Circular RNAs in Urine of Kidney Transplant Patients with Acute T Cell-Mediated Allograft Rejection

BACKGROUND Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They are detectable in the blood of patients with acute kidney injury. We tested whether circRNAs were present in urine and could serve as new predictors of outcome in renal transplant patients with acute rejection. METHODS A global circRNA expression analysis using RNA from urine of patients with acute T cell-mediated renal allograft rejection and control transplant patients was performed. Dysregulated circRNAs were confirmed in a cohort of 62 patients with acute rejection, 10 patients after successful antirejection therapy, 18 control transplant patients without rejection, and 13 stable transplant patients with urinary tract infection. RESULTS A global screen revealed several circRNAs to be altered in urine of patients with acute rejection. Concentrations of 2 circRNAs including hsa_circ_0001334 and hsa_circ_0071475 were significantly increased. These were validated in the whole cohort of patients. hsa_circ_0001334 was upregulated in patients with acute rejection compared with controls. Concentrations of hsa_circ_0001334 normalized in patients with acute rejection following successful antirejection therapy. hsa_circ_0001334 was associated with higher decline in glomerular filtration rate 1 year after transplantation. CONCLUSIONS CircRNA concentrations are significantly dysregulated in patients with acute rejection at subclinical time points. Urinary hsa_circ_0001334 is a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.