The mechanism of renal
potassium wasting in
renal tubular acidosis associated with the
Fanconi syndrome (type 2 RTA) was investigated in 10 patients, each of whom had impaired proximal renal tubular reabsorption of
bicarbonate as judged from a greater than 15-20% reduction of renal tubular
bicarbonate reabsorption (THCO(3) (-)) at normal plasma
bicarbonate concentrations. When the plasma
bicarbonate concentration ([HCO(3) (-)]p) was experimentally increased to normal levels in three patients with a fractional
potassium excretion (C(K)/C(in)) of less than 1.0 during
acidosis, C(K)/C(in) and urinary
potassium excretion (U(K)V/C(in)) increased strikingly and concurrently with a striking increase in urinary
sodium (U(Na)V/C(in)) and
bicarbonate (U(HCO3-)V/C(in)) excretion. When [HCO(3) (-)]p was increased to normal levels in two patients with a C(K)/C(in) of greater than 1.0 during
acidosis and in whom U(Na)V/C(in) and U(HCO3-)V/C(in) were already markedly increased, C(K)/C(in) did not increase further. When [HCO(3) (-)]p was decreased to subnormal levels in a patient given
ammonium chloride, U(K)V/C(in), C(K)/C(in), and U(HCO3-)V/C(in) decreased concurrently. In the six patients in whom [HCO(3) (-)]p was maintained at normal levels (oral
alkali therapy) for 2 months or longer, C(K)/C(in) was directly related to the urinary excretion rates of
sodium and
bicarbonate, hence was directly related to the magnitude of reduction of THCO(3) (-) at normal [HCO(3) (-)]p; C(K)/C(in) was greater than 0.55 in all six patients and greater than 1.0 in four. In eight patients with classic RTA (type 1 RTA), proximal renal tubular reabsorption of
bicarbonate was largely intact as judged from a trivial reduction of THCO(3) (-) at normal [HCO(3) (-)]p. When [HCO(3) (-)]p was either increased from subnormal to normal levels, or decreased from normal to subnormal levels, U(HCO3-)V/C(in) remained essentially constant, and U(K)V/C(in) did not change significantly. When correction of
acidosis was sustained, U(HCO3-)V/C(in) remained a trivial fraction of that filtered, and C(K)/C(in) was consistently less than 0.55. These results provide evidence that renal
potassium wasting in type 2 RTA is physiologically separable from that in type 1 RTA and in part the result of a reduction in the rate at which the proximal tubule reabsorbs
bicarbonate and the distal delivery of supernormal amounts of
sodium bicarbonate. With an increased stimulus to distal
sodium reabsorption, indicated by the finding of
hyperaldosteronism, delivery to the distal nephron of supernormal amounts of
sodium with the relatively impermeant
bicarbonate anion would be expected to increase intraluminal negativity in the distal nephron, and as a consequence, increase
potassium secretion and promote renal
potassium wasting.