Dietary management of cystic calculi in a horse

............?... .......

Refereed

DIETARYMANAGEMENTOF CYSTIC CALCULIIN A HORSE R. L. Remillard, PhD, DVM, ACVN Diplomate; 1 P. D. Modransky, DVM, MS; 2 E H. Welker, DVM, MS; a and C. D. Thatcher, DVM, PhD2.ACVN Diplomate

SUMMARY

Principles in the dietary management of urolithiasis which have been successful in small animal cases were implemented in an equine case. This article describes the dietary management of a horse which repeatedly formed calcium carbonate cystic calculi. Treatment management included progressively decreasing the ration calcium content to reduce the intake of calcium. In addition, urinary tract infections were controlled and urinary acidification was used to inhibit calcium carbonate formation. Successful management was achieved by feeding a 0.2% calcium oat hay ration and administering 175 mg ammonium sulfate per kg body weight orally twice daily for 7 months which produced a urine pH of 5.0. There was no evidence of metabolic acid/base imbalances nor skeletal depletion of calcium. The horse has been free of cystic calculi for an additional 30 months while adequately maintained on a nutritionally balanced oat hay Authors'address: 1Clinical nutrition residency funded by Hill's Pet Product, Inc., Topeka, KS 66606. Present address for reprints: The Johns Hopkins Hospital, 600 N. Wolfe St., Department of Surgery- Pediatric Division, CMSC 7-116, Baltimore, MD 21205; 2Large Animal Clinical Sciences Department, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061; and 3"l'heOhio State University, Marysville Large Animal Service, Marysville, OH 43040. Acknowledgments: Funded bythe U. S. Trotting Association, 750 Michigan Ave., Columbus, Ohio 43215 and Large Animal Clinical Sciences Department, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Va 24061.The authors wish to thank Dr. Lon D. Lewis for his insightful commentary and valuable suggestions made throughout the management of this case.

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ration. Reducing dietary calcium intake and urine pH are possible management procedures in the horse with recurrent cystic calculi.

INTRODUCTION

A review of the veterinary literature reports some 99 cases of cystic calculi in the horse and each involved surgical removal of the uroliths. It is not completely understood why stones form in the bladder rather than being flushed out with urination. The incidence of cystic calculi is reported to be higher in stallions (22 cases) and geldings (55 cases) than in mares (22 cases), presumably because the urethra in males is much narrower than in females. 1 The calculi are most often composed of calcium carbonate with traces of magnesium, ammonium and phosphate. 2 Treatment has been surgical removal of the calculi via cystotomy, or possibly a urethrostomy, followed by antibiotic therapy. Recurrence rate is thought to be low; however, post-surgical dietary management may be instituted as a preventive measure. The recommendation to lower calculi minerals in the diet is made based upon the strong research evidence in man and other animals that supersaturation of the urine with calculi forming constituents is required in calculi formation.3 Secondly, there is evidence that decreasing the dietary intake of the calculi minerals will decrease the urine concentration of those minerals, 4 and therefore, calculi formation. These dietary recommendations are routinely made in appropriate

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small animal cases; therefore, the same recommendations may be made to horse owners as a preventive measure. Dietary management of uroliths in the dog and cat has been successful, both in the dissolution and prevention of urinary calculi. The calcium carbonate uroliths most often found in the horse are not common in the dog or cat. However, stones which are composed of magnesium, ammonium phosphate, calcium and urate have been successfully managed through appropriate dietary manipulations. Dietary management may save the owner the expense of additional surgeries or the decision of euthanasia and would also improve the prognosis following the first surgical procedure. The case presented herein is a classic representation of equine urolithiasis, except the recurrence rate was high in that several stones were removed surgically on four separate occasions. The horse produced these cystic calculi within a 15-month period until dietary management was instituted. To the best of the authors' knowledge, this is the first published case demonstrating the usefulness of dietary manipulations in the management of equine urolithiasis.

