Experimental Urate Nephropathy: Studies of the Distribution of Urate in Renal Tissue

Epstein, F H; Pigeon, G

doi:10.1159/000179328

Cited by 31 publications

(7 citation statements)

References 10 publications

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“…Previous work from our laboratory has confirmed that the major tubular site of urate deposition is the collecing duct (14). By inference from studies of renal tissue urate content during hyperuricemia, this is also the nephron segment of highest uric acid concentration (18,20). The effect of high V would be to lower the concentration of urate within the collecting duct enhancing its solubility and to rapidly "flush" any precipitated urate material from this tubular segment.…”

Section: High-flow Water Diuresis (Group Vmentioning

confidence: 82%

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

Conger¹,

Falk²

1977

J. Clin. Invest.

139

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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

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Section: High-flow Water Diuresis (Group Vmentioning

confidence: 82%

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

Conger¹,

Falk²

1977

J. Clin. Invest.

139

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“…Firstly, the formation of uric acid crystals within the tubules where the pH becomes progressively more acid is prevented. Secondly, in the medulla, where sodium concentration is high, precipitation of sodium urate with the resultant inflammatory response it elicits is avoided (Epstein and Pigeon, 1964). An example where this mechanism breaks down may be the instances of uric acid nephropathy which occur in lymphoproliferative disorders when the kidney has to cope with a large uric acid load (Passwell, Boichis, and Cohen, 1970).…”

Section: Discussionmentioning

confidence: 99%

Fractional excretion of uric acid in infancy and childhood: Index of tubular maturation

Passwell¹,

Modan²,

Brish³

et al. 1974

Archives of Disease in Childhood

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Passwell, J. H., Modan, M., Brish, M., Orda, S., and Boichis, H. (1974). Archives of Disease in Childhood, 49, 878. Fractional excretion of uric acid in infancy and childhood: index of tubular maturation. Normal newborns had a low glomerular filtration rate measured by creatinine clearance which progressively increased to reach adult levels by one year of age when corrected for surface area.There was also an increased fractional excretion of uric acid (34*6%±11 2 SD).Progressive maturation of this tubular function was observed within the first year of life. Thereafter, stable levels approaching adult levels of excretion were maintained. Linear regression functions of log-transformed values of fractional excretion of uric acid by weight were fitted separately to the newborns, infants < 1 year, and children aged 1 to 7 years. The 3 groups were found to constitute three distinct populations with regard to both the slope of the regression lines and the scatter of values about the line, which decreased significantly from the youngest to the oldest group. In low birthweight infants both glomerular and tubular maturation, as evidenced by these parameters, were related to age rather than to weight.It is suggested that the large urinary uric acid load excreted in the first days of life is facilitated by the concomitant deficiency of acidification and concentration of urine.Pink stained diapers due to urate deposition is a common occurrence in the newborn nursery. The presence of large amounts of urates in the renal tissue of neonates as 'urate infarcts' is also a well known incidental finding at necropsy. These two facts were impressed upon us by a routine survey in newborns, where large amounts of uric acid crystals were found in the urinary sediment. Accordingly, we undertook this study to investigate the excretion of uric acid by the kidney of the normal newborn and the progressive maturation of this function during the first year of life. Male infants predominated because of the difficulty of collecting urinary specimens in the females. No sex differences were found in the various tests of renal function. All the newborn infants were products of normal pregnancies and were born with Apgar scores of 10. Informed consent was obtained for all the studies.Renal studies. Disposable urine collectors were used. The infants were under constant supervision throughout by a special nurse in order to assure complete urine collections. Collections were started 72 hours after birth and the first urine was discarded. Collection thereafter proceeded for 24 hours in newborns. The end point was taken as the last time urine was passed as noted by the special nurse. This last fresh specimen was used for pH examination (pH meter 29 Radiometer) and routine urine analysis. In older infants and in children, at least 3 complete timed specimens were collected for clearance calculations. Venous blood for blood chemistry was withdrawn at the end of the collections. 878 on 12 May 2018 by guest. Protected by copyright.

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“…Something of the kind might be invoked to explain the concentration of urate in medulla and papilla to levels exceeding that in renal cortex (50,51). However, there is at present no reason to suspect that the processes involved are large in magnitude or that they are the sites of drug action.…”

Section: Resultsmentioning

confidence: 99%

Pyrazinoate Excretion in the Chimpanzee. RELATION TO URATE DISPOSITION AND THE ACTIONS OF URICOSURIC DRUGS

Fanelli¹,

Weiner²

1973

J. Clin. Invest.

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A B S T R A C T These experiments were designed to define the renal disposition of pyrazinoic acid in a nonhuman primate that is phylogenetically close to man and to relate this to the effects of pyrazinoate on urate excretion. The renal clearance of pyrazinoate was -almost always greater than the simultaneous glomerular filtration rate at plasma concentrations ranging from 1.9 to 960 Fg/ml. Some inhibitors of tubular secretion, probenecid, MK-282 (an experimental, potent uricosuric drug), p-aminohippurate, iodopyracet, sulfinpyrazone, and mersalyl, reduced clearances of pyrazinoate to values far below filtration rate. Chlorothiazide, allopurinol, and salicylate did not. The clearance of pyrazinoate was not influenced by changes in urine flow. It is concluded that pyrazinoate is actively secreted and actively reabsorbed.Pyrazinoate had a dual effect on urate excretion. At concentrations in plasma less than 10 ug/ml there was a concentration related fall in urate/inulin clearance ratio, reaching values of 10-20% of control. Over the range of 10-100 Ihg/ml in plasma, the clearance of urate remained maximally depressed. At higher concentrations of pyrazinoate there was a concentration related increase in urate/inulin clearance ratio such that at pyrazinoate levels above 600 /tg/ml a definite uricosuric response was obtained. Prior administration of pyrazinoate to give plasma levels of 20-140 /Ag/ml completely or almost completely prevented uricosuric respones to probenecid, PAH, chlorothiazide, and sulfinpyrazone. lodopyracet, mersalyl, salicylate and N-acetyl-4-dibutylsulfamoyl-3-trifluoromethylbenzenesulfonamide (MK-282) retained significant uricosuric action, but the activities were prob-

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Experimental Urate Nephropathy: Studies of the Distribution of Urate in Renal Tissue

Cited by 31 publications

References 10 publications

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

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

Fractional excretion of uric acid in infancy and childhood: Index of tubular maturation

Pyrazinoate Excretion in the Chimpanzee. RELATION TO URATE DISPOSITION AND THE ACTIONS OF URICOSURIC DRUGS

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