We report on a case of acute kidney injury in a patient with severe volume depletion from high ileostomy output and poor oral intake associated with hyperuricemia and hyperkalemia. The patient presented with similar features on three separate admissions. A conservative management approach was undertaken that included infusion of rasburicase, since the patient refused to undergo hemodialysis on each occasion. Rasburicase is a recombinant urate oxidase enzyme that converts uric acid to allantoin which is five to ten times more soluble than uric acid in urine, thereby enhancing urinary excretion. Rasburicase was administered each time and was followed by a prompt increase in urine output, rapid decrease in serum uric acid level, and recovery of renal function without the need for acute renal replacement therapy. We believe that rasburicase, with a molecular weight of 34 kDa, crossed the glomerular filtration barrier and entered the tubular fluid where it dissolved intra-tubular uric acid, thus relieving obstruction, thereby rapidly enhancing urine excretion and improving renal function. Based on this experience, we propose that rasburicase offers an alternative treatment for acute kidney injury in similar types of settings. To the best of our knowledge this is the first reported case in this situation.
Patients with ileostomies can acutely develop high volume output states that may be associated with acute kidney injury and life threatening electrolyte and acid base disorders [
A 59-year-old woman presented to the emergency room with nausea, vomiting and fatigue. She reported increased ileostomy output and decreased urine output. Her past medical history was significant for type 2 diabetes mellitus, hyperlipidemia and chronic obstructive airway disease. She had undergone right nephrectomy in 1995 for obstructive nephrolithiasis. Four months prior to this presentation she underwent a total abdominal hysterictomy and bilateral salpingo-ooperectomy for stage 1 A endometrial adenocarcinoma. Her hospital course was complicated by bowel perforation requiring partial ileal resection and ileostomy. Since creation of the ileostomy the patient has had two similar episodes described below, requiring admission to the hospital.
Six weeks prior to the current admission she presented to the emergency room with a 3 day history of nausea, vomiting, high ileostomy output, poor oral intake, and diminished urine output for one day. She denied fever, chills or abdominal pain. Her medications included pioglitazone, pravastatin, fenofibrate, aspirin, tiotropium and astelin nasal spray. Her admission blood pressure was 93/61 mmHg, heart rate 88 beats a minute and regular, temperature 35.9˚C and respiratory rate 16 breaths/min. Her oral mucous membranes were dry. The ileostomy was intact. Initial laboratory data revealed serum sodium (Na+) 128 mEq/L (128 mmol/L), potassium (K+) 7.0 mEq/L (7.0 mmol/L), chloride 82 mEq/L (82 mmol/L), and bicarbonate 30 mEq/L (30 mmol/L). Blood urea nitrogen (BUN) was 146 mg/dl (52.1 mmol/L), serum creatinine (SCr) 11.2 mg/dl (990.1 umol/L) (from a baseline value of 0.7 mg/dl, 61.9 umol/L), phosphorus 16.5 mg/dl (5.3 mmol/ L), and uric acid 24.4 mg/dl (1.45 mmol/L). No significant abnormalities were noted on EKG. An abdominal computed tomography (CT) scan revealed a kidney on the left with mild perinephric stranding and prominence of the collecting system, without hydronephrosis. She received 2.7 liters of normal saline intravenously and voided 30cc/ hr of urine. Hemodialysis was offered but the patient adamantly refused. At this point she received rasburicase 7.5 mg intravenously over 30 minutes (0.08 mg/kg/dose). Her urine output increased to 1300 cc (approximately 130 ml/hr) over the next 10 hours. Fifteen hours following rasburicase infusion, serum K+ decreased to 3.1 mEq/L (3.1mmol/L), BUN declined to 116 mg/dl (41.4 mmol/L) and SCr 8.67 mg/dl (766.4 umol/L). The serum uric acid level had decreased to 5.4 mg/dl (0.32 mmol/L) within 24 hours. White blood cell count decreased from an admission value of 7.1 × 103/mL3 to 2.1 × 103/mL3 and spontaneously recovered. The patient was continued on intravenous hydration throughout her ten day hospital stay. Her ileostomy output decreased with diphenoxy/ atropine. She was discharged home with a SCr of 1.27 mg/dl (112 umol/L).
