The hyperfiltration hypothesis in human renal transplantation

The hyperfiltration hypothesis postulates that kidneys with reduced renal mass will progress toward failure due to hypertrophy of the remaining nephron to meet the excess load, eventually leading to nephron exhaustion. Five conditions in which hyperfiltration might be suspected were studied in human kidney transplantation: (1) small kidneys from donors 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 compared with living-unrelated donor grafts. In all 5 instances, the requirement 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 kidney 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 even in patients who had been rejection-free at the time of discharge if they had higher discharge SCr values. We conclude that the 5 conditions under which hyperfiltration damage might be suspected had increased failure rates. Such failures are almost never reported as "due to hyperfiltration" and are probably recorded as rejections.