MicroRNAs are key regulators of the normal kidney function and development, and altered in
acute kidney injury (AKI). However, there is a lack of studies comparing serum and urine
miRNA expression in toxic AKI in humans. We aimed to compare the global signature of urinary and serum
microRNAs, with and without kidney injury, after human
oxalic acid poisoning. We profiled urinary
microRNAs in patients who ingested
oxalic acid and developed no injury (No AKI n = 3), moderate injury (AKIN2 n = 3) or severe injury (AKIN3 n = 3) and healthy controls (n = 3). We validated a signature of 30 urinary
microRNAs identified in the discovery profiling, in a second cohort of individuals exposed to
oxalic acid (No AKI n = 15, AKIN2 n=11 & AKIN3 n= 18) and healthy controls (n=-27) and we compared the results with previously published serum data. Global profiling in toxic AKI patients showed a higher expression of urinary
microRNAs and lower expression of serum
microRNAs. Most urine
microRNA in the validation cohort were significantly upregulated (25/30, fold change >2.8 and p < 0.05) in AKIN2/3 patients compared to No AKI. Four urinary
microRNAs (miR-191, miR-19b, miR-20a and miR-30b) had good diagnostic performance (AUC greater than 0.8) to predict AKIN2/3 between 4-8 hours post ingestion.
Poisoning irrespective of AKI led to significantly lower expression of many
microRNAs in serum but relatively few changes in urinary
miRNA expression. In conclusion, urinary
microRNA signature provides a stronger measure of AKI in
oxalic acid poisoning compared to serum
microRNA. Kidney injury has the greatest impact on urinary
microRNA, while
poisoning itself was better reflected in serum
miRNA. Plasma and urinary
microRNAs signatures provide complementary information in toxic kidney injury.