From the Department of Pediatrics, Manipal Hospital, 98, Rustom Bagh, Airport Road, Bangalore 560 017, India.
Reprint requests: Dr. Arvind Shenoi, Department of Pediatrics, Manipal Hospital, 98, Rustom Bagh, Airport Road, Bangalore 560 017, India.

Manuscript Received: July 7, 1999;
Initial review completed: July 30, 1999;
Revision Accepted: September 20, 1999

Acute renal failure in neonates has been usually reported from our country following asphyxia and sepsis(1). We report here a neonate who presented to us with acute renal failure due to an unusual cause, namely hyperuricemia.

A sixteen-day-old male infant presented with vomiting, poor feeding and rapid respiration of 24 hours duration. The baby was anuric for 16 hours prior to admission. The baby was the first child born of non-consaguineous marriage. He was born full term through spontaneous vaginal delivery with a birth-weight of 2.75 kgs. There was no significant antenatal or natal history. There was no history of birth asphyxia. The baby was exclusively breast-fed and was not on any medications.

On admission the baby was sick–looking, acidotic and dehydrated. He weighed 2.3 kg, heart rate was 150/min, respiratory rate was 68/min and BP was 80/50 mm Hg. The extremities were cold and there was delayed capillary refill. The cardio vascular and chest examiation was within normal limits. The urinary bladder and kidneys were not palpable. The child was given fluid resuscitation. Investigations revealed: WBC-15,400 cells/cumm with a differential of P 80%, and L16%, Hb 12.9 g/dl, platelets -325,000/cumm, BUN 154 mg/dl, serum creati-nine - 6.5 mg/dl, serum sodium - 145 mEq/L, serum potassium - 3.8mEq/L, serum bicarbo-nate - 2.4 mEq/L, serum calcium - 7.5 mg/dl, serum uric acid - 33 mg/dl and serum phos-phorus - 4.5 mg/dl. The arterial blood gases revealed decompensated metabolic acidosis. Urine was examined when the baby started passing urine 24 hours after admission which showed albumin trace, pH of 6, and RBC 5-10/hpf. It was studded with uric acid crystals. The fractional urinary excretion of sodium was 10%, uric acid was 45% and urine calcium/creatinine ratio on random sample was 0.14. The X-ray abdomen did not show any radiopaque densities. Renal ultrasound revealed small renal calculi in calyceal area on right side, normal sized kidneys with no dilatation of pelvicalyceal system. Tests to confirm partial hypoxanthine-guanine phosphoribosyl transferase deficiency could not be carried out as they were not available. The blood, urine and cerebro-spinal fluid were sterile on culture.

The baby was given peritoneal dialysis 50-80 ml/cycle (dwell time 20-30 minutes) for 72 hours within next 3-4 days. The renal functions gradually returned to normal (serum creatinine 0.5 mg) within two weeks. At that time, serum uric acid level was 4.0 mg/dl. Two weeks later, the baby had normal renal functions and serum uric acid levels on oral therapy with allopurinol (5 mg/kg/dose) which was started on day 5 after admission. On follow up at 3 months the infant has a small calculus in the right renal pelvis, is growing well and is still on allopurinol.

Discussion

The common pre-renal causes of acute renal failure in a neonate are asphyxia, sepsis and hypovolemia(1). Post-renal failure can occur following posterior urethral valves. Intrinsic renal failure is rare and can occur following renal vein thrombosis, or exist as in renal dysplasia. Uric acid is a nephrotoxin and causes intrinsic renal failure.

Uric acid appears to be nearly completely filtered by glomerular membrane. Reabsorption of filtered uric acid occurs early in the proximal convoluted tubule. Tubular secretion of uric acid occurs in the distal convoluted or proximal straight tubule, which is inhibited by pyrazina-mide. Post-secretory reabsorption of uric acid also occurs. Up to about twice the normal plasma concentrations of creatinine, the plasma concentration of uric acid increases approxi-mately in parallel with creatinine. At this point, the increase in plasma concentration of uric acid flattens off, despite a further reduction in glomerular filtration rate (GFR), so that the concentration of uric acid in the plasma is still only twice normal even in individuals with end-stage uremia(2). Our patient had a very high level of serum uric acid level of 33 mg/dl, not explained by the fall in GFR alone.

