KIDNEY - CHRONIC GRAFT INJURY

J. Pazik¹, M. O?dak², M. D?browski², Z. Lewandowski³, J. Pazik⁴, E. Sitarek⁵, T. Grochowiecki⁶, A. Chmura⁷, R. P?oski⁸, J. Malejczyk², M. Durlik^5
1Dept Of Transplantation Medicine And Nephrology, Warsaw Medical School, Warsaw/POLAND, ²Histology And Embryology, Medical University of Warsaw, Warsaw/POLAND, ³Dept Of Epidemiology, Medical University, Warsaw/POLAND, ⁴Department Of Transplantation Medicine And Nephrology, Medical University, Warsaw/POLAND, ⁵Dept Of Transplantation Medicine And Nephrology, Medical University of Warsaw, Warsaw/POLAND, ⁶Dept Of General, Vascular And Transplantation Surgery, Medical University of Warsaw, Warsaw/POLAND, ⁷Dept Of General And Transplantation Surgery, Medical University of Warsaw, Warsaw/POLAND, ⁸Forensic Medicine, Medical University of Warsaw, Warsaw/POLAND

Body: Introduction: UDP-glucuronosyltransferases (UGTs) are group of enzymes involved in the detoxification and excretion of many xeno- and endobiotics. In kidney allograft recipients UGT1A9 polymorphisms were shown to influence mycophenolate mophetil exposition. Study aim: to evaluate the association of the key clinical features of kidney post-transplant course and UGT1A9 SNPs 2152C>T, 275 T>A, 98T>C, known to influence enzyme expression and mycophenolic acid exposition. Patients and methods: In 106 kidney allograft recipients remaining on immunosuppressive regimens based on mycophenolate mophetil and either cyclosporine A or tacrolimus, DNA was extracted from blood samples by a standard salting out method. UGT1A9 2152C>T, 275 T>A, 98T>C genetic variants were genotyped by specific PCR sequence amplification followed by restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between listed SNPs and kidney allograft function – expressed as GFR and/or proteinuria existence, acute rejection frequency and severity, infectious complications, PTDM occurrence, WBC, RBC and platelet counts in preselected time-points were evaluated. Statistical analysis was performed using GLM Procedure of SAS System and Fisher’s Exact Test. Results: In individuals carrying allele C of UGT1A9 98T>C SNP graft function (expressed as eGFRC&G) 1 month after engraftment was 43.7 vs 54.1ml/min/1.73m² in non-carriers (p=ns), while at 3 month 42.4 vs 63.5 (p=0.009), at 6 months 66.9 vs 48.4 (p=0.029), and at 12 months 68.0 vs 43.7 (p=0.025 ). The differences in filtration rates increased with time, formed a plateau in variant C carriers and increased in non-carriers (p<0.0338). UGT1A9 98T>C SNP allel C presence enhanced risk of proteinuria at 1 months (50% vs 15,4% ; p=0.065) and at 2 month (50 vs 10 %; p=0.026) after engraftment. Conclusions: UDP gluculonylotransferase polimorphisms are intensely evaluated as potentially influencing mycophenolic acid metabolism, and indirectly it’s effectiveness in acute rejection prophylaxis. Our data show that polymorphisms diminishing UGT1A9 activity influence kidney allograft function, probably in more complex and until yet undefined mechanism.

Disclosure: All authors have declared no conflicts of interest.