Case Report Unilateral Nephrectomy in Two Aged Horses N

300 EQUINE VETERINARY EDUCATION / AE / July 2007

Case Report Unilateral nephrectomy in two aged horses N. FERGUSON*, L. COUËTIL, J. HAWKINS, C. ERNST†, J. SOJKA AND W. VAN ALSTINE‡ Veterinary Teaching Hospital, Purdue University, 625 Harrison Street, West Lafayette, Indiana 47907; †Benker Veterinary Clinic, 707 Edith Avenue, Noblesville, Indiana 46060; and ‡Animal Disease Diagnosic Laboratory, Purdue University, 406 S University, West Lafayette, Indiana 47907, USA. Keywords: horse; kidneys; renal physiology; urinary tract; pathology; clinical chemistry; renal function

Introduction

There is a paucity of information in the veterinary literature assessing renal function in horses that undergo unilateral nephrectomy, in particular determining which horses are ideal candidates with regards to evaluating the function of the remnant kidney. The cases reported here are aged horses with disease localised to one kidney due to renal tumour (Case 1) and chronic pyelonephritis (Case 2). This article describes the first case of successful nephrectomy for treatment of a renal tumour without metastatic spread in a 20-year-old Thoroughbred gelding. The type of renal tumour, a papillary adenoma, is the first case described ante mortem in the equine veterinary literature to our knowledge. In addition, this is the first paper documenting long-term evaluation of renal function after Fig 1: Case 1 cystoscopy: fresh blood observed throughout the urine stream from the right ureter. unilateral nephrectomy through serial serum biochemistry panels, haematology and urinalyses. To our knowledge, despite the occurrence of nephrectomies [rr] 12–20 mg/l) and 210–270 mg/l (rr 100–250 mg/l), in the small animal field, in particular feline medicine, no paper respectively, and urine specific gravity ranged from has addressed the immediate post operative period, nor 1.020–1.033 (rr 1.020–1.050). Palpation per rectum was assessed renal function at timely intervals post nephrectomy. within normal limits. Transabdominal renal ultrasonography performed by the referring veterinarian was nondiagnostic due Case 1 to poor image quality. Cystoscopy revealed blood-tinged urine. The horse had received phenylbutazone (1 g per os, q. 24 h) for History osteoarthritis for 2 months, discontinued 2 weeks prior to referral. A 10 day course of oral trimethoprim-sulphadiazine A 20-year-old 512 kg Thoroughbred gelding presented with a (30 mg/kg bwt b.i.d.) did not resolve the haematuria. 3 week history of gross haematuria. Serial haematology, serum biochemistry and urinalyses performed prior to referral revealed Clinical findings proteinuria and marked haematuria, as expected with gross haematuria. The serum creatinine and blood urea nitrogen At admission the horse was bright, alert, and responsive. (BUN) concentrations ranged from 13–14 mg/l (reference range Physical examination findings, including rectal palpation, were normal. Initial laboratory testing revealed mild anaemia (PCV = 33.5%; rr 35–50%), with a red blood cell (RBC) count of *Author to whom correspondence should be addressed. Present 6.82 x 1012/l (rr 6–12 x 1012/l). The horse was sedated with addresses: *University of Georgia, College of Veterinary Medicine, xylazine (0.5 mg/kg bwt i.v.) for urethroscopy and cystoscopy. Department of Infectious Diseases, Athens, Georgia, 30602; and †Janssen Veterinary Clinic, 2420 West 236th Street, Sheridan, Indiana Mild urethritis was attributed to mucosal irritation secondary to 46069, USA. frequent catheterisation and cystoscopy prior to referral. EQUINE VETERINARY EDUCATION / AE / July 2007 301

