Effect of para-aminohippurate on renal transport of oxalate

Abstract

The renal handlinig of oxalate was examinied by free-flow micropuncture, intratubular microinijectioni, an(d droplet precessioni techniques in the rat. After the stustained i.v. infusionj of [14C]oxalate, the fractional (Ieliverv of oxalate from the early portions of the proximal tul)ule was 120.1+4.4%, indicating net secretioin. Fractionial delivery rates from the late proximal tubtule (124.6+6.1), distal tubule (120.9+2.9), and final urine (126.2+2.9%) were not different froml that of the early proximal tubule. Direct intratubular miicroinjections of oxalate into the early proximal tubule anid late proximal tubule yielded urinary re-coverv rates of 85+3% and 101+2%, respectively, suggesting that oxalate absorption does occur in the mlid-portionis of the proximal tubule. Droplet pre-cessioni studies confirmed a secretorv flux for oxalate. In contrast to oxalate, para-aminlohippurate (PAH), the more traditional marker for organic acid transport, was secreted in the late portions of the proximal tubule and in large measure at a site between the late proximal and distal tubules, presumably the pars recta. Probenecid inhibited PAH secretion but was w%ithout effect on net oxalate transport, oxalate absorption , or oxalate secretion. These studies demiionistrate that net oxalate secretion ocecurs in the earlx portions of the proximlal convoltuted tubule, uinidergoes bidirectional trainsport of approxi-m-atel e(qulal milagnittude in later segmiienits of the proximual tubtule, aind problalyl is not transported in imiore distal nephroni sites. The secretory mechaniism for oxalate differs fromn that of PAH in that it is located in a differenit segment of the nephroni and is not inhibited by probenecid. These differences These studies wvere performiied wvhile Dr.

Renal Handling of Oxalate

“…For comparison, data of distal punc tures and of ipsilateral urine are included. It is apparent that fractional recovery of uC-oxalate increases along the proximal convolution and exceeds unity by some 10% at the end of this segment, thus in dicating proximal net secretion of oxalate and confirming previous reports [13,20], At present we favor the view that net secre tion of oxalate occurs in the proximal tubule probably including the pars recta. The ab solute values of the net secretion of oxalate found in the anesthetized rat, however, are of little importance since the secretion might well be influenced by the anesthesia itself, by the state of hydration [5] and by several other factors.…”

“…This led the authors to conclude that oxalate secretion is either limited to the late distal nephron or to nephron populations not accessible to usual micropuncture techniques. In contrast to this study, another group [13,20] showed proximal recoveries of oxalate significantly exceeding unity (1.2-1.3) and very similar values for the fractional excretion in urine. These data, therefore, were interpreted to indicate proximal net secretion of oxalate.…”

“…The reason for the differences between the above data is unresolved. It should be point ed out, first of all, that the quantitative dis crepancy between the two groups is not more than 30-40%, and that the net secre tion in rat is only 10-30% of the filtered load [5,8,9,13,20], Secondly, it is clear that the analysis of 14C and 3H concentra tions in small samples of tubule fluid in volves errors which largely depend on the absolute amount of radioactivity in the tu bular fluid sample. This problem can be avoided by using large doses of 14C-oxalate.…”

Oxalate: From the Environment to Kidney Stones

“…As demonstrated in dogs (132), humans (133), sheep (134), and rats (135), the bulk of body oxalate is excreted by kidneys, partially via glomerular fi ltration and partially via active secretion in the proximal parts of the nephron. In addition to secreting oxalate, proximal tubules are also sites of limited oxalate reabsorption (135,136), whereas the distal parts of a nephron are not involved in oxalate transport (137). Detailed studies on rat kidney proximal tubules indicated the presence of a low-affinity, high-capacity excretory system for o x a l a t e , w h i c h c a n b e i n h i b i t e d b y pchloromercuribenzoic acid (PCMB), cyanide, indacrinone (MK-196), furosemide, and paminohippurate (PAH) (137,138).…”

“…In addition to secreting oxalate, proximal tubules are also sites of limited oxalate reabsorption (135,136), whereas the distal parts of a nephron are not involved in oxalate transport (137). Detailed studies on rat kidney proximal tubules indicated the presence of a low-affinity, high-capacity excretory system for o x a l a t e , w h i c h c a n b e i n h i b i t e d b y pchloromercuribenzoic acid (PCMB), cyanide, indacrinone (MK-196), furosemide, and paminohippurate (PAH) (137,138). However, these and other studies suggested that more than one secretory system, with different affi nities for oxalate, may be responsible for oxalate handling in mammalian kidneys (129, 137, and 138).…”