Circulating human microRNA biomarkers of oxalic acid-induced acute kidney injury.

Oxalic acid-induced nephrotoxicity and acute kidney injury result from formation of calcium oxalate crystals. Oxalic acid-induced acute kidney injury is a significant problem in many parts of the world. Circulating biomarkers that can accurately and reproducibly detect acute kidney injury are highly desirable. We used a high sensitivity discovery platform to identify signature microRNAs to distinguish healthy individuals never exposed to oxalic acid (n = 4) from those who were exposed to oxalic acid but had no injury (NOAKI; n = 4), moderate injury (AKIN2; n = 4) or severe injury (AKIN3; n = 4). Longitudinal analyses identified 4-8 h post-ingestion as the best time to detect AKIN2/3. We validated a signature of 53 microRNAs identified in the discovery, in a second cohort of individuals exposed to oxalic acid (NOAKI = 11, AKIN2 = 8 and AKIN3 = 18) and healthy controls (n = 19). Thirteen microRNAs were significantly downregulated in acute kidney injury patients compared to NOAKI within 8-h post-ingestion. Five microRNAs (miR-20a, miR-92a, miR-93, miR-195, miR-451) had a highly significant correlation with normalized urinary albumin, serum creatinine at 24 h and creatinine clearance. Logistic regression of these microRNAs had AUC-ROC of 0.85 predicting AKIN2/3 and discriminated patients from healthy controls (AUC-ROC = 0.93). mRNA targets of these microRNAs identified oxidative stress pathways of nephrotoxicity in proximal tubule and glomeruli nephrotoxicity. In conclusion, the downregulation of multiple circulating microRNAs in patients correlated with the severity of oxalic acid-induced acute kidney injury. A set of microRNAs (miR-20a, miR-92a, miR-93, miR-195, miR-451) could be promising biomarkers for early detection of oxalic acid-induced acute kidney injury.