Dataset Information

Urinary microRNA-10a and microRNA-30d serve as novel, sensitive and specific biomarkers for kidney injury.

ABSTRACT: The steadily increasing incidence of kidney injury is a significant threat to human health. The current tools available for the early detection of kidney injury, however, have limited sensitivity or specificity. Thus, the development of novel biomarkers to detect early kidney injury is of high importance. Employing mouse renal ischemia-reperfusion and streptozotocin (STZ)-induced renal injury as acute and chronic kidney injury model, respectively, we assessed the alteration of microRNA (miRNA) in mouse urine, serum and kidney tissue by TaqMan probe-based qRT-PCR assay. Our results demonstrated that kidney-enriched microRNA-10a (miR-10a) and microRNA-30d (miR-30d) were readily detected in mouse urine and the levels of urinary miR-10a and miR-30d were positively correlated with the degree of kidney injury induced by renal ischemia-reperfusion or STZ diabetes. In contrast, no such alteration of miR-10a and miR-30d levels was observed in mouse serum after kidney injury. Compared with the blood urea nitrogen (BUN) assay, the test for urinary miR-10a and miR-30d levels was more sensitive for the detection of acute kidney injury. Furthermore, the substantial elevation of the urinary miR-10a and miR-30d levels was also observed in focal segmental glomerulosclerosis (FSGS) patients compared to healthy donors. In conclusion, the present study collectively demonstrates that urinary miR-10a and miR-30d represent a novel noninvasive, sensitive, specific and potentially high-throughput method for detecting renal injury.

SUBMITTER: Wang N

PROVIDER: S-EPMC3521774 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Urinary microRNA-10a and microRNA-30d serve as novel, sensitive and specific biomarkers for kidney injury.

Wang Nan N Zhou Yang Y Jiang Lei L Li Donghai D Yang Junwei J Zhang Chen-Yu CY Zen Ke K

PloS one 20121213 12

The steadily increasing incidence of kidney injury is a significant threat to human health. The current tools available for the early detection of kidney injury, however, have limited sensitivity or specificity. Thus, the development of novel biomarkers to detect early kidney injury is of high importance. Employing mouse renal ischemia-reperfusion and streptozotocin (STZ)-induced renal injury as acute and chronic kidney injury model, respectively, we assessed the alteration of microRNA (miRNA) i ...[more]

PMID: 23272089

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Project description: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.

Project description:Vancomycin has been associated with acute kidney injury in preclinical and clinical settings; however, the precise exposure profiles associated with vancomycin-induced acute kidney injury have not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kidney injury using sensitive urinary biomarkers. Male Sprague-Dawley rats received clinical-grade vancomycin or normal saline as an intraperitoneal injection. Total daily doses between 0 and 400 mg/kg of body weight were administered as a single dose or 2 divided doses over a 24-h period. At least five rats were utilized for each dosing protocol. A maximum of 8 plasma samples per rat were obtained, and urine was collected over the 24-h period. Kidney injury molecule-1 (KIM-1), clusterin, osteopontin, cystatin C, and neutrophil gelatinase-associated lipocalin levels were determined using Milliplex multianalyte profiling rat kidney panels. Vancomycin plasma concentrations were determined via a validated high-performance liquid chromatography methodology. Pharmacokinetic analyses were conducted using the Pmetrics package for R. Bayesian maximal a posteriori concentrations were generated and utilized to calculate the 24-h area under the concentration-time curve (AUC), the maximum concentration (Cmax), and the minimum concentration. Spearman's rank correlation coefficient (rs ) was used to assess the correlations between exposure parameters, biomarkers, and histopathological damage. Forty-seven rats contributed pharmacokinetic and toxicodynamic data. KIM-1 was the only urinary biomarker that correlated with both composite histopathological damage (rs = 0.348, P = 0.017) and proximal tubule damage (rs = 0.342, P = 0.019). The vancomycin AUC and Cmax were most predictive of increases in KIM-1 levels (rs = 0.438 and P = 0.002 for AUC and rs = 0.451 and P = 0.002 for Cmax). Novel urinary biomarkers demonstrate that kidney injury can occur within 24 h of vancomycin exposure as a function of either AUC or Cmax.

Dataset Information

Urinary microRNA-10a and microRNA-30d serve as novel, sensitive and specific biomarkers for kidney injury.

Publications

Urinary microRNA-10a and microRNA-30d serve as novel, sensitive and specific biomarkers for kidney injury.

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