METHODS AND MATERIALS History

A5 year old Thoroughbred gelding (450 kg) was presented to the Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM) Teaching Hospital with a three month history of dysuria, pollakiuria and hematuria. The horse had only been purchased one month prior to the onset of clinical signs and historical information beyond the last four months was not available. A large spiculated cystic calculus was found on rectal palpation and confLrmed using ultrasonography and cystoscopy of the bladder. A single large yellow calculus was surgically removed through a ventral abdominal incision and cystotomy and qualitatively analyzed to be predominately calcium carbonate. A bladder mucosal swab obtained intra-operatively isolated a Proteus species but no bacterial growth was obtained from the urine. The horse was released to the owners with antibiotic therapy (Tribrissen 15 mg/kg PO BID) and the owner was advised to sample and analyze the feedstuffs fed to the horse for a ration evaluation. The owner elected not to evaluate the ration at that time. Six months following the first surgery, there horse was presented a second time with hematuria and dysuria. Two cystic calculi were found and the owners elected to donate the horse to the VMRCVM rather than pursue a second surgery. A urine sample, obtained via catheterization, again produced no growth on culture. These calculi were removed by a second ventral abdominal incision and cystotomy. The previous surgical site was closely inspected and was not considered involved in the recurrence of the calculi. Bladder wall biopsies, obtained intra-operatively,had histological changes confLouis C. Herring & Co., Analytical and consulting Chemists, 1111 S. Orange Ave., Orlando FL 32806.

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Table 1. Nutrient profile of r a t i o n s as c o m p a r e d with N R C minimums.

Nutrient

NRC6 1

Dry matter (%)

--

89.7

Rations" 2 82.1

3 88.3

...................... DM Basis ................... Digestible Energy (meal/kg)

2.00

2.72

2.42

2.73

Protein (%)

8.00

15.78

12.70

7.40

Calcium (%)

0.24

0.68

0.39

0.20

Phosphorus (%)

0.17

0.43

0.38

0.13

Magnesium (%)

0.09

0.36

0.22

0.16

Potassium (%)

0.30

2.69

2.50

1.15

kAII rations were offered ad libitum; the horse consumed 6-8 kg/d. Ration 1 - fescue-clover pasture, alfalfa hay and grain mix,; Ration 2 - grass hay; Ration 3 - oat hay. Water and trace mineral salt block were available at all times.

sistent with chronic inflammation but no neoplastic changes. Using quantitative crystallographic analysis,f the calculi were determined to contain calcium carbonate (90%) and protein (10%) with no microscopically distinct nucleus. The horse had been maintained on a rescue and red clover pasture the previous six months with an oat-soybean meal-barleymolasses grain mix (4 kg/d). Alfalfa hay (10 kg/d) was fed during the winter months when pasture was inadequate. The winter feeds were sampled by the owner, analyze# and ration 1 was reconstructedh (Table 1). Dietary management of the cystic calculi was attempted because the horse appeared to be normal in all other respects.

Dietary management The horse was individually housed in a dry lot and received a physical examination monthly at the VMRCVM which included rectal palpation of the bladder, urine analysis and serum profile. A grass hay ration (#2) was offered to the horse ad libitum, with free access to water and a trace mineralized salt (TMS) block. Ration 2 (Table 1) was designed to reduce the intake of protein and calcium (Ca) as compared with ration 1, as they were the main components of the calculi. The horse consumed, on average, 6 to 8 kg of ration 2 per day, and maintained appropriate body weight and condition. Two 24-hour total voided urine collection trials with serum electrolyte measurements were made after the horse had been fed the grass hay ration for 8 weeks. Renal clearance and fractional excretion of creatinine were similar to reported normal values; however, clearance and fractional excretion estimates for calcium were greater than 2 standard deviations (SD) from reported normal values (Table 2).s Serum parathormone (PTH) concentration (17 pg/ml) measured while the OVirginia Tech Forage Test Laboratory, Blacksburg, VA 24061. hMixlt 2+. Agricultural Software Consultants, KJngsville, TX 78363, aDr. Larry Nagode, Department of Veterinary Pathology, Ohio State University, Columbus, Ohio 43210.

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Table 2. Indices of calcium metabolism feeding grass hay (Ration 2) vs oat hay (Ration 3).'

Rations Parameters

Normal values

2

Dietary calcium (%DM) Serum calcium (mg/dl)

0.246 10.7-13.4 m

0.39 11.3

0.20 11.8

Serum PTH (pg/ml)~ Osmolality (mosm/kg)n

20-30

17

54

1085 278 _.o

1578 267 3220

1350 285 3811

1.877±0.456 0.026±0.0267

1.740 0.081

1.357 0.054

1.49±1.58

4.77

3.98

urine plasma Urine volume (ml/d)

3

Mean ± 1 SD" Clearance: creatinine (ml/min/kg) calcium (ml/min/kg) Fractional excretion: calcium (%)

~/alues for each diet are the average of two consecutive 24-hr total urine collections,exceptfor serum PTH. "Virginia-Maryland Regional College of Veterinary Medicine Clinical pathologyLaboratory. nNormalvalues obtainedfrom reference#5. °Dependentupon hydrationstatus.

