The outcome of living related (LD) HLA-identical kidney transplant (tx) was excellent prior to the availability of calcineurin inhibitors (CNIs). Given the nephrotoxicity of CNIs, we asked whether the addition of CNIs improved outcomes for these recipients. We studied patient and graft survival of HLA identical LD transplant recipients for 3 different immunosuppression eras: ERA 1 (up to 1984): anti-lymphocyte globulin (ALG) induction and maintenance immunosuppression with prednisone (P) and azathioprine (AZA) (n=114); ERA 2 (1984-1999): CNIs added; evolution from ALG to Thymoglobulin; evolution from AZA to mycophenolate (MMF) (n=262); ERA 3 (1999-2011): rapid discontinuation of P (Thymoglobulin induction and CNI and MMF maintenance) in recipients having 1st or 2nd tx and not on P at the time of tx (n=77). Demographics that differed by era: a) ↑ tx recipient age (p<.0001) and ↑donor age (p<.0001) with each advancing era; and b) fewer Caucasian donors (p=0.02) and recipients (p=0.003) in ERA 3.
Results: Actuarial patient and graft survival rates were not significantly different between eras.
|ERA 1 (Pre-CNI) N=114||ERA 2 (CNI+steroids) N=262||ERA 3 (Steroid free CNI) N=77|
|PATIENT SURVIVAL (p 0.6)|
|1 yr||96% (n=110)||98% (n=255)||96% (n=71)|
|5 yr||89% (n=100)||95% (n=243)||93% (n=46)|
|10 yr||82% (n=92)||84% (n=214)||Insufficient n|
|DEATH CENSORED GRAFT SURVIVAL (p 0.8)|
|1 yr||98% (n=108)||99% (n=252)||100% (n=71%)|
|5 yr||96% (n=98)||93% (n=228)||94% (n=43)|
|10 yr||86% (n=83)||88% (n=197)||Insufficient n|
There were no significant differences in the cause of death by era (p 0.5); but there were numerically higher death rates from infection with each advancing era; 3/64 (5%) in ERA 1, 14/90(16%) in ERA 2, and 2/10 (20%) in ERA 3. There were more cardio-vascular death in ERA 1 (22/64, 34%) vs. ERA 2 (16/90, 18%, p=0.01). There were no group differences in graft loss from acute rejection. The incidence of graft loss from chronic rejection/ chronic allograft nephropathy was greater in the CNI eras (p=0.02). There were no significant differences in the 1/creatinine slopes between eras for the 1st yr (p=0.6), 2nd yr (p=0.9), or >2 yrs post-tx(p=0.4). When antibody induction was used, we found no benefit of CNIs for HLA identical LD recipients. Whether these patients could tolerate rapid discontinuation of prednisone without CNIs may be a question worthy of testing.
To cite this abstract in AMA style:Verghese P, Dunn T, Chinnakotla S, Gillingham K, Matas A, Mauer M. Calcineurin Inhibitors in HLA Identical Living Related Donor Kidney Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/calcineurin-inhibitors-in-hla-identical-living-related-donor-kidney-transplantation/. Accessed May 7, 2021.
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