Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy.

Abstract

A B S T R A C T Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephropathy. Various prehyperuricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuricemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV Portions of this study appeared in abstract form in the

Renal Function in Rats with Acute Medullary Injury

“…These features were probably due, at least in part, to the severity of the injury reaction and relatively slow induction of the lesion, since Conger et al have demonstrated severe oliguric renal failure fol lowing the administration of oxonic acid and a massive infusion of lithium urate [Conger and Falk, 1977;Conger el a i, 1976]. In the present study, histopathologic changes were most marked in the medullary portion of the kidney.…”

Urate Deposits in the Renal Medulla

“…An alkaline diuresis may reverse acute renal insufficiency developing in an over-producer of urate fol lowing inadvertent fluid restriction [13]. It has also been shown experimentally that a high tubular fluid flow is the most important mechanism of protection in acute urate nephropathy in rats [14]. Urine concentration and flow rate would also be expected to be an important contributory factor in an area with a subtropical climate such as Bris bane.…”

Reversal of Severe Volume Deplete Acute Kidney Injury by Rasburicase

“…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 [17]. Rasburicase rapidly lowers serum uric acid by converting it to a soluble compound allantoin, thereby dramatically decreasing proximal tubular uric acid excretion and preventing its precipitation in the tubular lumen.…”