horse consumed ration 2 was considered low-normal; inormal equine values range between 20 and 30 pg/ml in this laboratory. Serum electrolytes (calcium, phosphorus, sodium, potassium, chloride and magnesium) concentrations were always within normal limits. Clearance and fractional excretion estimates for phosphorus, sodium, potassium, chloride and magnesium (data not shown) were also well within normal range. A urine subsample was cultured and grew Streptococcusfaecalis, which was considered a contaminant. Two days following the urinary collection trial, the kidneys were examined ultrasonographically and were found not to contain uroliths. Percutaneous biopsies of the kidneys were also considered histologically normal. After three months of feeding ration 2 and the second surgery, several small cystic calculi were found during a regular monthly examination. A free-catch urine sample isolated Streptococcus faecalis, a contaminant. The calculi fragments were removed through a penile urethrostomy and analyzed by crystallography to be calcium carbonate (85%), protein (10%) and magnesium ammonium phosphate hexahydrate (5%). The ration was changed to an oat hay (#3) and offered ad libitum with free access to the same water and TMS block. Ration 3 (Table 1) was designed to further reduce the intake of protein, calcium, phosphorus and magnesium. The horse consumed, on average, 6 to 8 kg of ration 3 per day, and maintained a good body weight and condition. After six months of feeding ration 3, a fourth cystic calculus was found. A second penile urethrostomy site was created, but the calculus was accidently crushed during rectal palpation and Volume 12, Number 6, 1992

the fragments were apparently excreted via the urethrostomy site. These fragmentswere not recovered and, therefore, could not be analyzed. At this time, serum parathormone (PTH) concentration was 54 pg/mli while the horse was consuming ration 3. The elevated PTH was expected because the horse was receiving a borderline calcium deficient diet (Table 1); however, serum calcium levels remained within the normal range of 10.7 to 13.4 mg/dl. Radiographs of the head were completed to monitor the density of the flat bones and were considered of normal density with no lytic changes evident. Decreasing mineral and protein intake alone did not completely prevent the recurrence of the cystic calculi. Further reductions of calcium, phosphorus, magnesium or protein intake were not possible using locally available feedstuffs commonly fed to horses. A purified diet was not considered reasonable because the simplest form of dietary management for practical use was desired. Therefore, lowering the urine pH to disfavor crystallization was attempted. Urine pH in this horse had consistently been normal (8.0 to 8.5). Calcium carbonate crystals form in alkaline pH and should dissolve in an acidic pH, although the exact pH for dissolution is not known. A urinary pH of 5.0 was chosen because calcium carbonate crystals were not seen in urine sediment at a pH less than 6.0. Urinary acidification was instituted in conjunction with the oat hay ration for management of these calculi. Ammonium chloride (NH4CI) and ammonium sulfate ((NH4)2 SO4) are urinary acidifiers fed to ruminants in the control of urolithiasis; however, successful feeding of these acidifiers to the horse has not been reported to our knowledge. The horse was initially administered ammonium chloride (100 mg/kg PO BID) for four days. The urine pH values of samples obtained via catheterization were measured once daily at the midpoint between the AM and PM treatments.A pH of 6.5 was achieved within 24 hours but remained at that pH the remaining three days. The horse did not consume the ammonium chloride voluntarily and the acidifier had to be administered orally with a dose syringe. Ammonium sulfate, i which is considered more palatable than the chloride form, was administered at 100 mg/kg PO BID and increased until a urine pH less than 6.0 was achieved. Ammonium sulfate administered at 175 mg/kg PO BID produced a urine pH of 5.0 within 12 hours of dosing. The oat hay ration with ammonium sulfate treatment was continued for seven months with monthly physical examinations. Urine pH remained at approximately 5.0 when the voided sample was immediately tested. Urine pH increased as the sample was allowed to set at room (23"C) or refrigerator temperatures (4"C). There was no evidence of cystic calculi during this seven month period of feeding the oat hay ration and ammonium sulfate. A second trial consisting of two 24-hr total urine and fecal collections was performed after the horse had been consuming the oat hay ration plus ammonium sulfate for five months. Renal clearance and fractional excretion for creatiJAmmoniumsulfate, (A 4915) Sigma Chemical Company, St. Louis, MO 63178-9916.

