Chronic hyperkalemia is a potential renal acidosis-producing factor by virtue of its ability to suppress renal HCO-3 reabsorption and ammoniagenesis. However, this potential has not been tested directly, as reported models of chronic hyperkalemia entail independent renal acidosis-producing conditions, e.g., mineralocorticoid deficiency; nephron loss; antikaliuretic agents known to inhibit H+ secretion. Since even massive K+ loading has little effect on plasma [K+] in intact animals, we performed chronic K+ loading on adrenalectomized dogs maintained on fixed steroid replacement and reduced dietary PO4 to limit urine buffer without hypophosphatemia. This resulted in chronic stable hyperkalemia ([K+](p) 6.7 ± 0.3 meq/liter) and hyperchloremic metabolic acidosis (Δ[HCO-3](p) -4.6 ± 0.4 meq/liter, P < 0.001; Δ[H+](p) +7 ± 0 neq/liter, P < 0.01). Net acid excretion decreased (ΣΔNAE -37 ± 8 meq, P < 0.01) predominantly because of decreased NH+4 excretion (ΣΔNH+4 -26 ± 5 P < 0.01), which, in turn, presumably resulted from a decreased availability of NH3 for titration of secreted H+, since urine pH decreased. Correction of hyperkalemia and acidosis occurred when PO4 was substituted for Cl- without change in K+ loading, or when K+ loading was discontinued. The finding of an inverse relation between [HCO-3](p) and [K+](p) is also consistent with an acidosis-producing contribution of an extrarenal shift of H+ from cells to extracellular fluid attendant on increased cellular K+ content induced by KCl loading. This study represents the first demonstration of renal tubular acidosis induced by K+ loading in any species without intrinsic renal disease, drugs, or mineralocorticoid deficiency. The findings in this study also demonstrate that in K+-loaded dogs with fixed steroid supply the nature of the coadministered anion is a critical determinant of K+ adaptation.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - Jan 1 1983|
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