Urolithiasis & Chronic Renal Failure in an 8 Year Old Pony Gelding

1. Urolithiasis and Chronic Renal Failure in an 8 Year Old Pony Gelding Kelly McGowan UF College of Veterinary Medicine, Class of 2014 mcgowank@ufl.edu 210 NW 33rd Ave Gainesville, Florida 32609 Mentors: Dr. Amy Stieler, DVM; Dr. Sarah Reuss, VMD, DACVIM

2. SIGNALMENT & HISTORY • 8 year old large pony gelding • Show hunter wintering in Ocala, Florida • Long term NSAID (firocoxib) use for chronic lameness

3. RECENT HISTORY • Presented to the referring veterinarian for the following: • Stranguria • Pollakiuria • Hematuria • Referred to the University of Florida Large Animal Hospital • Tentative diagnosis of a urethral tear by another referring veterinarian

4. CLINICAL FINDINGS • Bright, alert, responsive • Body Condition Score: 6/9 • Pink mucous membranes • Temperature: 99.5 • Heart Rate: 36 beats per minute • Respiratory Rate: 16 breaths per minute • Groaning noted during urination • Free catch urine cloudy and yellow with white precipitate

5. INITIAL DIAGNOSTIC PLAN • Urinalysis • CBC • Chemistry • Rectal Palpation and Ultrasound • Abdominal Ultrasound • Cystoscopy Presenting signs may be renal or post-renal in origin. The above diagnostics will help localize the problem.

6. INITIAL DIAGNOSTIC PLAN Urinalysis - 12/3

7. INITIAL DIAGNOSTIC PLAN CBC – No Significant Findings 12/3

8. INITIAL DIAGNOSTIC PLAN Serum Biochemistry Abnormalities – 12/3

9. PROBLEM LIST • Stranguria • Hematuria • Proteinuria • Crystalluria • Bacteriuria • Hypercalcemia • Hypophosphatemia • Hypermagnesemia • Hyponatremia • Azotemia

10. DIFFERENTIAL DIAGNOSES Stranguria, Hematuria, Proteinuria, Crystalluria Infection E. coli C. renale Inflammation Trauma Urolithiasis Neoplasia Renal cell carcinoma Squamous cell carcinoma Transitional Cell Carcinoma Electrolyte Derangements Chronic kidney disease Secondary to calculus formation Chronic interstitial nephritis Azotemia Renal Postrenal *Pre-renal azotemia ruled out based on USG

11. DIAGNOSTIC PLAN • Rectal Palpation • Abdominal Ultrasound • Cystoscopy • Additional Chemistry Panels • Nuclear Scintigraphy The above diagnostics will help localize the problem to the kidneys, ureters, bladder, or urethra

12. DIAGNOSTIC PLAN Rectal Palpation Evaluation of gross internal anatomy Evaluation of kidney size and shape Evaluation of dorsal aspect of bladder • Trans-Rectal Ultrasound • Left kidney small and hyperechoic • No corticomedullary distinction • Left kidney palpated small and firm • Stone palpated within the bladder • No other abnormalities noted

13. DIAGNOSTIC PLAN Trans-Abdominal Ultrasound Evaluation of bladder wall thickness and texture Evaluation of kidney size, shape, architecture Identification of abscesses, cysts, neoplastic masses, dilated ducts, cystoliths, nephroliths • Left kidney not appreciated • May indicate chronic kidney disease • Right kidney of normal size and architecture • Does not entirely rule out presence of disease • No other abnormalities noted Ultrasound image of right kidney, outlined in red

14. DIAGNOSTIC PLAN Cystoscopy Evaluation of bladder wall mucosa Evaluation of ureteral size and function Identification of cystoliths, neoplastic masses • 6cm round, firm, cystic calculus • May be cystic or nephric in origin • Dilated left ureteral opening and ureter • May be do to passage of nephro-/ureterolith • No urine seen (not visualized) exiting left ureter • Possibly due to ureteral blockage, or renal insufficiency Endoscopic image of a large calculus within the bladder

15. DIAGNOSTIC PLAN Cystoscopy Endoscopic image of the dilated left ureter, marked by the red circle. Note the lack of urine flow. Endoscopic image of the right ureter, marked by the red circle. Note the urine flow.