inflammatories (phenylbutazone 4.4 mg/kg bwt i.v.) were administered. Prior to sedation, visualisation of the right kidney was attempted once again via transabdominal ultrasound; gas interference precluded visualisation. The horse was restrained in standing stocks and epidural administration of 60 mg of morphine sulphate performed. The horse was sedated with detomidine hydrochloride (0.02 mg/kg bwt i.v.) and butorphanol tartrate (0.02 mg/kg bwt i.v.). The surgical approach to the right paralumbar fossa was performed as previously described (Mariën 2002). Ultrasonographic examination of the right kidney was performed in a sterile manner with a 5.0 MHz probe. A 2.5 x 2.5 cm well-circumscribed, hyperechoic mass was present in the caudal pole (Fig 2). Although an insensitive means to rule out metastases, palpation of the abdominal viscera and laparoscopic examination of the structures on the right side Fig 2: Case 1: Intra-abdominal ultrasonography of the renal revealed no abnormalities. mass at the caudal pole of the right kidney. The ultrasound probe is placed directly on the mass; normal kidney is not Based on the gross absence of metastatic disease and visualised in this field. normal appearance of the left kidney, a right uninephrectomy was performed using a hand-assisted laparoscopic technique (Mariën 2002). Despite the relatively small size of the mass Grossly normal urine flowed from the left ureter. Fresh blood and presumption that the right kidney was still functional, was observed throughout the urine stream from the right nephrectomy was needed in order to resolve the haematuria. ureter (Fig 1). Transabdominal ultrasonography of the left The mass was well demarcated from the surrounding renal kidney appeared grossly normal. The right kidney was not parenchyma (Fig 3). On cut section, the mass was granular in entirely visualised due to gas interference, and visualisation appearance and lighter than the surface of the renal cortex. via ultrasonography per rectum was unsuccessful. The mass yielded no bacterial growth. Histopathology Abdominocentesis revealed a modified transudate with normal cell morphology. The differential diagnoses for haematuria were renal neoplasia, idiopathic renal haemorrhage, nephrolithiasis and acquired renal vascular abnormalities.

Treatment

Intra-abdominal renal ultrasound via a right flank laparotomy was recommended, as a nephrectromy was anticipated in order to resolve the haematuria. This approach to diagnosing the cause of haematuria is unusual, as laparoscopic evaluation of the kidney is a less invasive approach than right flank laparotomy. However, the decision was made upon discussion with the owner to approach this case in the manner described for several reasons. As mentioned before, the right flank incision was made in anticipation of the need to perform a nephrectomy pending ultrasonographic evaluation of the right kidney. The right kidney was evaluated first in order to determine if a prognosis could be established based on ultrasonographic appearance. Although ultrasonography does not differentiate whether a mass is benign or malignant, its use lies in determining the extent of the disease process. Palpation of the internal abdominal organs was also necessary prior to nephrectomy in order to evaluate for the presence of gross metastases. Nephrectomy would not have been pursued if the prognosis for successful and long-term outcome was deemed poor. The horse was held off feed for 56 h to reduce the volume of ingesta in the gastrointestinal tract. Preoperative antibiotics (gentamicin 6.6 mg/kg bwt i.v. q. Fig 3: Case 1: Papillary adenoma at the caudal pole of the right 24 h; ceftiofur sodium 2.2 mg/kg bwt i.v. q. 12 h) and anti- kidney. 302 EQUINE VETERINARY EDUCATION / AE / July 2007

35 1.035 30 1.03 25 1.025 20 1.02 15 1.015 10 1.01

5 Urine specific gravity Serum creatinine (mg/l) Serum creatinine 1.005 Reference range: 12–20 mg/l Reference

0 range: 1.020–1.050 Reference 1 -21 -17 -3 16 17 26 32 39 130 180 540 -21 -17 -3 16 17 26 32 39 130 540 Day Day

Fig 4: Case 1: Serum creatinine concentrations (mg/l). Fig 5: Case 1: Urine specific gravity. Nephrectomy was Nephrectomy was performed at Day 0. performed at Day 0.

