Underlying Causes and Risk Factors of Chronic Renal Allograft Dysfunction Among Renal Transplant Recipients

Objective: Dialysis or renal transplantation are the two treatment options for end-stage renal disease patients. Renal transplantation from an appropriate donor increases survival and quality of life compared to treatment with dialysis. Recent advances in immunosuppressive therapy have significantly improved the success in 1-year graft survival. However, the long-term graft survival remains the same. Therefore, we aimed to determine the underlying causes and risk factors of chronic allograft dysfunction in renal transplant recipients. Materials and Methods: From 2000 to 2012, all consecutive renal transplant recipients followed in our tertiary referral center who underwent renal biopsy due to an increase in serum creatinine level were enrolled. Etiologies of chronic allograft dysfunction were assessed according to pathologic results of renal biopsy specimens and laboratory findings. The immunological and non-immunological risk factors of chronic allograft dysfunction were screened and recorded retrospectively. Results: Eighty (80) renal transplant recipients with a mean age of 38±10 years were included in the study. Delayed graft function (p=0.007), history of acute rejection (p<0.001), positive panel reactive antibody (p=0.033) (Class I (p=0.013), Class II (p=0.006)), positive donor specific antibodies (p=0.001), number of recurrent acute rejections (p<0.001), number of human leukocyte antigens mismatches (p=0.051), cold ischemia time (p=0.001) were found to be risk factors for chronic allograft dysfunction. The donor specific antibodies positivity (p<0.001) and the panel reactive antibody positivity (Class I (p=0.003), Class II (p=0.001)) were significantly higher in patients with antibody mediated rejection than patients without antibody mediated rejection (p=0.002). Conclusion: Delayed graft function, presence and the number of acute rejections, increased cold ischemia time, panel reactive antibody positivity, donor specific antibodies positivity, and the number of human leukocyte antigens mismatches were risk factors for chronic allograft dysfunction.

Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival

Background and objectivesPanel reactive antibody informs the likelihood of finding an HLA-compatible donor for transplant candidates, but has historically been associated with acute rejection and allograft survival because testing methods could not exclude the presence of concomitant donor-specific antibodies. Despite new methods to exclude donor-specific antibodies, panel reactive antibody continues to be used to determine the choice of induction and maintenance immunosuppression. The study objective was to determine the clinical relevance of panel reactive antibody in the absence of donor-specific antibodies.Design, setting, participants, & measurementsRetrospective observational study of kidney allograft survival among 4058 zero HLA-A–, B-, DR-, and DQB1-mismatched transplant recipients without antibodies to donor kidney antigens encoded by these HLA gene loci.ResultsAmong 4058 first and repeat transplant recipients, patients with calculated panel reactive antibody (cPRA) 1%–97% were not at higher risk of transplant failure, compared with patients with cPRA of 0% (death censored graft loss: hazard ratio, 1.07; 95% confidence interval, 0.82 to 1.41). Patients with cPRA ≥98% had a higher risk of graft loss from any cause including death (hazard ratio, 1.39; 95% confidence interval, 1.08 to 1.79) and death censored allograft failure (hazard ratio, 1.78; 95% confidence interval, 1.27 to 2.49). In stratified analyses, the higher risk of graft loss among patients with cPRA ≥98% was only observed among repeat, but not first, transplant recipients. In subgroup analysis, there was no association between cPRA and graft loss among living related transplant recipients.ConclusionsCalculated panel reactive antibody is poorly associated with post-transplant immune reactivity to the allograft in the absence of donor-specific antibody.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3