Renal excretion of uric acid

Abstract

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

Decreased renal excretion of uric acid following diuretic administration in rats.

“…The rat is a useful animal for evaluating drug effects on uric acid excretion because the net flux in the tubular excretory transport of uric acid is reabsorptive, although the fractional excretion of uric acid is obviously higher than that in man (9)(10)(11)(12)(13). Thus, we utilized rats as the animal for evaluating the action of diuretics on the uric acid transport system.…”

Secondary gout in hemoglobinopathies: Report of two cases and review of the literature

“…Another explanation for the infrequency of gout may involve compensatory renal mechanisms of urate excretion. It is generally assumed that urate is freely filtered at the glomerulus; alarge proportion of this filtered load (probably greater than 80%) is reabsorbed at the proximal tubule (17). Subsequently, both tubular secretion and further reabsorption occur along the distal nephron (17,18).…”

Vergleich Der Klinischen Wirksamkeit Verschiedener Allopurinol- Zubereitungen Auf Die Hyperuricaemie

“…Es stellt sich bei Gesunden innerhalb von 7 bis 10 Tagen ein Plasmaharnsäurespiegel von durchschnittlich 3,1 mg/dl sowie eine mittlere renale Ausscheidung von 330 mg/dl ein (77,140,152,211). (189,219,220). GRÜBNER ( 136 (136,159,192).…”

“…Selbst ihre Zuordnung im Rahmen des Drei-Komponenten-Systems aus Filtration -Rückresorption -und tubulärer Sekretion ist unsicher. Nach Ansicht mehrerer Autoren (15,103,123,141,168,181,189,205,219,235,253) (15,33,80,141,160,163,188,213,256). (80,88,170,181,186).…”

“…(51, 136). Die renale Clearance ist bei Gichtpatienten durchschnittlich geringer, die Bereiche der Werte von Gesunden und Patienten mit familiärer Hyperuricaemie überschneiden sich jedoch (51, 136, 189).Bei der renalen Harnsäureausscheidung sind 3 Mechanismen beteiligt, die glomuläre Filtration, die tubuläre Reabsorption und die tubuläre Sekretion(23, 103,140,168,189,219,253).Oie Harnsäure wird glomulär zu einem hohen Prozentsatz, möglicherweise vollständig (103, 168, 189) filtriert. Eine vollständige Eiltration ist nur möglich, wenn keine Bindung an Plasmaproteine vorliegt.…”