HYPERFILTRATION, CREATININE CLEARANCE AND CHRONIC GRAFT LOSS

Chronic graft loss (CGL) may be caused by immunological- or hyperfiltr ation-mediated tissue destruction. If the hyperfiltration theory is co rrect, 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 fe male 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 effec t of recipient weight was found; however 7 patients weighing > 90 kg a ll had CGL within 10 yr. Creatinine clearance was increasingly correla ted 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 i n weight (p < 0.001). The most important factor predicting CGL was cre atinine clearance, (> 80 ml/min: 6% at 10 yr; 20-40 ml/min 53%). Howev er, at any level of creatinine clearance, patients with late CGL had a slower loss of renal function. Rate of change of renal function was p roportional to creatinine clearance, but only for grafts surviving > 6 yr. Creatinine clearance rose between 3 mths and 2 yr; this rise indi cated a good prognosis, was related to recipient weight and weight inc rease, and was reduced in older donors and cyclosporine treated patien ts. For patients with low clearance (< 60 ml/min), the increased CGL s een in patients with previous rejection episodes could be explained by their consequent lower clearance, but above this level, rejection epi sodes had an independent deleterious effect. These findings are compat ible with hyperfiltration being the major cause of CGL after 6 yr. Bef ore this immunological factors dominate. Good quality grafts respond t o the increased protein load of heavy recipients with an increased GFR . Thus at any time, graft GFR is a function of protein-induced hyperfi ltration, 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.