16. DIAGNOSTIC PLAN FOR LEFT KIDNEY • Nuclear Scintigraphy • Radiopharmaceuticals injected into the bloodstream are detected by a gamma camera • Provides an estimation of renal perfusion and glomerular filtration rate (GFR) • Absent blood flow to left kidney • Absent metabolic activity in left kidney Dorsal view showing a right kidney, and absent left kidney. Red circle indicates approximate location of left kidney.

17. DIAGNOSTIC PLAN FOR LEFT KIDNEY Serum Biochemistry Abnormalities – 12/10 Risk of biopsying the left kidney through the spleen was deemed unacceptable because the lack of blood flow had been confirmed by nuclear scintigraphy, as well as the lack of urine flowing from the left ureter.

18. DIAGNOSIS • Urinary tract infection • Urolithiasis • Chronic kidney failure of the left kidney • Cause unclear • Possibly due to calculus formation

19. TREATMENT PLAN Organisms common in UTIs Escherichia coli Staphylococcus species Corynebacterium species Klebsiella species Enterobacter species Pseudomonas aeruginosa • Commonly used antibiotics • Trimethoprim-sulfonamide • Ceftiofur • Enrofloxacin • Penicillin • Ampicillin • Chloramphenicol • Started on ceftiofur, 2.2 mg/kg IV BID during hospital stay • For treatment of the urinary tract infection • Based on culture and sensitivity • Broad spectrum activity, bactericidal • Eventually discharged with trimethoprim-sulfonamide tablets, 30 mg/kg PO BID • Easier administration for home treatment • Sulfadiazine excreted primarily unmetabolized in urine • Broad spectrum activity, bactericidal

20. TREATMENT PLAN • Perform perineal urethrostomy (PU) • An opening into the urethra through the perineum • Allows passage of urine and small calculi without blocking the penile urethra • Caudal epidural performed prior to surgery • 10mg morphine • 50mg lidocaine • 17mg xylazine • Sedated with a detomidine continuous rate infusion • 35mg total • Butorphanol administered IV as needed • 14 mg total Perineal Urethrostomy Site

21. TREATMENT PLAN • Mechanically ablate cystic calculus • Cystolith will be broken into small pieces to allow passage through PU incision using mallet, uterine biopsy forceps, and the endoscopic basket • Follow with copious lavage to flush stones out of the bladder • Performed on 3 consecutive days using endoscopy to confirm removal of all debris • Other options for stone removal include: • Ventral/paramedian celiotomy • Cystotomy • Owner elected to try PU with manual ablation Small calcium carbonate stones following manual ablation

22. TREATMENT PLAN • Cystoscopy 24 hours post-operatively • To confirm the passage of calculi, or their • continued presence • Multiple cystic calculi present, 2-3cm diameter • Right ureter patent and flowing • No urine seen exiting left ureter Endoscopic image of calculi following mechanical ablation. Note absent urine flow from left ureter, marked by red circle.

23. TREATMENT PLAN • Nephrectomy with Surgical Pathology and Culture • Left kidney is non-functional, confirmed by scintigraphy • Non-functional kidney may be a nidus for infection, resulting recurring urinary tract infections • Performed standing with through a left flank incision with a local block • Surgical Pathology Results • Chronic glomerulointerstitial fibrosis • Nonsupperative nephritis • Tubular degeneration • Necrosis and regeneration • Interstitial hemorrhage • No obvious cause, could be due to a calculus • Culture Results • No growth • Post antimicrobial treatment Image of the left kidney. Note the small size relative to the surgeon’s hand.

