Uphill Transport of Urea in the Dog Kidney: Effects of Certain Inhibitors*

Abstract

Summary. To study the renal medullary transport and accumulation of urea in dogs independent of water transport, we obliterated the medullary electrolyte gradient by a sustained ethacrynic acid diuresis. Infusions of urea were also given at various rates to vary urinary urea concentration. In the steady state, the kidneys were removed, and slices were analyzed for water, urea, and electrolytes. In every experiment in 15 dogs over a range of urinary urea concentration from 19 to 230 mmoles per L and urine flow from 0.5 to 9.7 ml per minute per kidney, an intrarenal urea gradient persisted, and urinary urea concentration was always lower than papillary water urea concentration. The magnitude of this uphill urinary-papillary gradient (mean + SE = -21 + 2.9 mmoles per L) was not affected by hemorrhagic hypotension or a nonprotein diet.In 12 additional experiments begun similarly, inhibitors were infused into one renal artery. Both iodoacetate, an inhibitor of anaerobic glycolysis, and acetamide, an analogue of urea, markedly and significantly reduced both the intrarenal urea gradient and the uphill urinary-papillary gradient. In contrast, cyanide, an inhibitor of oxidative metabolism, had no observable effect on the urea gradients. The data are best explained by postulating an active transport system for urea in the medullary collecting duct deriving its energy from anaerobic glycolysis.

Active sodium-urea counter-transport is inducible in the basolateral membrane of rat renal initial inner medullary collecting ducts.

“…The possibility that a loop diuretic could induce active urea transport was initially suggested by a tissue-slice study of dog kidneys that reported that the intrarenal infusion of ethacrynic acid induces active urea reabsorption in the inner medullary tip (29). In the present study, we directly demonstrated that furosemide induces active urea reabsorption in rat initial IMCDs.…”

Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse

“…Five hydropenic animals which were given no drug were used to obtain control levels of urea from cortex to papillary tip. These data were reported elsewhere as part of another study (11), but they are utilized here as controls because the experimental preparation and methods of analyses were identical with those of the present study.…”

“…This could be explained either by a passive washout of APAP and urea at high rates of tubular urine flow, as suggested by Ullrich and Jarausch (22), or by a decreased rate of collecting duct reabsorption because of the fall in tubular concentration of urea or APAP occurring with water diuresis (11 ). These effects of hydration in diminishing the renal gradient for APAP suggest that dehydration as well as the amount of analgesic compound consumed may have a bearing on the development of the renal lesions.…”

Urea transport in the proximal tubule and the descending limb of Henle

“…A number of studies (7,11,12,(18)(19)(20)(21)(22) have shown that under certain conditions papillary tissue water concentration of urea is greater than in the final urine. This had lead to the postulation that the medullary collecting duct is capable of active transport of urea.…”