TY - JOUR
T1 - The impact of transforming growth factor-β1 gene polymorphism on end-stage renal failure after heart transplantation
AU - van de Wetering, Jacqueline
AU - Weimar, CHE
AU - Balk, Aggie
AU - Roodnat, J.I.
AU - Holweg, C
AU - Baan, Carla
AU - van Domburg, Ron
AU - Weimar, Willem
PY - 2006/12
Y1 - 2006/12
N2 - BACKGROUND. Nephrotoxicity is a major side effect of calcineurin inhibitors (CNI). Earlier we reported 8% of our heart transplant recipients reaching end-stage renal failure (ESRF). Now, with an extended follow up of 20 years, we re-evaluated the development of ESRF and studied its influence on survival and the impact of polymorphisms in codon 10 and 25 of the promoter region of transforming growth factor (TGF)-β on the risk of ESRF. METHODS. In all, 465 patients were transplanted between June 1984 and June 2005. All were on maintenance CNI treatment. Development of ESRF was studied in 402/465 (86.5%) patients surviving at least one year. Their median follow up was eight years, total observation time of 3,414 years. TGF-β polymorphisms in codon 10 (Leu to Pro) and codon 25 (Arg to Pro) were analyzed with real-time polymerase chain reaction in a cohort of 237 patients, with an observation time of 2,329 years. RESULTS. Ten-year survival of patients surviving at least one year was 58.5%. Seventy-three patients (18.2%) developed ESRF. Dialysis-free survival was 60% at 15 years. The relative risk for ESRF in Pro carriers was 2.9 (CI 1.5-5.8) compared to patients with the Leu/Leu genotype (P=0.002), while Pro carriers had a RR of 2.6 (CI 1.4-4.8) compared to the Arg/Arg genotype (P=0.002). Survival of patients with ESRF was 1.5 years (median). CONCLUSION. We found a highly significant association between TGF-β polymorphisms and CNI induced ESRF after heart transplantation (HTx). Pro carriers of either codon 10 or 25 had a 2.6 to 2.9 times increased risk of developing ESRF. As ESRF after HTx results in high mortality rates these patients should no longer receive CNI-based immunosuppression.
AB - BACKGROUND. Nephrotoxicity is a major side effect of calcineurin inhibitors (CNI). Earlier we reported 8% of our heart transplant recipients reaching end-stage renal failure (ESRF). Now, with an extended follow up of 20 years, we re-evaluated the development of ESRF and studied its influence on survival and the impact of polymorphisms in codon 10 and 25 of the promoter region of transforming growth factor (TGF)-β on the risk of ESRF. METHODS. In all, 465 patients were transplanted between June 1984 and June 2005. All were on maintenance CNI treatment. Development of ESRF was studied in 402/465 (86.5%) patients surviving at least one year. Their median follow up was eight years, total observation time of 3,414 years. TGF-β polymorphisms in codon 10 (Leu to Pro) and codon 25 (Arg to Pro) were analyzed with real-time polymerase chain reaction in a cohort of 237 patients, with an observation time of 2,329 years. RESULTS. Ten-year survival of patients surviving at least one year was 58.5%. Seventy-three patients (18.2%) developed ESRF. Dialysis-free survival was 60% at 15 years. The relative risk for ESRF in Pro carriers was 2.9 (CI 1.5-5.8) compared to patients with the Leu/Leu genotype (P=0.002), while Pro carriers had a RR of 2.6 (CI 1.4-4.8) compared to the Arg/Arg genotype (P=0.002). Survival of patients with ESRF was 1.5 years (median). CONCLUSION. We found a highly significant association between TGF-β polymorphisms and CNI induced ESRF after heart transplantation (HTx). Pro carriers of either codon 10 or 25 had a 2.6 to 2.9 times increased risk of developing ESRF. As ESRF after HTx results in high mortality rates these patients should no longer receive CNI-based immunosuppression.
UR - https://www.scopus.com/pages/publications/33845951304
U2 - 10.1097/01.tp.0000250360.78553.5e
DO - 10.1097/01.tp.0000250360.78553.5e
M3 - Article
C2 - 17198270
SN - 0041-1337
VL - 82
SP - 1744
EP - 1748
JO - Transplantation
JF - Transplantation
IS - 12
ER -