Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

Abstract

Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH 4 Cl-induced metabolic acidosis on the renal handling of Na + in male Wistar-Hannover rats (200-250 g). Chronic acidosis (pH 7.16 ± 0.13) caused a sustained increase in renal fractional Na + excretion (267.9 ± 36.4%), accompanied by an increase in fractional proximal (113.3 ± 3.6%) and postproximal (179.7 ± 20.2%) Na + and urinary K + (163.4 ± 5.6%) excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na + filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g) and pair-fed (225 ± 3.6 g) rats compared to the controls (258 ± 3.7 g). In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g) compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g). We suggest that altered renal Na + and K + handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial coupling and calcium transport in rats

“…Since we performed the present experiments using whole kidney structure, our studies were not specifically designed to determine the effects of metabolic acidosis on Na þ transport mechanisms along particular nephron tubule sites nor to correlate Na þ patterns with altered solute and water tubule handling. Nevertheless, previous experiments demonstrating altered renal sodium handling [25,26] may provide evidence for a reciprocal relationship between the level of efficiency of renal mitochondrial activity and ion tubule transport. Therefore, we hypothesize that the mild uncoupling and higher capacity for Ca 2þ accumulation represents an adaptation of the mitochondria to cope with conditions of oxidative stress and high cytosolic Ca 2þ , which are associated with NH 4 Cl toxicity in renal cells.…”

“…In this regard, we have previously shown that chronic metabolic acidosis, caused by NH 4 Cl feeding, leads to nephron hypertrophy and to a decreased watersalt reabsorption by the kidneys [1,25,26]. Since renal ion tubule transport is highly dependent on mitochondrial energy and because mitochondria have been implicated in a variety of metabolic disorders, we examined mitochondrial energy-linked functions in chronic metabolic acidotic rats.…”

“…Metabolic acidosis is also, associated with the down-regulation of organic anion pathways, Na-dependent inorganic sulfate and Na-phosphate cotransporters. Interestingly, despite these adaptive and appropriate changes, the proximal tubule exhibits a significant reduction in salt and water transport in response to metabolic acidosis [2,25,26,40]. A defect in salt and water reabsorption in the proximal tubule produces an increase in fluid delivery and increased hydroelectrolyte reabsorption in Henle's loop, the distal tubule and the collecting duct system.…”

Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia

“…24 or tubular function [25][26][27][28][29] which can result in an altered renal handling of sodium. [30][31][32][33][34][35][36]101 Surprisingly, while use of diuretics are well known to make the FeNa unreliable, [35][36][37][38] other drugs, such as amphotericin, that are known to cause proximal tubular damage may not. 39 Rarely liver disease can result in prerenal azotemia with an elevated FeNa because of sodium bicarbonate wasting from alkalosis 30 or alternatively because of loss of urea production that is necessary for water reabsorption and urine concentration.…”

“…Similarly, chronic (but not acute) respiratory acidosis is associated with a decrease in FeNa because of sodium bicarbonate generation and conservation by the tubules. 32 Chronic metabolic acidosis may also result in sodium wasting, 33,34 presumably because of a different mechanism where acidosis may disrupt active transport. Surprisingly, while use of diuretics are well known to make the FeNa unreliable, [36][37][38][39] other drugs, such as amphotericin, that are known to cause proximal tubular damage may not.…”