revealed an encapsulated papillary adenoma, composed of tubular disease. Urine GGT:Cr is used to assess inflammation papillary projections of a thin stalk covered with cuboidal to and necrosis of renal tubular cells and is not a laboratory low columnar cells containing ample eosinophilic cytoplasm parameter used to assess renal function. RBC count and and round nuclei with few mitoses. The kidney peripheral to haematocrit were mildly decreased up to Day 26, with a RBC the tumour was microscopically unremarkable. count of 6.4 x 1012/l and PCV of 30%; these normalised by Butorphanol (one dose of 50 mg i.m.) and lidocaine Day 130 post operatively (PCV: 44%, RBC count: 9.3 x 1012/l). (loading dose of 1.3 mg/kg bwt, followed by a continuous An 18 month follow-up CBC revealed a mildly decreased RBC infusion rate of 0.05 mg/kg bwt/min over 24 h) were count and PCV, respectively 6.4 x 1012/l and 31%. administered post operatively for analgesia. Phenylbutazone was replaced with flunixin meglumine (1.1 mg/kg bwt i.v. q. Outcome 12 h) as it is less nephrotoxic (MacAllister et al. 1993). The horse remained intermittently painful for a period of 18 h. No During hospitalisation, a weight loss of 23 kg was observed. other physical examination abnormalities were evident and No further weight loss was noted at home. The skin incision voided urine was grossly normal. The anti-inflammatory healed without complications. The horse regained a normal medications and i.v. antibiotics were continued for 3 days, appetite after discharge, and remained on a diet of grass hay and then replaced by trimethoprim-sulphamethoxazole one and oats with corn oil. No abnormalities were noted by the week after admission (30 mg/kg per os q. 12 h for 10 days). owner during an 18 month follow-up period. Four days post operatively, the horse was discharged without complications. Starting 16 days post operatively, follow-up Case 2 serum biochemistries, complete blood counts and urinalyses were performed. History The serum creatinine concentration was double the hospital baseline value on Day 16 (30 mg/l), started to decline A 23-year-old 391 kg Arabian mare presented with a 2 month on Day 26 (27 mg/l), normalised by Day 39, and was mildly history of anorexia, depression and weight loss. The anorexia elevated at Day 130 (22 mg/l) (Fig 4). At an 18 month recheck, resolved after a 2 week course of oral trimethoprim- the serum creatinine concentration remained within reference sulphadiazine, at which time the mare started regaining range (18 mg/l). The urine specific gravity was isosthenuric (SG weight. One month prior to presentation, thick, cloudy urine = 1.015) 16 days post uninephrectomy, and increased slightly nonresponsive to oral sulphonamides was noted. Polyuria had over time; it remained isosthenuric up to 32 days post been observed according to the owner for an unknown period operatively and normalised by Day 130 (SG = 1.032) (Fig 5). At of time, but resolved prior to presentation. 18 months, the urine specific gravity was 1.020. Although water intake was not measured during this time, observations Clinical findings both at the hospital and at home did not reveal polydypsia. At Days 17 and 26 post nephrectomy, the fractional excretion of At admission, the horse was bright, alert, and responsive. sodium (0.7 and 0.55%, respectively; rr<1%) was within the Physical examination findings were normal. Initial laboratory reference ranges. The urinary GGT to creatinine ratio at Days testing revealed a BUN of 260 mg/l (rr 80–230 mg/l) and 17 and 26 were 27 iu/mg and 20.3 iu/mg (rr<25 iu/mg). Higher sorbitol dehydrogenase (SDH) activity of 10 iu/l (rr 0.0–6.7 urinary GGT to creatinine ratio has been reported in normal iu/l). Urine obtained via catheterisation revealed moderate horses (mean ± s.d. 22.8 ± 13.7 iu/mg) (Rossier et al. 1995). proteinuria on a reagent strip (rr 0–trace), pyuria (100+ Fractional Na excretion and urinary GGT:Cr are indicators of leucocytes/high power field [hpf]; rr 0–5 leucocytes/hpf), and renal tubular integrity and sensitive markers of active renal rare bacteria. On palpation per rectum, the caudal aspect of EQUINE VETERINARY EDUCATION / AE / July 2007 303

