An immunocytochemical study of H + ATPase in kidney transplant rejection

Abstract

Kidney transplant rejection may be accompanied by defective urinary acidification. Its pathogenesis is unknown. There are shared histologic features between kidney transplant rejection and the distal renal tubular acidosis (RTA) of Sjögren syndrome, which led us to hypothesize that deficient collecting duct H + adenosine triphosphatase (ATPase) expression—which is lacking in the RTA of Sjögren syndrome—may cause the RTA of kidney transplant rejection. Six kidney transplant recipients with biopsy evidence for rejection and two control subjects were studied physiologically and by immunohistochemistry. We found defective urinary acidification in all 6 kidney transplant patients. Ammonium excretion was diminished in relation to the degree of azotemia. There was an abnormal response to furosemide in all 6, suggesting distal tubular dysfunction. Distal H + ATPase staining was reduced in relation to the degree of azotemia, although it was not totally absent even in the worst case. This was paralleled by the urinary PCO 2 response. Both control subjects had good urine PCO 2 and H + ATPase staining and adequate urine pH response to furosemide. They had reduced urinary ammonium (NH 4) concentrations in relation to modest azotemia. We conclude that kidney transplant rejection may be accompanied by defective urinary acidification, which is not primarily due to a lack of H + ATPase. The RTA of kidney transplant rejection appears to result from defective ammonium excretion, generalized distal tubular malfunction, and—in severe cases—from a reduction in distal nephron H + ATPase expression.