Urinary MicroRNA-30c-5p and MicroRNA-192-5p as potential biomarkers of ischemia–reperfusion-induced kidney injury

Abstract

Early detection of acute kidney injury is difficult due to lack of known biomarkers; previous studies have tried to identify new biomarkers for detecting acute kidney injury at an early stage. MicroRNA, a 21-23 nucleotide noncoding RNA molecule, has emerged as a desirable marker in the diagnosis and prognosis of various diseases. This study aims to identify the expression profile of microRNA in ischemia-reperfusion-induced kidney injury and determine the possibility of using the candidate microRNA as biomarker for the detection of I/R-induced kidney injury. Based on the established rat model of I/R-induced kidney injury, a microarray analysis of rat urine was performed at the beginning of operation (0 h) as well as 72 h post operation. To validate the results, urine samples from 71 patients who underwent cardiac surgery were collected, after which urinalysis was conducted to determine the microRNA concentration. An alternative expression profile of microRNAs was detected in rat urine. The quantitative validation of microRNA showed that the expression of miR-30c-5p, miR-192-5p, and miR-378a-3p was elevated significantly in urine post operation, which was consistent with those of the microarray analysis and earlier than kidney injury molecule-1 (KIM-1). In patients with acute kidney injury, increased levels of miR-30c-5p and miR-192-5p were also detected 2 h post operation, and miR-30c-5p showed preferable diagnostic value compared with protein-based biomarkers. In conclusion, an aberrant expression profile of microRNA was detected in rat urine based on the established ischemia-reperfusion animal model. Both miR-30c-5p and miR-192-5p served as important potential diagnostic markers for I/R-induced kidney injury. Impact statement Firstly, one differentiating factor in our study is that the candidate miRNAs were screened in a controlled animal model rather than in patients with acute kidney injury (AKI) to ensure the purity of the cause of disease and to avoid possible effects of comorbidities on the spectrum of urine miRNA. This ensured the presence of only the relevant candidate miRNA (that associated with I/R injury); and what's more, the alterative expression of miR-192-5p and miR-30c-5p in animal model, patients with AKI, and cell model was confirmed simultaneously, which is likely to be more convincing. Secondly, the candidate miRNAs were screened sequentially at regular time points, which covered the initiation, progression, and partial repair stages, thus ensuring that no significant miRNAs were omitted in the screening process, and miR-biomarkers in 2 h post operation showed preferable diagnostic performance.

Acute Kidney Injury in Septic Patients Treated by Selected Nephrotoxic Antibiotic Agents—Pathophysiology and Biomarkers—A Review

“…The results were validated with urine samples from 71 patients who underwent cardiac surgery. The elevation of miR-192-5p was detected earlier than KIM-1, that was previously established as a renal injury biomarker [ 64 ]. Some other experimental studies on miR-192-5p and renal diseases in association with diabetes, hypertension and drug nephrotoxicity, can be added to the complex clinical and pathophysiological review.…”

Rno-microRNA-30c-5p promotes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and targeting SIRT1

“…The promoting role of rno-miR-30c-5p on myocardial IR injury is consistent with that on I/R-induced kidney and spinal cord injury. Zhou et al 13 have proved that ron-miR-30c-5p is up-regulated in rats with I/R-induced kidney injury. Li et al 14 The stimuli can promote the phosphorylation and subsequent degradation of IκBα, and subsequently import the active NF-κB into the nucleus 26 .…”

“…MiR-30c-5p is another subtype of miR-30 that also involved in the process of IR injury. Zhou et al 13 have proved that rno-miR-30c-5p is a potential diagnostic marker for I/R-induced kidney injury in rats. Li et al 14 have shown that hydrogen sulfide protects spinal cord and induces autophagy in a rat model of spinal cord IR injury via regulating rno-miR-30c-5p.…”

MicroRNAs in AKI and Kidney Transplantation

“…miR-192 was assessed for diagnosis of AKI when sampled 2 hours after cardiac surgery; however, it had a rather poor sensitivity and specificity (45). Likewise, urinary miR-30c-5p performed well as a biomarker of AKI after cardiac surgery, and even better compared with protein-based markers such as neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (46). In contrast-induced nephropathy, miR-30a, c, and e appeared to be significantly higher in comparison with patients who received contrast but without nephropathy (47).…”