) reducing urine calcium and oxalate concentration, 2) promoting high concentrations and activity of urolth inhibitors, 3) reduce urine acidity, and 4) promote dilute urine. Dietary modification for prevention of calcium oxalate uroliths in dogs and cats includes inducing diuresis, restricting protein, promoting alkaluria, and restricting calcium. Fr cats with idiopathic hypercalcemia, feeding a higher fiber diet with supplemental potassium citrate may be effective” Increasing urine volume is a mainstay of preventative therapy for calcium oxalate urolithiasis in human beings. By increasing water intake, urinary concentrations of calculogenic minerals are reduced. In addition, larger urine volumes typically increase urine transit time and voiding frequency, thereby reducing retention time for crystal formation and growth. Feeding cats a canned food is the most practical means of increasing water intake and lowering calcium oxalate urine saturation. Solubilty of calcium oxalate in urine is minimally influenced by pH; however, epidemiologic studies consistently identity ‘acidifying diets among the most prominent risk factors for calcium oxalate urolithiasis*~* Furthermore, aciduria promotes hhypocitratura, and functional impairment of endogenous urolith inhibitors Potassium citrate is often included in diets designed {or calcium oxalate prevention. In urine, citric acid combines with calcium to form soluble complexes, thereby reducing ionic calcium concentration. Citric acid also directly inhibits nucleation of calcium and oxalate crystals. Consumption of high levels of sodium may ‘augment renal calcium excretion in human beings. Recent studies in healthy cats and dogs did not find increased urine calcium excretion in response high dietary salt intake" Urinary magnesium forms complexes with oxalic acid, reducing the amount of oxalic acid available to form calcium oxalate. Studies in cats associate low dietary magnesium with calcium oxalate risk. There are currently, several commercial diets available for dogs and cats that meet these nutritional recommendations. URATE Uric acd is one of several biodegradation products of purine nucleotide metabolism.” In most dogs and cats, allantoin is the major ‘metabolic end product: its the most soluble of the purine metabolic products excreted in urine. Ammonium urate is the monobasic ammonium salt of uric acid, and it is the most common form of naturally occurring purine uroliths observed to occur in dogs and ‘as Urate urliths may occur as a consequence of liver disease, specially @ portal vascular anomaly, or without the presence of liver disease, termed idiopathic urate urolithiasis. Uae uroliths occurring in association with portovascular anomalies are most ‘commonly composed of ammonium urate, and often diagnosed before 1 year of age ‘There apparently have been few studies ofthe biological behavior of ammonium urate uroliths in dogs with portal vascular anomalies” and none in cats. iis logical to hypothesize that elimination of hyperuricuia and reduction of urine ammonium concentration following surgical correction of anomalous shunts would result in spontaneous dissolution of uroliths composed primarily of ammonium urate. Appropriate dlinical studies are needed to prove or disprove this hypothesis. Dissolution of urate Luroliths in dogs without iver disease is possible using a protein-resticted, alkalinizing diet and allopurinol, although the success rate is approximately 40%.” Restricting dietary protein results in lower concentrations of purine precursors that are converted to uric ‘acid. inducing alkaluria increases