The contribution of residual nephrons within the chronically diseased kidney to urate homeostasis in man

Steele, Thomas H.; Rieselbach, Richard E.

doi:10.1016/0002-9343(67)90246-x

Cited by 109 publications

(69 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Maintenance of some degree of plasma urate homeostasis in subjects with -chronic renal failure is achieved by an increase in both intestinal uricolysis (1) and absolute urate excretion per residual nephron (2,3). The role of each component of the tubular bidirectional transport system for urate at different stages of disease has been assessed with the pyrazinamide suppression test (3,4).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Boumendil-Podevin¹,

Podevin²,

Richet³

1975

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Serum and urine from chronically uremic patients and normal individuals were subjected to gel filtration on Sephadex-G10. The effects of the eluted fractions on the uptake of urate and para-aminohippurate by isolated cortical tubules of rabbit kidney were investigated. According to the origin of the samples, one to three major groups of fractions inhibiting both urate and para-aminohippurate transport were disclosed. The first eluted group occurred for all the samples under study. The second one was demonstrated in both sera and urines from uremic patients but only in urines from normal individuals. The third one was exclusively detected in uremic sera and urines. Among all the compounds identified, only hippuric acid, eluted in the fractions of the second group, was capable of inhibiting the uptake of urate and para-aminohippurate in vitro. The concentration for which this inhibitory effect of hippuric acid occurred was in the range of that existing in uremic sera. Indoxyl sulfate, which accumulates to very high concentrations in uremic serum, could not be disclosed in the above-mentioned fractions. This is explained by the strong adsorption of this indole derivative to Sephadex gel. Potassium indoxyl sulfate, when tested in vitro at the concentration existing in uremic serum, substantially inhibited the uptake of both urate and para-aminohippurate. In normal subjects, ingestion of hippuric acid or potassium indoxyl sulfate significantly increased fractional urinary excretion of uric acid. On the basis of these results, it is suggested that progressive retention of hippuric acid, indoxyl sulfate, and other yet unidentified inhibitors may explain the gradual increase in urinary fractional excretion of urate This work was presented in part at a symposium on uremia sponsored by the International

show abstract

Section: Introductionmentioning

confidence: 99%

“…The role of each component of the tubular bidirectional transport system for urate at different stages of disease has been assessed with the pyrazinamide suppression test (3,4). However, the mechanism of the increased fractional urinary urate excretion in uremia has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Boumendil-Podevin¹,

Podevin²,

Richet³

1975

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…There is therefore no evidence for impaired uricosuric efficacy of benzbromarone in CsA-treated renal transplant patients. That benzbromarone is less effective in patients with low creatinine clearances most probably reflects diminished postsecretory reabsorption in the renal tubule such as occurs with increasing renal failure [15,16]. Postsectretory reabsorption is the presumptive site of action of uricosuric drugs [17].…”

Section: Discussionmentioning

confidence: 99%

Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study

Zürcher¹,

Bock²,

Thiel³

1994

Nephrology Dialysis Transplantation

View full text Add to dashboard Cite

Abstract.Patients on cyclosporin A (CsA) often develop hyperuricaemia and gout. In transplant patients the use of uricosuric drugs for treating hyperuricaemia may be preferable to allopurinol because of the known interaction of the latter with azathioprine. We therefore prospectively studied the uricosuric efficacy of 100 mg benzbromarone (Bbr;Desuric®) daily in 25 CsA-treated renal transplant patients with stable graft function and hyperuricaemia (> 359 umol/1 for females, >491 umol/1 for males).Benzbromarone decreased plasma uric acid from 579± 18 umol/1 to 313±24 umol/1 (mean + SEM; P< 0.001) and thereby normalized plasma uric acid in 21 of 25 patients. The remaining four patients had creatinine clearances between 21 and 25 ml/min, the lowest of the entire study group. Mean fractional clearance of uric acid increased from 5.4 ±0.4% to 17.2 ±1.0% (i><0.001). The relative decrease of plasma uric acid closely correlated with baseline creatinine clearance (r = 0.67; P<0.001). CsA trough values were not influenced. None of the patients experienced any significant side-effects. As an unexpected find-ing, urinary uric acid excretion increased from 2082+ 175 umol/24 h to 3233 ±232 umol/24 h after 4 weeks' treatment with benzbromarone.In conclusion, benzbromarone normalized plasma uric acid in all CsA-treated renal transplant recipients with a creatinine clearance > 25 ml/min. Due to its excellent efficacy and lack of significant side-effects, benzbromarone appears to be preferable to allopurinol in CsA-treated renal transplant recipients with a creatinine clearance over 25 ml/min.

