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Circulating Micro RNA ‐ 188, ‐ 30a, and ‐ 30e as Early Biomarkers for Contrast ‐ Induced Acute Kidney Injury

View Article: PubMed Central - PubMed

ABSTRACT

Background: Contrast‐induced acute kidney injury (CI‐AKI) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating microRNAs (miRNAs) could serve as biomarkers for early detection of CI‐AKI.

Methods and results: Using a rat model of CI‐AKI, we first evaluated the miRNA profile of rat plasma and kidney. Three miRNA species with >1.5‐fold increase in plasma samples of CI‐AKI rats, including miRNA‐188, miRNA‐30a, and miRNA‐30e, were selected as candidate miRNAs. Quantitative real‐time polymerase chain reaction showed that these candidate miRNAs peaked in concentration around 4 hours after contrast medium exposure and were relatively renal‐specific. We compared the plasma levels of these candidate miRNAs in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed CI‐AKI with those of 71 matched controls. The plasma levels of the 3 candidate miRNAs were significantly elevated in the CI‐AKI group as compared to the control group. Receiver operating characteristic analysis showed that these miRNAs significantly distinguished patients with CI‐AKI from those without CI‐AKI. MiRNA composites were highly accurate for CI‐AKI prediction, as shown in maximized specificity by treble‐positive miRNA composite or maximized Youden index by any‐positive miRNA composite. Moreover, the selected miRNAs changes were associated with Mehran Risk Scores.

Conclusions: Plasma levels of candidate miRNAs significantly distinguished patients with CI‐AKI from those without CI‐AKI. Thus, miRNAs are potential biomarkers for early detection of CI‐AKI.

No MeSH data available.


Related in: MedlinePlus

Candidate circulating miRNAs were associated with Mehran Risk Scores. A, Comparison of mean Mehran Risk Scores and incidence of Mehran Risk Score ≥6 between CI‐AKI and non‐CI‐AKI patients by different CI‐AKI criteria. B, Mean Mehran Risk Score and incidence of Mehran Risk Score ≥6 in 4 categories of patients. +/+ indicates patients who met the CI‐AKI criteria based both on miRNA and CyC/SCr; +/− indicates patients who met the CI‐AKI criteria based on miRNA but not CyC/SCr; −/+ indicates patients who met the CI‐AKI criteria based on CyC/SCr but not miRNA; −/− indicates patients who did not meet the CI‐AKI criteria based both on miRNA and CyC/SCr. Any‐positive, the fold‐change of any 1 of the 3 selected miRNAs reaching cutoff point I; treble‐positive, the fold‐change of all 3 selected miRNAs reaching cutoff point I. Error is represented as SEM. **P<0.01. ***P<0.001. CI‐AKI indicates contrast‐induced acute kidney injury; CyC/SCr, cystatin C/serum creatinine; miRNA, microRNA.
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jah31704-fig-0004: Candidate circulating miRNAs were associated with Mehran Risk Scores. A, Comparison of mean Mehran Risk Scores and incidence of Mehran Risk Score ≥6 between CI‐AKI and non‐CI‐AKI patients by different CI‐AKI criteria. B, Mean Mehran Risk Score and incidence of Mehran Risk Score ≥6 in 4 categories of patients. +/+ indicates patients who met the CI‐AKI criteria based both on miRNA and CyC/SCr; +/− indicates patients who met the CI‐AKI criteria based on miRNA but not CyC/SCr; −/+ indicates patients who met the CI‐AKI criteria based on CyC/SCr but not miRNA; −/− indicates patients who did not meet the CI‐AKI criteria based both on miRNA and CyC/SCr. Any‐positive, the fold‐change of any 1 of the 3 selected miRNAs reaching cutoff point I; treble‐positive, the fold‐change of all 3 selected miRNAs reaching cutoff point I. Error is represented as SEM. **P<0.01. ***P<0.001. CI‐AKI indicates contrast‐induced acute kidney injury; CyC/SCr, cystatin C/serum creatinine; miRNA, microRNA.

Mentions: The Mehran Risk Score was capable of predicting CI‐AKI occurrence and prognosis. Correlation analysis revealed that the change of candidate miRNAs postprocedure was significantly related with the Mehran Risk Score (P<0.05, Figure S1B). The mean Mehran Risk Score and the proportion of patients with a score ≥6 were higher in the group with elevated miRNAs postprocedure indicating CI‐AKI (CI‐AKImiRNA group) compared with the group that did not have significantly elevated miRNA levels (non‐CKI‐AKImiRNA group); however, no significant difference in Mehran Risk Scores between the CI‐AKI group defined by SCr/CyC (CI‐AKISCr/CyC) and non‐CI‐AKISCr/CyC group was found (Figure 4A). Comparing with CI‐AKISCr/CyC (+)/CI‐AKImiRNA (−) patients, patients with CI‐AKImiRNA (+)/CI‐AKISCr/CyC (−) had higher Mehran Risk Scores and a higher proportion of patients with Mehran Risk Scores ≥6 (Figure 4B). These results indicated that the 3 candidate miRNAs might be more capable of detecting patients at real danger of CI‐AKI than the traditional biomarkers.


