The effect of kidney transplantation on distal tubular vacuolar H+-ATPase

The presence of vacuolar (v)H+-ATPase in distal tubule alpha-intercalated cells is essential for hydrogen excretion and maintenance of acid-base homeostasis. Loss of vH+-ATPase after kidney transplantation could cause posttransplant distal renal tubular acidosis (dRTA).

Immunostaining of the kidney specific vH+-ATPase of cortical collecting duct cells (CCT) was performed in 37 kidney biopsies taken immediately prior to transplantation and after engraftment (median [range]: 10 [1-181] months). Apical or intracytoplasmatic staining intensity was classified as grade 0 (absent), grade 1 (weak), or grade 2 (strong), and positive cells expressed as percentage of all CCT cells. In addition, kidney biopsies were scored for damage by the Banff schema. Serum and urinary pH, anion gap, and serum potassium were obtained for the diagnoses of dRTA.

Fourteen transplant recipients had dRTA type I, 5 had rate-limited RTA, six had type IV dRTA, and 12 had no RTA. In pretransplant biopsies, 40% [3-77%] of CCT cells were positive for vH+-ATPase but only 17% [0-39%] after transplantation (P<0.0001). The loss of vH+-ATPase expression was similar in patients with dRTA type I (-21%), type IV (-25%), rate limited RTA (-21%), or no RTA (-29%). The decrease affected predominantly the apical proton pump expression. The individual loss of vH+-ATPase expression was not related to the time elapsed since transplantation, immunosuppressive drugs, acute transplant rejection, or tubulointerstitial changes.

Kidney transplantation leads to a general decrease of distal tubular vH+-ATPase expression. Loss of proton pump activity occurs unrelated to immunosuppressive therapy or transplant related histologic changes.