solubility of ammonium urate. A similar strategy is used for prevention. Although no studies have been performed evaluating the efficacy or safety of medical dissolution of urate uroliths in cats with idiopathic urate urolithasis, we have successfully dissolved urate uroliths in cats using a low protein diet and allopurinol. Until further studies are performed to confirm the safety and efficacy of medical dissolution, surgical removal remains the treatment of choice for urate urolths in cats. Prevention of urate urolith recurrence in cats has been > 90% when using a protein restricted, alkalinizing det. continued on ne poseSW, os pgp etter ae : . Nutrition and Urolithiasi = 2 Joe Bartges, DVM, PhD, DACVIM, DACN & (Claudia Kirk, DVM, PhD, DACVIM, DACUN, Knowvll, TN eS Pelce Precio ™ “eres contiaved tam previous page REFERENCES 1. Barges M4, Osbome CA, Llc JP a Methods for evaluating treatment of wos, Vet Clin North Am Small Anim Pact 1990,20:45 57. 2 Osborne CA Luh Poin Deak. Medical dissolution and prevention of caine suite wos. Twenty yeas of experience. Vet Clin North Ar Small Anim rat 1999;29:75-111 Barges Osbome CA Pozn i. Recurent stele suite urocytotiasis in vee tated Cocke Spiel. Am Anim Hosp Assoe 1992;28:459-469. SBufington 1. tte olthiss in cats. 1. Am Vet Med Ass0¢ 198;198:73, dala SU, Ostome A, Leininger, eal Exaluation ofa clei tin female dogs with induced stit wlthiass. Am | Vet Res 19845:1508-1518, Lekcharoensuk G Lich , Osborne CA, eat. Assocation between patient lated fadors and sk of calium oxalate and magnesium ammonium phosphate lias n x 1Am Vet Md Assoe 2000217'520-525. Fnco OR, Besant sA Crowell WA. Characterization of magresum-nduced winry dese in the cat and comparison with eine welogcsydome. Am Vet Res 198546:391200 8. Baington A, Rogers GR, Mons 1. Het of ton site cy productin feline wine. Am J Vet Res 1990;5:2025-2080. 9. Batfigton CA, lade, Sato fens ofTarsr-Horsall gcoprotein and albuin on stuvte crystal growth in urine of cats Am et Res 199435:965971, 10. Tartan MF Feline sti url factors fecting urine pH may be more impotart than magnesium levels in fod, Veterinary Record 1987;!21:227 230. 11. Barges 1, Taner SL, Scheider C.Cormparson of trite actly product ais ad relative supesaurains in wine colected from heathy cts consuring four trite management des, Raton Purina Nurtion Symposium 1968, 12, Osbome CA Luc Kruger JM, a: Madi soln af eine suite urogtalths Am Vet Mad Assoc 192:196:1053-1068, 15. Sith BH, Stevenson AE, Markl Pl. Urinary rie superatrations of acum cxalat and sna in cats ar infuence by ct. Nu 1998:128:2768S-2768. 14 Finke MO, Lizenberge 8A. Hf of food intake on une pH in cas. Small Anim Prat 1902:35:261-256. 15 Tatein MF Finest urlthiass fasting reduced the efleciveness of a urna acter ammonium clorde) and inceased the intake of alow magnesium ot. Vetevinary Record 1967/121:285228. 16.898 KC, Menon M. Mechanism of stone formation. Url Clic North Am 1997;28:1-1, 17. Barges 1 iC Lane fF Update: Management f calcium oxalate clits in dogs and cts. et Clin North Am Small Anim Pact 2008;34:969-97, i 1. Goe Ft, Pars JH, Aplin JR The pethogeness and tetrent of Kidney stones Engl Med 1992;527:1141-1152 19 Luken 1 Osborne CA Nagode LA eta Evaluation of ne and setum metabolites in miniature schnawers with clue oxalate oli’, Am 1 et Res 19915221585-1590, 20, Ching Fetiman Ml, Hamar OVE etal The effect of chronic etary acticaton sing aremenium chide on act base and mineral metabofsm inthe adult cat Journal of Nutrition 1989;11990215, Luli, Osboene CA, Sanderson Seta. sng urchydopropubion: Lessors ftom 5 years of experience. Vet Clinic North Amer Small Anim Pract 199979:285.292. cain HM, Sasa I, Barges Hypercalcemia and cam oxalate otha cats: a report of ve case. Am Anim Hosp Assoc 1999:35267-301 ik CA Ling Gy, Frat Ce, tal Evaluation of factors assoioted with development of calcium oxalate wiiasis inci. 1 Am Vet Med ASSoe 1995;207:1429-1434 24, ThumehaiR Wich Osborne CA, tal Epzotclogic evaluation of urls in as: 5498 cases (1982-192).1 AM Wet Med ASSOC 1996:205'587 51. 