MICROSOMAL LIVER-FUNCTION DECLINES STEADILY AFTER KIDNEY GRAFTING - A 3 TO 5 YEAR FOLLOW-UP

We have previously shown that the functioning hepatocyte mass (galactose elimination capacity, GEC) and microsomal liver functions (non-renal clearances of unbound prednisolone and cyclosporin A) are impaired in renal allograft recipients (N = 28) one month and one year after successful transplantation. To assess the natural history of these hepatic functional derangements, we reinvestigated 21 patients with stable renal function three to five years following grafting. GEC remained with 6.07 +/- 0.86 mg/min x kg significantly (P < 0.001) below that in healthy controls (7.52 +/- 0.78 mg/min x kg), but did not significantly change during follow-up (5.93 +/- 0.96 and 6.26 +/- 0.94 mg/min x kg at 1 year and 1 month, respectively). In contrast, the non-renal clearance of unbound prednisolone declined steadily during follow-up averaging 4.98 +/- 0.71 ml/min x kg at three to five (compared to 5.83 +/- 1.51 and 6.80 +/- 1.73 ml/min x kg at one year and one month, respectively). These values were lower (P < 0.01) than those observed in healthy control subjects (7.56 +/- 1.59 ml/min x kg). The total body clearance of cyclosporin A decreased similarly with time averaging 4.5 +/- 1.2 ml/min x kg at three to five years (compared to 4.9 +/- 1.2 and 5.9 +/- 2.1 ml/min x kg at 1 year and 1 month, respectively). In conclusion: 1) the functioning hepatocyte mass and microsomal liver functions are markedly impaired in renal allograft recipients; 2) microsomal liver functions, but not the functioning hepatocyte mass, steadily decline with time during three to five years after transplantation, despite the absence of clinical and (routine) laboratory evidence of significant liver disease and excellent graft function.