THE VARIABLE NATURE OF CHRONIC DECLINES IN RENAL-ALLOGRAFT FUNCTION

Despite having important implications for the design of therapeutic trials, the clinical setting, time of onset, and rate of progression for chronic declines in renal allograft function have not been well characterized. In the present investigation, monthly estimates of glomerular filtration rate (E-GFR) were made using creatinine clearance and interim serum creatinine levels. There were 200 patients transplanted from 1978 to 1982 (precyclosporine) who survived at least 12 months with a functioning allograft. Of these, 25 had irreversible declines in E-GFR (greater than 30%) attributable to acute rejection, 50 had gradual, chronic declines in E-GFR, and 125 maintained stable function. Patients with chronic declines in E-GFR more often returned to dialysis (56%, P < 0.001) than those with irreversible, acute reductions (24%), or stable function (2%). Chronic declines in allograft function were modeled by one or two least-squares-fitted regression lines. In most cases, the onset was early, but in 26% chronic declines in E-GFR began 2.2 +/- 1.2 (mean +/- SD) years after transplantation. Among those with chronic declines in E-GFR, 20/50 (40%) had spontaneous improvements in the rate of progression after 2.7 +/- 1.1 years and survived 8.4 +/- 2.6 years with functioning grafts, while 30/50 (60%) continued to have progressive declines in E-GFR and survived 6.1 +/- 2.5 years (P < 0.01). Although chronic declines in E-GFR were evident 3.2 +/- 1.7 years before graft failure, routinely measured clinical and laboratory parameters from the early posttransplant period failed to predict patients who developed chronic declines in E-GFR. Altogether these data suggest that chronic declines in allograft function have an unpredictable onset and variable clinical course.