the left kidney was enlarged and soft. Abdominocentesis Discussion revealed normal peritoneal fluid. Transabdominal renal ultrasonography revealed a large sonolucent area in the left This paper illustrates the successful treatment of unilateral paralumbar fossa, without identifiable renal tissue. The right renal disease via nephrectomy in 2 aged horses and reviews kidney appeared normal. The differential diagnoses included diagnostic methods for assessing pre- and post operative renal hydronephrosis or pyelonephritis of the left kidney. function in equine candidates for unilateral nephrectomy. To Cystoscopy revealed purulent material exuding from the our knowledge, Case 1 is unique because it describes the first left ureteral orifice and clear urine from the right ureteral case of successful nephrectomy for treatment of primary renal orifice. Thirty ml of 5% azosulphonamide, a renally excreted neoplasia in a horse. This case presented unique diagnostic injectable sulphonamide with red dye, were administered i.v. in challenges because a definitive diagnosis of renal neoplasia order to assess the ability of the left kidney to produce urine. could not be confirmed prior to the right flank exploratory Red-tinged urine was observed from the right ureteral orifice, celiotomy. This allowed us to determine the cause of renal with no change from the left ureteral orifice after administering haemorrhage as a mass involving the caudal pole of the azosulphonamide. Pyelonephritis was diagnosed, and kidney, as well as to rule out metastatic spread. The cause of confirmed on urine culture, with growth of Streptococcus haematuria was thought to occur secondary to invasion or zooepidemicus and Streptococcus equi. Quantitation was not disruption of renal vasculature by this mass. Internal performed in this case, as the accompanying high leucocyte abdominal ultrasonography was necessary in this case in count (too numerous to count/hpf) and the presence of confirming the diagnosis of right renal mass, as multiple bacteria on urine cytology, as well as the presence of purulent attempts at transabdominal ultrasonography were material exuding from the left ureteral orifice, were considered unsuccessful. The right kidney is usually imaged more easily a strong indication of a septic process. Quantification of urinary than the left kidney due to its anatomic location; however, bacteria as colony forming units (CFU)/ml is recommended as a several attempts at different time intervals to visualise the means of documenting urinary tract infections, with greater entire right kidney, in particular the caudal pole, were than 104 CFU/ml suggestive of an infectious process. The left unsuccessful. In Case 1, the decision had been made to kidney appeared nonfunctional due to the absence of renally remove the right kidney pending the gross absence of excreted azosulphonamide. Due to the normal serum metastatic disease. For the sole purpose of diagnosing a creatinine concentration (16 mg/l) and the ability to disease process in the right kidney without an anticipated concentrate urine (SG = 1.030), the right kidney