24. TREATMENT PLAN • Diet modification • For prevention of recurrent calculus formation • To maintain renal health • “SoyChlor” Urine Acidification Supplement • Alkaline urine predisposes to calculus formation • Supplement can be mixed with sweet feed • Provides additional acidification • 10% (low) protein formulation due to decreased renal function • Monitor urine pH regularly to titrate SoyChlor dose • Feed grass hay, such as Timothy • Hays high in Calcium, such as Alfalfa, should be avoided • High dietary Calcium can lead to calculus formation • Salt Block • Increased salt intake will encourage water intake • Promotes dilute urine • Dilutes minerals and solutes in urine

25. TREATMENT PLAN Additional Considerations • Restrict to stall rest for 1 month • Hand walking permitted • Follow with 3 weeks of turnout in small paddock before return to work • Water Consumption • Of utmost importance for kidney function • Intake should be monitored • 30 liters every 24 hours • Avoid NSAID Use • Nephrotoxic drugs could damage remaining kidney • Encourage stone formation

26. FOLLOW UP 1 Month Check-Up – Clinical Pathology • Chemistry Panel • Normal creatinine • CBC • No significant abnormalities • Urinalysis • pH 7 • Indicates the acidification supplement is working • Specific gravity 1.028 • Indicates the remaining kidney is able to concentrate urine • No blood, casts, or bacteria seen

27. FOLLOW UP 1 Month Check-Up – Imaging • Ultrasound • Targeted to right kidney • No evidence of stones within renal pelvis • No evidence of hydronephrosis Ultrasound image of right kidney, marked by blue “X”

28. FOLLOW UP 1 Month Check-Up – Imaging • Cystoscopy • No evidence of stones • Normal urine flowing from right ureter • Perineal urethrostomy site has healed well Endoscopic image of bladder, showing normal mucosa with no evidence of calculi

29. FOLLOW UP Return To Work • Three months post-op • Alec has returned to his normal program • Successfully competing in the large pony hunter ring

30. REFERENCES & FURTHER READING Van Metre, DC. Diseases of the Renal System. In: Large Animal Internal Medicine, 4th ed. Ed: Smith, BP, Mosby Elsevier, St. Louis. 2009. Pp. 925-971 Duesterdieck-Zellmer, KT. Equine Urolithiasis. Vet Clin Equine 2007;33:613-629. LeRoy, B, Woolums, A, Wass, J, Davis, E, Gold, J, Foreman, JH, Lohmann, K, Adams, J. The relationship between serum calcium concentration and outcome in horses with renal failure presented to referral hospitals. J Vet Intern Med 2011;25:1426-1430. McKenzie, EC, Valberg, SJ, Godden, SM, Pagan JD, Carlson, GP, MacLeay, JM, DeLaCorte, FD. Plasma and urine electrolyte and mineral concentrations in Thoroughbred horses with recurrent exertional rhabdomyolysis after consumption of diets varying in cation-anion balance. Am J Vet Res 2002; 63(7):1053-60 Goff, JP, Ruiz, R, Horst RL. Relative acidifying activity of anionic salts commonly used to prevent milk fever. J Dairy Sci 2004;87:1245-1255.

31. ACKNOWLEDGMENTS Thank you to all of the veterinarians at UF that were a part of Alec’s care: Internal Medicine: Dr. Sarah Reuss, VMD, DACVM;Dr. Robert MacKay, BVSc, PhD, DACVIM; Dr. Amy Stieler, DVM; Dr. Louise Husted, DVM, PhD Surgery: Dr. David Freeman, MVB, MRCVS, PhD, DACVS; Dr. Sarah Graham, DVM, DACVS; Dr. David Dymock, DVM. Photographs courtesy of Dr. Sarah Reuss and Dr. Amy Stieler, to whom I owe my thanks for their time and seemingly endless patience.