DECREASED NEPHRON MASS (NM) IS NOT ASSOCIATED WITH WORSENED RENAL SURVIVAL, FUNCTION OR PROTEINURIA IN LIVING DONOR (LD) RENAL TRANSPLANTS: A MODEL FOR FUTURE RENAL TRANSPLANTATION (RT)

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20 There is controversy whether reduced NM superimposed on other renal insults, acute rejection (AR), cyclosporine (CsA) and ischemia leads to chronic graft loss. Living donor (LD) transplantation is a useful model to look at whether NM will be clinically relevant in the future of as new immunosuppresants will result in less AR and less CsA; low ATN rates, as we have reported, are already achieveable. Our model shows the effect of reduced NM when AR and CsA is mimimized. As a comparison, LD recipients (LDR) received significantly less CsA at 1 yr, 388 mg/d ± 175 vs. 436± 153 (p<0.05) in cadaver recipients (CR) transplanted in the same time. 35% of LDR experienced an AR episode compared to 43% of CR (p<0.05). We determined the body mass index (BMI) of 200 LD and recipients (R) undergoing LTx at our center between 1/1/90 and 12/31/96. Donor source (%) was sib-48, child-28, parent-16, unrelated-9. The BMI was used as a marker of NM and the BMI ratio of the R to the LD determined. R with >20% BMI of LD were classified as nephron underdosed (U), n=36; R<20% of LD BMI nephron overdosed (O), n=41; and those in between, matched (M), n=123. We retrospectively reviewed serum creatinine (Cr), the most recent 24 hr urine protein and determined graft survival (GS). Reports of renal biopsies obtained for graft dysfunction were reviewed to assess for presence of focal semental sclerosis (FGS) and interstitial fibrosis (IF). Results: Overall death censored GS was similar, 83, 82 and 85% (p=not significant, NS) in O, M and U respectively. Renal function assessed by Cr was not different between groups at 2 weeks, 1 or 3 yrs. At 3 yrs, Cr was 1.92 ±0.73, 1.79±0.65, 1.86 ±0.58 mg/dl (p=NS) and there was no increase in proteinuria - 1.1 ±1.9, 1.0 ±1.6, and 1.7 ±2.6 g/24 hrs(p=NS) in O, M and U respectively. There was likewise no increase in FGS or IF in the U group. Conclusion: In our model which may better represent the future of RT-namely, reduced incidence of AR and less nephrotoxic immunosuppressives, nephron underdosing had no demonstrable negative effects in terms of graft survival, function, or development of proteinuria. Similarly, increase NM did not appear to be beneficial. Thus, attempts to match NM in the future may not be clinically relevant or beneficial.