was felt to be nephrectomy, attempts at visualising the right kidney minimally involved. transabdominally at multiple time points is recommended. Most reported cases of horses with primary renal neoplasia Treatment have involved metastatic disease which precluded unilateral nephrectomy (Haschek 1981; van Amstel et al. 1984; Brown Removal of the left kidney via a left flank incision under general and Holt 1985; Owen et al. 1986; Servantie et al. 1986; van anaesthesia was performed (Juzwiak 1998). Preoperative Mol and Fransen 1986; Rhind et al. 1999; Rumbaugh et al. antibiotics (sodium ampicillin 12 mg/kg bwt i.v. q. 8 h) were 2003). Because the mass was limited to the caudal pole of the continued for 48 h post operatively and replaced with oral kidney, unilateral nephrectomy was the best chance for trimethoprim-sulphadiazine (16 mg/kg bwt q. 12 h) for resolution of the renal haemorrhage. Primary renal papillary 10 days. Phenylbutazone (2 g i.v., 1 dose) was administered adenomas are rare, and have not been reported in the equine post operatively for analgesia. Histopathology of the left kidney veterinary literature. Renal adenomas are usually incidental revealed necrotising and abscessing pyelonephritis with severe findings on necropsy, and are noted to occur more often in destruction of medullary and cortical tissue. cattle and horses than in other species (Jubb et al. 1993). Serum biochemistries submitted one and 2 days post To the authors’ knowledge, this is also the first case report operatively revealed normal BUN and creatinine concentrations detailing serial monitoring of renal function of horses post (Day 1 post operatively: BUN = 230 mg/l, creatinine = 14 mg/l; nephrectomy. Both cases address adaptive changes in the Day 2 post operatively: BUN = 180 mg/l, creatinine = 13 mg/l). remnant kidney resulting from removal of a partially functional Haematology submitted the day after surgery revealed a kidney as a result of the presence of a papillary adenoma normal PCV and RBC count. A catheterised urine sample 2 days (Case 1) or from a nonfunctional kidney due to severe post operatively revealed isosthenuria (SG = 1.017), moderate pyelonephritis (Case 2). In Case 1, the horse was azotaemic for proteinuria, occasional epithelial cells/hpf (rr 0–5 epithelial approximately one month post operatively, underscoring the cells/hpf) and mild haematuria (4–6 erythrocytes/hpf). A repeat need to consider age-related changes and potential pre- urinalysis 10 days post operatively revealed isosthenuria existing renal damage prior to nephrectomy, as well as (SG = 1.017) and 1–3 epithelial cells/hpf. compensatory changes post operatively. The moderate elevation in serum creatinine suggests pre-existing bilateral Outcome renal disease despite a normal BUN and creatinine prior to surgery. Removal of 50% of the renal mass should not result One month post operatively, the mare was in good health with in a 100% elevation in serum creatinine assuming a normal no recurrence of pyuria. remnant kidney (Koeppen 2001). Relative to the maximal post 304 EQUINE VETERINARY EDUCATION / AE / July 2007