25, Ki A Ling Gu Osborne CA et al ial guidlines or managing cakium oxalate welts in cats: medical they, hyation and detay therapy. Managing olin cas recent updates and practic guidelines. Topeka, KS: H's Ret Nuon In, 2005/10-9. 26, Stevenson AE, Hynds WK, Madel Elect of dietary moisture and sedium content on urine compesion and calcium oxalate elatve supersaturation in heathy rinitureschnouzers and labredor reeves. Res Vet Sel 2005,74:145-151, 27. Barges 4 Osborne CA Lich J, a. Canine vate UEhas. pathogenesis, agnosis and management Vet Cli Noth Aen Small Ain Pract 1999;29: 161-191, x 28, Osborne CA Barges IN Lulich J, eal Canin uothiass in: Hand MS, Thatcher CO, Remi RL etl, eds. Smal Amal Cinical Nuton. th ed Marceline MO: Wadsworth Publishing Co, 2000;605-658, 23, Marea SM, Pask A, Greene RY tal. Usnarycaleul assoited with portosysteric shuns in si dogs. Am Vet Med Assoc 198;178:133-187 30, Hardy RM, Klausner Urte caleul associated wih portal vascular anomalies I: Kr, ed, Curert veterinary therapy Vl Philadelphia: WB, Saunders Co 19851073. 531. Brain Pat Portcsystomic shunts - urate cau asa guide to agnosis Aust Vet Pract 1988:18:-8 '32. Johnson CA Amstong Pl, Hauptman JC. Congenital pontosjtemic shuns in dogs: 46 cass (1979-1986). Am Vet Med Asso€ 1987;1:1478 1483, ovee BBE Special thanks 19 Dr: Bartges for sharing this information with us! He is a wonderful speaker and generous educator.IEA CoM CN Lol USMC TANG 2 ORME STOTT Feline Pract 2008 Research Grant The American Association of Feline Practitioners (AAFP) will present a research award in 2008 for meaningful research in feline medicine andor surgery. The $20,000 award will be given to the researcher whose application shows the most clinical merit Past research projects and recipients of the award have been: 2007: Evidence of Effective Drug Delivery Using Transdermal Dr. Dawn M. Boothe, DVM, PhD, DACVIM, DAC 1 Delivery Ssiems in Cats P, Auburn University, AL 2006: Prostaglandin E2 Signaling in the Feline Mammary Cancer: A Potential Target for Chemotherapy Dr Sakhila Banu, Texas A&M University, College Station, TX 2005: Gene Expresion Profiling of Feline Alimentary Lymphoma Mary Lynn Higginbotham, DVM, MS, DACVIM-Oncology, Auburn University, AL Enaluation of Gstatin C as an Endogenous Marker of Glomerular Filtration Rate in Cats ‘Thomas Graves, DVM, PhD, DACVIM, University of Illinois, Urbana, IL 2003: The Awociaton of Bartonella sp. Infection with Chronic Stomatitis in Cats Kristy L. Dowers, DVM, DACVIM-Clinical Sciences, Colorado State University, Ft. Collins, CO 2002: Mitacantrone and Piroxicam Versus Piraxicam Therapy Alone for the Treatment of Feline Oral Squarmous Cell Carcinoma Carolyn Henry, DVM, University of Missouri-Columbia, Columbia, MO For more information go to wwve.aafponline.org for grant application and instructions, including the criteria for grant selection, and a time line for the grant and reporting process All appl ions and 10 copies of the proposal must be received in the AAFP office by December 15, 2007. AAFP, 203 Towne Centre Drive, Hillsborough, NJ 08844 Save the Date: AUTOS comms) a Conference ees oa Palm Springs, California Roe ed Caen)