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nine were again within the normal range of values (Table 2). Renal clearance of calcium was also within the normal range; however, fractional excretion of calcium was again greater than the expected high normal value (mean + 2 SD). Serum electrolytes (calcium, phosphorus, sodium, potassium, chloride and magnesium) concentrations remained within normal limits. Clearance and fractional excretion estimates for phosphorus, sodium, potassium, chloride and magnesium (data not shown) were again well within normal range. Total calcium consumed and fecal excretion were measured to estimate calcium balance. The averaged calcium intake (feed, water) was 13.0 g/d with an averaged calcium output (feces, urine) of 14.0 g/d. The 2-day averaged balance was -1.0 g Ca/ d indicating the intake of calcium from the oat hay diet was less than the animal excreted. The calcium concentration of the oat hay diet was slightly less than the National Research Council (NRC) (Table 1) minimum recommendations and the horse did consume a low-normal quantity of dry matter (6.0 kg/d) during the collection trial. The negative Ca balance is probably accurate but may not correctly reflect the Ca balance of the horse when greater quantities of the oat hay ration were consumed. The ammonium sulfate treatment was discontinued after seven months but the horse was continued indefinitely on the oat hay ration with monthly physical examinations. Since January of 1990, the horse has maintained a good body weight and excellent condition while consuming only the oat hay ration with no evidence of cystic calculi or calcium deficiency.

DISCUSSION

Four principles of dietary management of urolithiasis which have been successful in canine and feline cases were implemented in the present case. The first is that urinary tract infections, which may serve as a nidus of formation, must be controlled. This was accomplished through the appropriate use of antibiotics and continued monitoring. The second principle is to quantitatively determine urolith composition and reduce those constituents in the diet. The cystic calculi were primarily composed of calcium, and diets were formulated to decrease the intake of calcium. Horses and ponies excrete a larger proportion of intestinally absorbed calcium via the kidneys, as compared with ruminants, and as the quantity of absorbed calcium increases, a greater proportion of that Ca is excreted.r Alinear equation with a relatively high correlation coefficient (r2 = 0.893) was determined between Ca intake (X) and urinary Ca excretion (Y) using Schryver et al. (1974) Table 2 young horse and pony data: Y = 0.2222 x - 2.617. The regression equation predicts a horse would excrete 10.7 mg Ca/kg BW/d when consuming 60 mg Ca/kg BW/d.

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In the present case, as determined from the first urine collection trial data, the horse consumed 60.7 mg Ca/kg BW/d when fed the grass hay ration 2 and excreted 13.8 mg Ca/kg BW/d via the urine. There is apparently a strong relationship between dietary calcium intake and renal excretion. It seems reasonable, therefore, that decreasing Ca intake should be an integral part of calcium carbonate urolith treatment in horses. Dietary phosphorus has been shown to influence calcium absorption and renal excretion in ponies, e Ponies fed high phosphorus diets (1.19%) had significantly higher fecal calcium concentrations and lower quantities of calcium excreted by the kidneys with lower plasma calcium levels. The dietary calcium to phosphorus ratio was inverse to achieve these results and was not considered desirable in the long-term management of the present case. The water in Virginia is considered to have higher than the national average in calcium concentration. Mineral analysis of the water source indicated concentrations of 11.5 mcg/ml calcium, 0.2 mcg/ml phosphorus and 9.1 mcg/ml magnesium. Calcium intake from water alone was 1 mg Ca/kg BW/d and was not considered a major factor to be controlled compared with a feed intake of 60 to 70 mg Ca/kg BW/d. Thirdly, urine pH may be altered to prevent crystallization of the minerals. Equine urine pH is normally alkaline which favors calcium carbonate crystallization. An acidic urine pH (5.0) was consistently achieved in the present case using ammonium sulfate, although ammonium chloride may work as well. No calcium carbonate crystals were observed in the urine sediment at a pH less than 6.0. Neither acidifier was voluntarily consumed by the home, even when combined in a oat grain-molasses mixture. An acceptable dosage schedule was determined to be oral treatments five days a week with no treatments on weekends. An every other day treatment schedule, however, may also be successful. The fourth principle in the management of uroliths is to increase urine production to increase volume and low, in attempts to decrease the time period in which crystallization may occur in the bladder. In pet foods this is accomplished by increasing the sodium content of the diet. Increasing the sodium content of the diets of people and rats has increased the renal excretion of calcium.9'1° However, increased sodium intake has not been shown to effect renal excretion of calcium in the home, but does enhance calcium and phosphorus absorption and retention.11 In the present case, sodium in the diet was neither restricted or increased. The horse was allowed flee access to the TMS block and consumed the block at rates considered normal compared with other homes in the facilities, although the intake was not quantitated. In summary, the kidneys were considered normal based upon ultrasonic and histologic examinations. Clearance and fractional excretion of creatinine and other electrolytes were determined to be within normal ranges, and serum PTH was also determined to be normal or appropriate on two separate

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occasions. The fractional excretion of calcium at 4% was a high normal value determined on both the grass hay and oat hay rations, and may be related to the etiology of calculi formation. Therefore, decreasing the dietary constituents of the calculi, as well as controlling urinary infections and disfavoring calculi formation with an altered urine pH may all be implemented in equine cases to inhibit cystic calcium carbonate calculi formation with success.