Two weeks later, routine laboratory tests revealed a serum of Na+ 123 mEq/L (123 mmol/L), K+ 8.5 mEq/L (8.5 mmol/L), chloride 88 mEq/L (88 mmol/L), bicarbonate 21 mEq/L (21 mmol/L), BUN 80 mg/dl (28.6 mmol/L) and SCr 6.37 mg/dl (563.11 umol/L). The patient was again hospitalized with symptoms of nausea, vomiting, decreased oral intake and high ileostomy output. Vital signs revealed blood pressure 104/73mmHg and heart rate 112 beats/min. The physical exam was significant for dry mucous membranes. Repeat laboratory data revealed serum Na+ 130 mEq/L (130 mmol/L), K+ 8.0mEq/L (8.0 mmol/L), chloride 88 mEq/L (88 mmol/ L), bicarbonate 21 mEq/L (21 mmol/L), SCr 6.30 mg/dl (556.9 umol/L), phosphorus 6.6 mg/dl (2.1 mmol/L), and uric acid 12.1 mg/dl (0.72 mmol/L). Renal sonogram showed the single left kidney with no evidence of hydronephrosis. She was given 2 liters of intravenous normal saline along with three doses of sodium polystyrene sulfonate (30 mg) over4 hours. No increase in urine output was noted. The patient again refused hemodialysis. Rasburicase 11.5 mg (0.13 mg/kg/dose)was infused over 30 minutes. Urine output increased to 920 ml over the next 24 hours. Fifteen hours post rasburicase infusion, serum K+ was 4.8 mEq/L (4.8 mmol/L), BUN 66 mg/dl (23.6 mmol/L) and SCr 6.23 mg/dl (550 umol/L). Serum uric acid level had decreased to 1.8mg/dl (0.11 mmol/L). Neutropenia evolved which required a single subcutaneous dose of filgastrim (Neupogen) 300 microgram. The patient was discharged after a 7 day hospital stay with a SCr of 1.56 mg/dl (137.9 umol/L) and a normal white blood cell count.
On the current admission, blood pressure was 113/68 mmHg, heart rate 113 beats/min, temperature 35.4˚C, and respiratory rate 18 breaths/min with O2 saturation of 98% on room air. Mucous membranes were dry. Cardiovascular, pulmonary and neurological examinations were unremarkable. Abdominal examination revealed an intact ileostomy, no tenderness, and normal bowel sounds. Laboratory tests showed serum Na+ 132 mEq/L (132 mmol/L), K+ 8.1mEq/L (8.1 mmol/L), chloride 95 mEq/ L (95.0 mmol/L), bicarbonate 17 mEq/L (17.0 mmol/L), SCr 8.0 mg/dl (707.2 umol/L), phosphorus 7.2 mg/dl (2.3 mmol/L) and uric acid 18.6 mg/dl (1.1 mmol/L). The renal sonogram was unchanged. The patient was given three doses of sodium polystyrene sulfonate (30 gm), and calcium gluconate 1 gm and 50% dextrose (15 gm) and 10 units of regular insulin intravenously. Five liters of normal saline were infused over the initial 24 hours with no urine output. She again refused hemodialysis. A single intravenous dose of rasburicase 6 mg (0.08 mg/kg/ dose) was given. Within 24 hours, the urine output increased to 50ml/hr and serum chemistry showed K+ 3.2 mEq/L (3.2 mmol/L), BUN 76 mg/dl (27.1 mmol/L), SCr 6.67 mg/dl (589.6 umol/L) and uric acid of 4.7 mg/dl (0.28 mmol/L). The white blood cell count decreased from 6.4 × 103/mL3 to 2.5 × 103/mL3 s and recovered spontaneously. She continued to receive intravenous hydration until her sixth hospital day at which point she underwent reversal of the ileostomy. The patient was discharged home 1 month later with a SCr of 0.83 mg/dl (73.4 umol/L).
We report on a case of acute kidney injury in a patient with severe volume depletion from high ileostomy output associated with hyperuricemia and hyperkalemia on three separate admissions. A conservative approach was taken in keeping with the patient’s refusal to undergo hemodialysis on each occasion. Administration of rasburicase was followed by a dramatic decrease in serum uric acid level, with a concomitant increase in urine output and significant improvement in renal function on each occasion, alleviating the need for hemodialysis. We submit that rasburicase was responsible for this course of events.
Acute urate nephropathy is most commonly encountered in patients with large tumor burdens who undergo chemotherapy and where there is rapid destruction of tumor cells, the so called “tumor lysis syndrome” [
A number of mechanisms have been proposed by which uric acid may contribute to acute kidney injury. First, the markedly elevated serum uric acid level results in supersaturation of the tubular fluid with precipitation of uric acid and obstruction of the tubular lumina. From micro puncture studies it is known that uric acid precipitates mainly in the distal tubule where uric acid concentration is high and the environment is acidic [
Patients with well-functioning ileostomies under steady state conditions can have a 7% to 11% decrease in total body sodium and water [
Rasburicase is a recombinant urate oxidase enzyme that converts uric acid to allantoin which is five to ten times more soluble than uric acid in water, thereby enhancing urinary excretion of this product of nucleic acid degradation [
Acute kidney injury associated with hyperuricemia is traditionally treated with volume expansion and urinary alkalization which favors solubilization of uric acid to urate in the urine. This helps to relieve intra-tubular obstruction. This is based on animal studies where high tubular fluid flow, whether induced by solute or water diuresis, was the primary mechanism of protection in acute urate nephropathy, with alkalization playing a lesser role [
In conclusion, we report on a case with acute kidney injury associated with high ileostomy output and secondary hyperuricemia which responded to rasburicase infusion. On three separate occasions, rasburicase infusion led to a dramatic decrease in serum uric acid level over a short period of time, with rapid improvement in renal function. Hemodialysis was obviated in keeping with the patient’s request. Based on this limited experience, we propose that rasburicase offers an alternative treatment for acute kidney injury in similar types of settings. Additional clinical studies are needed to confirm this observation.