Circulating Micro RNA ‐ 188, ‐ 30a, and ‐ 30e as Early Biomarkers for Contrast ‐ Induced Acute Kidney Injury
Candidate circulating miRNAs were associated with Mehran Risk Scores. A, Comparison of mean Mehran Risk Scores and incidence of Mehran Risk Score ≥6 between CI‐AKI and non‐CI‐AKI patients by different CI‐AKI criteria. B, Mean Mehran Risk Score and incidence of Mehran Risk Score ≥6 in 4 categories of patients. +/+ indicates patients who met the CI‐AKI criteria based both on miRNA and CyC/SCr; +/− indicates patients who met the CI‐AKI criteria based on miRNA but not CyC/SCr; −/+ indicates patients who met the CI‐AKI criteria based on CyC/SCr but not miRNA; −/− indicates patients who did not meet the CI‐AKI criteria based both on miRNA and CyC/SCr. Any‐positive, the fold‐change of any 1 of the 3 selected miRNAs reaching cutoff point I; treble‐positive, the fold‐change of all 3 selected miRNAs reaching cutoff point I. Error is represented as SEM. **P<0.01. ***P<0.001. CI‐AKI indicates contrast‐induced acute kidney injury; CyC/SCr, cystatin C/serum creatinine; miRNA, microRNA.
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jah31704-fig-0004: Candidate circulating miRNAs were associated with Mehran Risk Scores. A, Comparison of mean Mehran Risk Scores and incidence of Mehran Risk Score ≥6 between CI‐AKI and non‐CI‐AKI patients by different CI‐AKI criteria. B, Mean Mehran Risk Score and incidence of Mehran Risk Score ≥6 in 4 categories of patients. +/+ indicates patients who met the CI‐AKI criteria based both on miRNA and CyC/SCr; +/− indicates patients who met the CI‐AKI criteria based on miRNA but not CyC/SCr; −/+ indicates patients who met the CI‐AKI criteria based on CyC/SCr but not miRNA; −/− indicates patients who did not meet the CI‐AKI criteria based both on miRNA and CyC/SCr. Any‐positive, the fold‐change of any 1 of the 3 selected miRNAs reaching cutoff point I; treble‐positive, the fold‐change of all 3 selected miRNAs reaching cutoff point I. Error is represented as SEM. **P<0.01. ***P<0.001. CI‐AKI indicates contrast‐induced acute kidney injury; CyC/SCr, cystatin C/serum creatinine; miRNA, microRNA.
Mentions: The Mehran Risk Score was capable of predicting CI‐AKI occurrence and prognosis. Correlation analysis revealed that the change of candidate miRNAs postprocedure was significantly related with the Mehran Risk Score (P<0.05, Figure S1B). The mean Mehran Risk Score and the proportion of patients with a score ≥6 were higher in the group with elevated miRNAs postprocedure indicating CI‐AKI (CI‐AKImiRNA group) compared with the group that did not have significantly elevated miRNA levels (non‐CKI‐AKImiRNA group); however, no significant difference in Mehran Risk Scores between the CI‐AKI group defined by SCr/CyC (CI‐AKISCr/CyC) and non‐CI‐AKISCr/CyC group was found (Figure 4A). Comparing with CI‐AKISCr/CyC (+)/CI‐AKImiRNA (−) patients, patients with CI‐AKImiRNA (+)/CI‐AKISCr/CyC (−) had higher Mehran Risk Scores and a higher proportion of patients with Mehran Risk Scores ≥6 (Figure 4B). These results indicated that the 3 candidate miRNAs might be more capable of detecting patients at real danger of CI‐AKI than the traditional biomarkers.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Contrast&#8208;induced acute kidney injury (CI&#8208;AKI) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating microRNAs (miRNAs) could serve as biomarkers for early detection of CI&#8208;AKI.

Methods and results: Using a rat model of CI&#8208;AKI, we first evaluated the miRNA profile of rat plasma and kidney. Three miRNA species with &gt;1.5&#8208;fold increase in plasma samples of CI&#8208;AKI rats, including miRNA&#8208;188, miRNA&#8208;30a, and miRNA&#8208;30e, were selected as candidate miRNAs. Quantitative real&#8208;time polymerase chain reaction showed that these candidate miRNAs peaked in concentration around 4&nbsp;hours after contrast medium exposure and were relatively renal&#8208;specific. We compared the plasma levels of these candidate miRNAs in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed CI&#8208;AKI with those of 71 matched controls. The plasma levels of the 3 candidate miRNAs were significantly elevated in the CI&#8208;AKI group as compared to the control group. Receiver operating characteristic analysis showed that these miRNAs significantly distinguished patients with CI&#8208;AKI from those without CI&#8208;AKI. MiRNA composites were highly accurate for CI&#8208;AKI prediction, as shown in maximized specificity by treble&#8208;positive miRNA composite or maximized Youden index by any&#8208;positive miRNA composite. Moreover, the selected miRNAs changes were associated with Mehran Risk Scores.

Conclusions: Plasma levels of candidate miRNAs significantly distinguished patients with CI&#8208;AKI from those without CI&#8208;AKI. Thus, miRNAs are potential biomarkers for early detection of CI&#8208;AKI.

No MeSH data available.


Related in: MedlinePlus