Studies to determine the basis for hyperkalemia in recipients of a renal transplant who are treated with cyclosporine

Abstract

Hyperkalemia is commonly encountered in patients who receive a renal transplant and the immunosuppressive drug, cyclosporine. There is also a high incidence of hypertension (which is thought to be due to expansion of the extracellular fluid volume) and hyperchloremic metabolic acidosis in this group of patients. This constellation of findings led to the suspicion of the possibility that their basis might be type II hypoaldosteronism. To test this hypothesis, 12 patients with hyperkalemia (plasma K+, 5.1 ± 0.2 mmol/ L at the time of study) while receiving cyclosporine were studied. Patients who had diabetes mellitus, those receiving drugs known to cause hyperkalemia (e.g., β blockers, angiotensin-converting enzyme inhibitors, K+-sparing diuretics), or those with a serum creatinine >200 μmol/L were excluded. The renal response to hyperkalemia was inappropriate because the transtubular K+ concentration gradient (TTKG) was only 4.3 ± 0.4 compared with a TTKG of 13 ± 1, 2 h after 50 mmol of KCI was given to normal subjects. The TTKG, after administration of 200 μg of fludrocortisone, was still very low (5.6 ± 0.6) in the patients compared with that of controls (12 ± 1). After administration of 250 to 500 mg of acetazolamide to increase the delivery of bicarbonate to the distal nephron, the TTKG rose significantly to 11 ± 1 in patients on cyclosporine, compared with 17 ± 1 in the controls. The rise in the rate of excretion of K+ and in the TTKG that occurred when sodium was delivered distally with bicarbonate suggests that the inappropriate renal response to hyperkalemia and the tubular insensitivity to mineralocorticoids may be due in part to an inability to generate a favorable electrical chemical gradient in the cortical distal nephron in the absence of bicarbonaturia or to a direct effect of bicarbonaturia on the apical membrane K+ channels.