Protective role of NHE-3 inhibition in rat renal transplantation undergoing acute rejection.

Acute rejection in renal transplantation disturbs solute and volume maintenance in humans accompanied by delayed graft function and poor prognosis. We recently reported that decreased expression and function of Na+/H+ exchanger type 3 (NHE-3) in proximal tubules and epithelial Na+ channels and aquaporin 2 in collecting ducts are major mechanisms involved in Na+ and water imbalances shortly after transplantation in rat undergoing acute rejection. We performed kidney transplantations in rats with bilaterally nephrectomized recipients with acute rejection and, in addition, systemically administered a specific inhibitor of NHE-3 (NHE-I). NHE inhibition in acute renal failure was shown to improve tubular function and recovery. The aim of this therapy was to reduce energy consumption of the graft and preserve NHE-3 function. Imbalances in electrolyte excretion declined in NHE-I-treated animals and NHE-3 activity was preserved. Observed NHE-I-dependent changes in electrolyte excretion, polyuria, and reduced protein reabsorption in the acute postoperative phase are predictors of favorable graft outcome in humans.