THE HYPERFILTRATION HYPOTHESIS IN HUMAN RENAL-TRANSPLANTATION

The hyperfiltration hypothesis postulates that kidneys with reduced re nal mass will progress toward failure due to hypertrophy of the remain ing nephron to meet the excess load, eventually leading to nephron exh austion. Five conditions in which hyperfiltration might be suspected w ere studied in human kidney transplantation: (1) small kidneys from do nors aged 4 to 6; (2) transplants into large recipients (over 100 kg); (3) grafts from females to males compared with males to females; (4) kidneys that experience rejection episodes; and (5) cadaveric grafts c ompared with living-unrelated donor grafts. In all 5 instances, the re quirement for dialysis and discharge serum creatinine level were both high-and, correspondingly, the 1- and 3-year graft survival rates were lower than the controls. The discharge SCr was the best indicator of 1-3-year graft survival and may serve to measure the ''fit'' of the ki dney to the recipient-for even in patients requiring no dialysis graft survival was related to the discharge SCr levels. One consequence of this hypothesis is that many late graft losses currently attributed to rejections may, in fact, be hyperfiltration failures. As evidence, a progressively higher incidence of reported late rejections was noted e ven in patients who had been rejection-free at the time of discharge i f they had higher discharge SCr values. We conclude that the 5 conditi ons under which hyperfiltration damage might be suspected had increase d failure rates. Such failures are almost never reported as ''due to h yperfiltration'' and are probably recorded as rejections.