Chronic hyperkalemic renal tubular acidosis induced by KCl loading

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.