In premature and term infants, there is a dramatically elevated fractional excretion of uric acid compared with adults (70% at 29-31 weeks, 38% at term, and 7% in adults)(3). In adults but not in children, measurement of the ratio of urinary uric acid to creatinine concentrations is useful in diagnosing acute urate nephropathy, the individuals with the ratio of greater than 1.0 are at increased risk(4). In adults with acute renal failure, a urine uric acid/urine creatinine ratio greater than 1.0 is found only with urate nephropathy. However, this test cannot be employed in children since this ratio normally exceeds 1.0 during childhood. Enhanced renal capacity for urate secretion during childhood may account for the rarity of gout in children.

The most common etiology for hyper-uricemia in children is rapid turnover of nucleoproteins in patients with lymphoma or leukemia(5,6). Acute urate nephropathy may also complicate partial hypoxanthine -guanine phosphoribosyl transferase deficiency(7), perinatal asphyxia(8), or status epilepticus(9). Hyperuricemia is also one of the components of Lesch-Nyhan syndrome.

In hyperuricemia, oliguric acute renal failure results from renal tubular obstruction by the precipitation of un-ionized uric acid in collecting tubules. There is little interstitial infiltration and the pathologic features of acute urate nephro-pathy are reversible.

The management of acute urate nephropathy consists of aiming at high urine rates, alkalinization of urine and use of allpurinol to reduce filtered urate load. Allopurinol is an inhibitor of xanthine oxidase, and renal failure secondary to xanthine preceipitation has been observed rarely during allopurinol therapy. Dialytic treatment may have to be resorted to both for treatment of acute renal failure and for clearance of uric acid. The clearance of uric acid is better with hemodialysis compared to peritoneal dialysis. However, we resorted to peritoneal dialysis in view of the ease and expertise we have in the procedure. Uricolytic therapy with intravenous administration of uricase appears to hold promise for the future.

Our patient had no other cause of acute renal failure other than hyperuricemia. The urine was studded with uric acid crystals. The ultra-sonogram revealed radiolucent calculi in right kidney. The patient improved with hydration, alkalinization, allopurinol and dialytic therapy with reversal of acute renal failure. The exact etiology of hyperuricemia in this patient is unclear. Partial hypoxanthine–guanine phosphoribosyl transferase deficiency is a possibility but could not be confirmed. Acute urate nephropathy should be suspected in unexplained neonatal acute renal failure with markedly elevated serum uric acid con-centrations and abundant urate crystals in the urinary sediment.

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2. Cameron JS, Moro F, Moro H, Simmonds HA. Uric Acid and the kidney. In: Oxford Textbook of Clinical Nephrology, Eds. Davison AM, Cameron S, Grunfeld JP. 2nd edn. Oxford, University Press, 1998; pp 1159-1173.

3. Stapleton FB. Renal uric acid clearnace in human neonates. J Pediatr 1983; 103: 290-294.

4. Kelton J, Kelly WN, Holmes EW. A rapid method for the diagnosis of acute uric acid nephropathy. Ann Intern Med 1978; 128: 612-615.

5. Cohen LF, Balow JE, Magrath IT. Acute tumor lysis syndrome, a review of 37 patients with Burktt’s lymphoma. Am J Med 1980; 68: 486-491.

6. Kanwar YS, Manaligod JR. Leukemic urate nephropathy. Arch Pathol 1975; 99: 467-472.

7. Lorentz WB, Batron BK, Trillo A. Failure to thrive, hyperuricemia and renal insufficiency in early infancy secondary to partial hypoxanthine-guanine phosphoribosyl transferase deficiency. J Pediatr 1984; 104: 94-97.

8. Ahmadain Y, Lewy PR. Possible urate nephropathy of the newborn infant as a cause of transient renal insufficiency. J Pediatr 1977; 91: 96-100.

9. Warren DJ, Leitch AG, Legette RJE. Hyperuricemic acute renal failure after epileptic seizures. Lancet 1975; 2: 385.