surgical value at Day 17, the serum creatinine decreased 78% deemed uncompromised based on prenephrectomy by Day 39 and 45.5% by month 4. Species differences may haematology and urinalyses. Nevertheless, these parameters exist with regards to the rapidity of the compensatory do not evaluate early or minor changes in GFR. Nuclear response post nephrectomy, and this may be reflected by the scintigraphy with 99mTc-DTPA is recommended as it is the only initially increased serum creatinine concentration in this case. available method for assessing split renal function. However, The urinary GGT to creatinine ratio at Days 17 and 26 post there is greater intrahorse variability using 99mTc-DTPA than operatively was not indicative of renal tubular damage. The using inulin as a marker of GFR (Matthews et al. 1992; Walsh urine specific gravity remained within the normal range and Royal 1992). Image-directed colour Doppler ultrasound preoperatively, but was isosthenuric up to Day 32 on post has been used to measure renal blood flow in normal horses, surgical follow-ups. With time, the ability of the remaining but detection of renal disease has not been reported (Gómez- kidney to concentrate normalised. Despite no observations of Ansón 1997; Hoffmann et al. 1997). The use of renal polydypsia in this case, the isosthenuria may also be attributed ultrasonography in both cases was essential in evaluating the to an increase in water consumption. The function of the architecture of the normal kidney, but not used to establish affected kidney did not appear to be disrupted by the renal renal function. Regardless of the age of the horse, we tumour, and ageing changes were not evident recommend preoperative evaluation of renal function prior to histopathologically. Further studies are needed in geriatric undertaking a nephrectomy. Ideally, evaluation of split renal horses to qualify age-related changes in the kidney, and to function is preferable. However, the availability and cost of the determine if functional changes precede morphological equipment required to perform nuclear scintigraphy limits its changes (McKeever 2002). However, this case demonstrates use in private practice. In the cases described, preoperative that removal of a kidney affected by local disease can safely be evaluation of the remnant kidney relied on serum BUN and pursued in aged horses as long as preoperative data reveal a creatinine and urine specific gravity. These methods require at functional remnant kidney. least a 50% loss of nephrons in order to detect abnormalities. In Case 2, normal serum creatinine and BUN Earlier detectors of renal insufficiency include fractional concentrations and normal RBC parameters were maintained. excretion of electrolytes, urinary GGT and urine cytological The chronicity of the disease process may have allowed the findings, which can be done easily in the field (Bayly et al. remnant kidney time to compensate for the lack of normal 1986; Edwards et al. 1989). nephron mass in the affected kidney. The urine specific Post operatively, the function of the remnant kidney in gravity was isosthenuric one day post operatively and human patients has been evaluated as preoperatively. remained so for at least 10 days. Osmotic diuresis may have Changes observed over time were an increased GFR, a contributed to this reduction in urinary concentrating ability, negligible increase in proteinuria and albuminuria, and a small the increased delivery of solutes and water to the remnant increase in blood pressure (Smith et al. 1985; Baudoin et al. nephrons resulting in a more dilute urine (Mackenzie et al. 1993; Kasiske et al. 1995). Renal and erythropoeitic function 2000). Case 2 did not have sufficient post operative data to was clinically preserved 2–5 years post operatively in 94% of evaluate resolution of isosthenuria. In previous reports on healthy feline kidney donors (Lirtzman and Gregory 1995). unilateral nephrectomy in horses, no significant renal With Case 1, a 50% loss of renal tissue was associated with complications were noted based on normal serum creatinine mild anaemia which resolved 4 months post operatively. and BUN 2 months post operatively (Trotter et al. 1984; In addition to assessing renal function post operatively, the Sullins et al. 1988; Jones et al. 1994). These values were pharmacokinetics and pharmacodynamics of renally neither reported nor evaluated in the early and late post metabolised and excreted drugs need to be re-established. operative period. The paucity of information with regards to such changes Preoperative evaluation of the remnant kidney has been requires frequent monitoring of serum drug levels in geriatric performed in man using biochemical assays, ultrasonography and nephrectomised patients and frequent dosage re- and scintigraphy (Ben-Haim et al. 2000; Mullerad et al. 2003). adjustments. Amikacin elimination in man following unilateral Baseline data in horses should include a complete blood nephrectomy is impaired, resulting in an increased risk of count, serum biochemistry panel, urinalysis and urine culture nephrotoxicity (Drozdzik et al. 2002). It is likely that with sensitivity. In Case 1, a urine culture was not performed pharmacokinetics in uninephrectomised horses will be due to lack of response to antibiotics. However, this diagnostic similarly affected. The use of potentially nephrotoxic drugs test is recommended at the onset of clinical signs, as requires frequent monitoring for renal insult and dysfunction. pyelonephritis can occur without cytological evidence of In Case 1, gentamicin and phenylbutazone administration was pyuria. Renal scintigraphy was not performed in either case as short-term, consisting only of 3 days. In Case 2, the nature of the disease process required removal of the aminoglycosides were not administered and only one dose of affected kidney for resolution of the problem. However, data phenylbutazone was administered post operatively. provided by scintigraphy would provide better evaluation of For horses with normal renal function, uninephrectomy the glomerular filtration rate (GFR), and may quantify the may be performed with a good prognosis for normal life as compensatory response in the unaffected kidney. Nuclear long as the remnant kidney does not become diseased. scintigraphy was not considered at the time of nephrectomy in Indications for performing unilateral nephrectomy include these cases as renal function in the unaffected kidney was severe unilateral pyelonephritis, unilateral nephrolithiasis and EQUINE VETERINARY EDUCATION / AE / July 2007 305

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