Hyperfiltration, creatinine clearance and chronic graft loss

Chronic graft loss (CGL) may be caused by immunological- or hyperfiltration-mediated tissue destruction. If the hyperfiltration theory is correct, grafts from female donors given to heavy recipients, and having a relatively poor initial function, should suffer an accelerated rate of loss of function. 590 renal transplantations surviving more than 1 yr, including 171 cases of (CGL), were reviewed to identify causes of CGL. No overall influence of recipient or donor sex was found, but female donation resulted in lower acute graft loss and higher CGL. Warm ischemia affected CGL marginally, but cold ischemia < 12 h (excluding living donors) reduced CGL (35 vs. 53% at 10 yr, p < 0.05) and delayed function increased CGL (38% vs. 56% p < 0.001). Patients with a high urea production had high CGL (43% vs. 77%, p < 0.02). No overall effect of recipient weight was found; however 7 patients weighing > 90 kg all had CGL within 10 yr. Creatinine clearance was increasingly correlated to recipient weight (r = 0.23 at 1 yr, 0.38 at 10 yr, p < 0.001). For all years, change in creatinine clearance correlated with change in weight (p < 0.001). The most important factor predicting CGL was creatinine clearance, (> 80 ml/min: 6%, at 10 yr; 20-40 ml/min 53%). However, at any level of creatinine clearance, patients with late CGL had a slower loss of renal function. Rate of change of renal function was proportional to creatinine clearance, but only for grafts surviving > 6 yr. Creatinine clearance rose between 3 mths and 2 yr; this rise indicated a good prognosis, was related to recipient weight and weight increase, and was reduced in older donors and cyclosporine treated patients. For patients with low clearance ( < 60 ml/min), the increased CGL seen in patients with previous rejection episodes could be explained by their consequent lower clearance, but above this level, rejection episodes had an independent deleterious effect. These findings are compatible with hyperfiltration being the major cause of CGL after 6 yr. Before this immunological factors dominate. Good quality grafts respond to the increased protein load of heavy recipients with an increased GFR. Thus at any time, graft GFR is a function of protein-induced hyperfiltration, immunological graft destruction and hyperfiltration-mediated damage. Hyperfiltration-mediated renal damage is not a problem if the creatinine clearance is greater than 60 ml/min.