REFERENCES

1. DeBowes RM, Nyrop KA, Bowlton CH: Cystic calculi in the horse. Comp Cont ted 6(5):$268-272,1984. 2. Osborne CA, Shanna JJ, Unger LK, et al: Analyzing the mineral composition of uroliths from dogs, cats, horses, cattle, sheep, goats and pigs. Vet Med 84(8):750-764,1989. 3. Osborne CA, Polzin DJ, Abdullahi SU, et al: Struvite urolithiasis in animals and man: Formation, detection and dissolution. Ad in Vet Sci and Comp Med 29:1-101,1985.

4. Lewis LD, Chow FHC, Tato GF, et al: Effect of various dietary mineral concentrations on the occurrence of feline uroiithiasis. J Amer Vet Med Assoc 172:559-563,1978. 5. MorrisDD, Divers TJ, Whitlock RH: Renal clearance and fractional excretion of electrolytes over a 24-hour period in horses. Am J Vet Res 45(11):2431-2435,1984. 6. National Research Council: Nutrient requirements of horses. National Academy Press:Washington, DC, 1989. 7. Schryver HF, Hintz HF, Lowe JE: Calcium and phosphorus in the nutrition of the horse. Cornel/Vet 64:493-515,1974. 8. Meacham VB: A review of calcium, phosphorus and magnesium metabolism in the horse. Equine Vet Sci 4(5):210214,1984. 9, Kleeman CR, Bohannan J, Bernstein D, et al: Effect of variations in sodium intake on calcium excretion in normal humans. Proceedings Soc Exptl Biol Med 115:29-32,1964. 10. GouldingA, Campbell DR: Effect of oral loads of sodium chloride on bone composition in growing rats consuming ample dietary calcium. Min Elect Metab 10:58-62,1984. 11. Schryver HF, Parker MT, Daniluk PD, et al: Salt consumption and the effect of salt on mineral metabolism in horses. Cornel/ Vet 77:122-131,1987.

EXPLAINING LAMINITIS AND ITS PREVENTION By Robert A. Eustace, BVSc, E.O. Cert. E.P. MRCVS The Laminitis Clinic, University of Bristol A B O O K FOR Y O U R C L I E N T S This book is the only one presently available which passes on to the 'ordinary' horse owner, with perhaps little scientific knowledge and who has been brought up along traditional lines as far as horse management is concerned, the state-of-the-art knowledge which can now save the lives of affected animals and probably prevent them developing laminitis in the first place. We now know it is quite wrong to force-walk laminitic animals, to inject them with corticosteroids and to put them on 'starvation' diets, although these practices are still often regarded as standard remedies. Laminitic animals need very specific management, veterinary treatment and nutrition without 'starvation'. This book explains fully, in easily understood terms, our present knowledge of the disease and how to prevent it, and, therefore, how to save your horse or pony's life. It is written by a world authority on the disease who has saved the lives of many animals who would otherwise have been put down, in many cases restoring the animals concerned to working lives. You will learn how to recognize laminitis quickly with simple daily checks, you will come to understand the vital importance of prompt treatment of the correct kind and how essential correct management and nutrition (detailed in this book) are to both prevention of and recovery from laminitis. You will no longer have to cope with a chronically laminitic animal because the fact is that if your horse or pony has had laminitis once there is almost certainly no need for him to get it again. If you follow the advice in this book, its recurrence is not inevitable. Probably most important of all, you will learn how to recognize it if it does occur and how to prevent it in the first place. You may be surprised at some of the advice you read as it is contrary to what has been, and still is, widely believed and taught about laminitis. But you can rely completely on the advice in these pages as being the most up-to-date and reliable so far available. If everyone follows this advice laminitis will become a rare disease. (80 pages-soft cover.) $15.95 Order from The Journal of Equine Veterinary Science PO Box 1209, Wildomar, CA 92595

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