Electrolyte and Acid-base disturbances induced by clacineurin inhibitors

Abstract

Nephrotoxicity is the most common and clinically significant adverse effect of calcineurin inhibitors. Cyclosporine and tacrolimus nephrotoxicity is manifested by both acute azotemia and chronic progressive renal disease and tubular zdysfunction. An elevation in the plasma potassium concentration due to reduced efficiency of urinary potassium excretion is common in cyclosporine-treated patients; it may be severe and potentially life-threatening with concurrent administration of an angiotensin converting enzyme inhibitor, which diminishes aldosterone release. Tubular injury induced by cyclosporine can also impair acid excretion. This may be presented as a hyperchloremic metabolic acidosis associated with decreased aldosterone activity and suppression of ammonium excretion by hyperkalemia. Some patients treated with cyclosporine develop hypophosphatemia due to urinary phosphate wasting. Renal magnesium wasting is also common presumably due to drug effects on magnesium reabsorption. Hypomagnesemia has also been implicated as a contributor to the nephrotoxicity associated with cyclosporine. Both cyclosporine and tacrolimus are associated with hypercalciuria. Attention must be paid to drug dose, side effects, and drug interactions to minimize toxicity and maximize efficacy.

Keywords: Acidosis; Calcineurin inhibitors; Hypercalciuria; Hyperkalemia; Hypomagnesemia; Hypophosphatemia.

Fig. 1

Intercalated cells of collecting ducts. Collecting ducts have 2 types of intercalated cells: acid or hydrogen ion-secreting alpha-intercalated cell and bicarbonate-secreting beta-intercalated cell.

Fig. 2

Presumed mechanism of cyclosporine-induced metabolic acidosis. Cyclosporine inhibits polymerization of hensin protein, consequently acid-secreting cells will be less and then become at risk for mild normal anion gap metabolic acidosis.

Fig. 3

Chloride shunt theory and clacineurin inhibitors. Calcineurin inhibitors inhibit the luminal potassium channel and increase chloride reabsorption.