Dataset Information

PIRCHE-II Is Related to Graft Failure after Kidney Transplantation.

ABSTRACT: Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10-1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival.

SUBMITTER: Geneugelijk K

PROVIDER: S-EPMC5844930 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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PIRCHE-II Is Related to Graft Failure after Kidney Transplantation.

Geneugelijk Kirsten K Niemann Matthias M Drylewicz Julia J van Zuilen Arjan D AD Joosten Irma I Allebes Wil A WA van der Meer Arnold A Hilbrands Luuk B LB Baas Marije C MC Hack C Erik CE van Reekum Franka E FE Verhaar Marianne C MC Kamburova Elena G EG Bots Michiel L ML Seelen Marc A J MAJ Sanders Jan Stephan JS Hepkema Bouke G BG Lambeck Annechien J AJ Bungener Laura B LB Roozendaal Caroline C Tilanus Marcel G J MGJ Vanderlocht Joris J Voorter Christien E CE Wieten Lotte L van Duijnhoven Elly M EM Gelens Mariëlle M Christiaans Maarten H L MHL van Ittersum Frans J FJ Nurmohamed Azam A Lardy Junior N M JNM Swelsen Wendy W van der Pant Karlijn A KA van der Weerd Neelke C NC Ten Berge Ineke J M IJM Bemelman Fréderike J FJ Hoitsma Andries A van der Boog Paul J M PJM de Fijter Johan W JW Betjes Michiel G H MGH Heidt Sebastiaan S Roelen Dave L DL Claas Frans H FH Otten Henny G HG Spierings Eric E

Frontiers in immunology 20180305

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in <i>de novo</i> donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluat ...[more]

PMID: 29556227

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Project description:BackgroundLittle is known about the time-varying determinants of kidney graft failure in children.MethodsWe performed a retrospective study of primary pediatric kidney transplant recipients (younger than 18 years) from the Eurotransplant registry (1990-2020). Piece-wise exponential additive mixed models were applied to analyze time-varying recipient, donor, and transplant risk factors. Primary outcome was death-censored graft failure.ResultsWe report on 4528 kidney transplantations, of which 68% with deceased and 32% with living donor. One thousand six hundred and thirty-eight recipients experienced graft failure, and 168 died with a functioning graft. Between 2011 and 2020, the 5-year graft failure risk was 10% for deceased donor and 4% for living donor kidney transplant recipients. Risk of graft failure decreased five-fold from 1990 to 2020. The association between living donor transplantation and the lower risk of graft failure was strongest in the first month post-transplant (adjusted hazard ratio, 0.58; 95% confidence interval, 0.46 to 0.73) and remained statistically significant until 12 years post-transplant. Risk factors for graft failure in the first 2 years were deceased donor younger than 12 years or older than 46 years, potentially recurrent kidney disease, and panel-reactive antibody >0%. Other determinants of graft failure included dialysis before transplantation (until 5 years post-transplant), human leukocyte antigen mismatch 2-4 (0-15 years post-transplant), human leukocyte antigen mismatch 5-6 (2-12 years post-transplant), and hemodialysis (8-14 years post-transplant). Recipients older than 11 years at transplantation had a higher risk of graft failure 1-8 years post-transplant compared with other age groups, whereas young recipients had a lower risk throughout follow-up. Analysis of the combined effect of post-transplant time and recipient age showed a higher rate of graft failure during the first 5 years post-transplant in adolescents compared with young transplant recipients. In contrast to deceased donor younger than 12 years, deceased donor older than 46 years was consistently associated with a higher graft failure risk.ConclusionsWe report a long-term inverse association between living donor kidney transplantation and the risk of graft failure. The determinants of graft failure varied with time. There was a significant cumulative effect of adolescence and time post-transplant. The ideal donor age window was dependent on time post-transplant.

Project description:Background and objectivesHypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up.Design, setting, participants, & measurementsWe performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center. We used a large real-life dataset containing 28,178 phosphate measurements (median of 27; first to third quartiles, 23-34) serial measurements per patient) and selected the lowest intraindividual phosphate level during the first year after transplantation. The primary outcomes were all-cause mortality, cardiovascular mortality, and death-censored graft failure.ResultsThe median (interquartile range) intraindividual lowest phosphate level was 1.58 (1.30-1.95) mg/dl, and it was reached at 33 (21-51) days post-transplant. eGFR was the main correlate of the lowest serum phosphate level (model R2 =0.32). During 9 (5-12) years of follow-up, 181 (19%) patients developed graft failure, and 295 (35%) patients died, of which 94 (32%) deaths were due to cardiovascular disease. In multivariable Cox regression analysis, more severe hypophosphatemia was associated with a lower risk of death-censored graft failure (fully adjusted hazard ratio, 0.61; 95% confidence interval, 0.43 to 0.88 per 1 mg/dl lower serum phosphate) and cardiovascular mortality (fully adjusted hazard ratio, 0.37; 95% confidence interval, 0.22 to 0.62) but not noncardiovascular mortality (fully adjusted hazard ratio, 1.33; 95% confidence interval, 0.9 to 1.96) or all-cause mortality (fully adjusted hazard ratio, 1.15; 95% confidence interval, 0.81 to 1.61).ConclusionsPost-transplant hypophosphatemia develops early after transplantation. These data connect post-transplant hypophosphatemia with favorable long-term graft and patient outcomes.

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PIRCHE-II Is Related to Graft Failure after Kidney Transplantation.

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PIRCHE-II Is Related to Graft Failure after Kidney Transplantation.

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