show abstract

“…In unilaterally nephrectomized persons, the capacity for overall urate reabsorption appears to be well preserved, as indicated by fractional reabsorption values (after pyrazinamide pretreatment) greater than 98% (50). I n chronic renal insufficiency, an analogous situation appears to apply in that both total urate excretion per nephron and the I'yrazinamide-suppressible fraction attain supranormal values with progressive renal insufficiency until the GFR falls below 10 to 15 ml per minute (51). This increased urate excretion per nephron in chronic renal disease appears to occur independently of elevations in the plasma urate concentration.…”

Section: Thomas H Steelementioning

confidence: 96%

“…Ultimately of course hyperuricemia does occur as a consequence of the diminished renal mass, despite hyperactivity of urate transport systems within the residual functioning nephrons (51). I n end-stage chronic renal disease (GFR less than 10 to 15 ml per minute), it seems likely that both the secretory and reabsorptive transport of urate deteriorate (51). This failure of tubular transport processes in uremia has aroused considerable interest: Several studies have indicated that uremic sera may inhibit the uptake of hippurates (52) and urate (53) by renal tissue preparations.…”

Section: Thomas H Steelementioning

confidence: 99%

Renal excretion of uric acid

Steele

1975

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

I n earlier years of renal physiology study, the developnient of the inulin clearance for the estimation of the glomerular filtration rate (GFR) allowed a precise comparison between the excretion and filtration rates of many urinary solutes. Although it soon was realized that many members of a large group of weak organic acids are avidly bound by the kidney and undergo net tubular secretion, studies in several species including man indicated that the rate of uric acid excretion was far less than its rate of filtration. Even though the possibility was raised that polymerized or protein-bound aggregates of urate not amenable to glomerular filtration might exist in plasma (l), the prevailing opinion was that urate simply underwent complete glomerular filtration and partial tubular reabsorption. Extensive studies were reported in 1950 by Berliner et al (Z), in which urate titration procedures were performed in an attempt further to characterize urate reabsorption within the normal kidney. During the progressive infusion of urate, the difference between the rates of filtration and excretion of urate increased progressively. Berliner and his coworkers ultimately concluded that a maximum urate reabsorption rate probably exists in normal man, but that the ap- parent capacity for urate reabsorption is so great that it would not become fully saturated under normal conditions (2). Although Praetorius and Kirk (3) described a hypouricemic patient who demonstrated net urate secretion in 1950, the possible existence of a significant amount of tubular secretion of urate in man was not widely accepted. Subsequently, renewed interest in renal urate secretion occurred, largely as a result of work from the laboratory of the late Dr. Alexander Gutman. Gutman and Y u raised the question of the existence of urate secretion in man based on observations during clearance studies in gouty patients and normal persons (4). Even in their early reports, they hypothesized that large transtubular fluxes of urate might exist, for if secretion of urate did occur then the calculated net reabsorptive rates of urate would be too low. Subsequent observations elucidating the remarkable "paradoxical actions" of certain pharmacologic agents on urate excretion (5) and also the antiuricosuric effect of pyrazinamide (PZA) administration (6) raised the possibility that inhibition of the tubular secretion of urate could substantially reduce urate excretion. Although Gutman and his colleagues acknowledged that an enhanced rate of urate reabsorption could also have produced an antiuricosuric effect, they visualized that if virtually complete reabsorption of the filtered urate occurred within the nephron and if the urinary uric acid were derived primarily from

show abstract

The contribution of residual nephrons within the chronically diseased kidney to urate homeostasis in man

Cited by 109 publications

References 10 publications

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study

Renal excretion of uric acid

Contact Info

Product

Resources

About