Abstract
Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. The hallmarks of progressive CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs are small, regulatory RNAs involved in many immunological processes. In particular, microRNA-21-5p (miR-21) is considered to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to assess urinary miR-21 expression levels in the kidney transplant recipients and determine their application in the evaluation of IFTA and kidney allograft function. The expression levels of miR-21 were quantified in the urine of 31 kidney transplant recipients with biopsy-assessed IFTA (IFTA 0 + I: n = 17; IFTA II + III: n = 14) by real-time quantitative PCR. Urine samples were collected at the time of protocolar biopsies performed 1 or 2 years after kidney transplantation. MicroRNA-191-5p was used as reference gene. MiR-21 was significantly up-regulated in IFTA II + III group compared to IFTA 0 + I group (p = 0.003). MiR-21 correlated significantly with serum concentration of creatinine (r = 0.52, p = 0.003) and eGFR (r = −0.45; p = 0.01). ROC analysis determined the diagnostic value of miR-21 with an area under curve (AUC) of 0.80 (p = 0.0002), sensitivity of 0.86 and specificity of 0.71. miR-21 is associated with renal allograft dysfunction and IFTA. Therefore, it could be considered as a potential diagnostic, non-invasive biomarker for monitoring renal graft function.
Highlights
Kidney transplantation (KTx) is currently the treatment of choice for patients with end-stage renal disease (ESRD)
Thirty-one kidney transplant recipients from our transplant center were included in the study
There was no statistical difference between the groups regarding age at biopsy, sex, body mass index, whether it was their first transplantation, cold and warm ischemia times, incidence of delayed graft function, time of biopsy after KTx, human leukocyte antigen (HLA) mismatches, immunosuppressive therapy and blood concentration of tacrolimus at the time of biopsy
Summary
Kidney transplantation (KTx) is currently the treatment of choice for patients with end-stage renal disease (ESRD). Within the last few decades, short graft survival has significantly improved due to modern immunosuppressive agents, advances in surgical techniques, organ preservation and postoperative care Despite these contributions, similar improvement in long-term outcomes was not observed [1]. Chronic renal allograft dysfunction (CAD) is one of the leading causes of long-term graft survival [2]. It is clinically asymptomatic and begins after the first transplantation year, resulting in continuous decline in allograft function [3]. Detection of this process is crucial as persistent dysfunction without appropriate intervention may lead to irreversible damage to the allograft and, eventually, allograft loss [4]. IFTA could be classified as mild (grade I, 50%) according to the Banff grading system [6]
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