Abstract

Abstract Background and Aims The prevalence of end-stage renal disease (ESRD) has increased ten times higher in the past twenty years, where renal replacement therapy (dialysis or kidney transplantation (KTx)) is the sole life-saving treatment. KTx is the preferred option as it is associated with improved survival and quality of life as well. Delayed graft function (DGF) is one of the main problems affecting long-term kidney survival. Brain-derived neurotrophic factor (BDNF) signalling pathways play pivotal role in mitigating cerebral ischemia/reperfusion injury (IRI), however the relation of BDNF and IRI in KTx is unknown. The aim of our human clinical study was to explore the relationship between serum BDNF concentration, BDNF gene polymorphism and renal graft function after KTx. Method Study characteristics: We enrolled 59 ESRD patients with average age of 54.8±12 years who received KTx. Proportion of male patients was 57%. Average cold ischemic time was 927±310 min, warm ischemic time was 54.5±39 min. DGF occurred in 5 cases. Baseline triple immunosuppression therapy consisted of tacrolimus, mycophenolate or everolimus, and prednisolone. Until now, 44 patients completed the 2 years follow-up. For a comparable control group, we collected blood samples from 79 healthy volunteers with average age of 53.9±16 years and with male gender proportion of 52%. Serum BDNF, creatinine, blood urea nitrogen, haemoglobin, blood glucose level and thrombocyte numbers were measured before KTx and 1 week, 1-, 3-, 6 months, and 1-, 2 years after transplantation, as well as in controls. GFR was estimated based on the CKD-EPI formula. BDNF Val66Met polymorphism was determined by PCR-RFLP. Results There was no difference in genotype or allele distribution between any of the groups, and no correlation could be observed between serum BDNF and different genotypes either. Serum BDNF level was lower in ESRD patients than healthy controls (p=0.03). There was a weak correlation and marginal significance (p=0.056) between eGFR and serum BDNF level in controls, while in KTx recipients this correlation reached higher significance (p=0.01). Above median BDNF values at 1 month after KTx were predictive for better graft function during the 2 observed years. Conclusion Our preliminary human study proposes that BDNF could be a novel biomarker of posttransplant graft function, however further clinical studies with significantly larger population are definitely needed to confirm these results.

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