RESUMEN
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.
RESUMEN
INTRODUCTION: Early prognostic markers that identify highrisk kidney transplant recipients may lead to optimization of immunosuppressive therapy and improved longterm outcomes. OBJECTIVES: The aim of this study was to assess whether the measurement of urinary concentrations of CCL2 and CXCL10 chemokines can be a valuable noninvasive tool for identifying ongoing pathological processes in a kidney allograft. PATIENTS AND METHODS: The study included 40 patients who underwent a protocol biopsy within 1year post kidney transplant. The urinary concentrations of CCL2 and CXCL10 with reference to creatinine in urine were assayed in all patients. On the basis of biopsy results, a study group was selected (n = 25), including patients with a diagnosis of interstitial fibrosis and tubular atrophy grades II to III (n = 16), BK virus (BKV) nephropathy (n = 4), or mild inflammatory lesions fulfilling the criteria for mild rejection processes or borderline lesions (n = 11). Patients with normal biopsy results were included in a control group (n = 15). RESULTS: The ratio of CCL2 to creatinine (CCL2:Cr) was a significant independent predictor of BKV ephropathy (odds ratio, 1.1; 95% CI, 1.0-1.2; P = 0.04). The CXCL10:Cr ratio was not found to be an independent predictor of BKV nephropathy (odds ratio, 1.3; 95% CI, 0.99-1.71; P = 0.06). CONCLUSIONS: The CCL2:Cr and CXCL10:Cr ratios may predict BKV nephropathy. The diagnostic value of CCL2 and CXCL10 in BKV infection should be further evaluated.
