306 Several antigen dependent and non-antigen dependent factors operating before or early following renal transplantation have been shown to affect long-term graft survival. However it has not been determined whether these factors simply lower the Ccr early following transplantation or whether they affect the rate of loss of Ccr thereafter. In addition to information on pretransplant and early post-transplant variables and patient and graft outcomes, UNOS collects information on serum creatinine (Scr) levels at discharge, 6 months, and yearly post transplant. 238,586 individual serum creatinines obtained at 6 months or later were available in 42,250 patients from the 1997 UNOS Center Specific Report renal database for whom a 6-month and at least one subsequent Scr, and data to permit calculation of a Cockcroft-Gault estimate of Ccr, were available. Analysis of the data showed that the course of Ccr over time was approximately linear. We examined the impact of pre and early post transplant covariates on the 6-month Ccr (intercept) and on the subsequent slope. The average Ccr at 6 months was 59 ± 21 ml/min, and the average slope of Ccr was −0.19 ± 1.0 ml/min/month. There was a very weak correlation between estimated 6-month Ccr and the subsequent slope (r2=0.05). A lower Ccr at 6 months did not predict a more rapid subsequent loss of Ccr. Some variables affected both the 6-month Ccr and the subsequent slope, e.g., recipient race, total HLA mismatches, and requirement for dialysis in the first week. Increased recipient age lowered the intercept but also reduced the loss of Ccr over time. Donor age <30 was associated with both higher 6-month Ccr and less loss of Ccr over time, suggesting a greater capacity for renal growth in the recipient. Other variables affected only the intercept and not the slope of Ccr, e.g., live vs. cadaveric donor and cold ischemia time. Most surprising was that acute cellular rejection within the first six months affected only the six month Ccr (no rejection: 61 ml/min vs. rejection 53 ml/min, p < 0.001) but did not affect the subsequent rate of loss of Ccr at all. We conclude that changes in renal function following renal transplantation, as in renal disease in native kidneys, can be modeled by a linear slope. Premature graft failure after 6 months can occur either because of a lower starting point at 6 months or more rapid loss of function thereafter. This type of analysis may clarify the basis for premature graft loss and suggest new approaches to therapy. For example, with early acute rejection, perhaps more attention should be paid to reduction of fibrosis from the acute injury than to increased immunosuppression to prevent subsequent loss of function.
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Hunsicker et al. (1999) studied this question.