Table 3.
Extracellular miRNAs as biomarkers of organ damage.a
| Disease | Body fluid | Candidate miRNAs | Cohorts used | Normalizer | Reference | ||
|---|---|---|---|---|---|---|---|
| Discovery | Confirmation | Evaluation | |||||
| AMI | Plasma | miR-1 | 93 AMI, 66 controls | 83 AMI temporal study | — | RNU6B | Creemers et al. (52) |
| Serum | miR-1 | 8 AMI, 8 controls rats temporal study | 12 AMI, 12 controls rats | 31 AMI, 20 controls humans | Blood volume | Creemers et al. (52) | |
| Plasma | miR-122, -375 | 6 ST-segment elevation MI (STEMI), 6 controls | 25 STEMI, 17 controls | 8 STEMI temporal study | Self-normalization | D’Alessandra et al. (122) | |
| Plasma | miR-208b, -499 | 36 AMI, 36 controls | 14 Acute viral myocarditis (VM), 20 post VM, 20 controls | 33 Acute heart failure, 20 controls | C. elegans miR-39 | Creemers et al. (52) | |
| Plasma | miR-208a | 4 Controls | 33 AMI, 16 coronary heart disease, 17 different cardiovascular diseases, 30 controls | 5 AMI before and after treatment | Raw data | Wang et al. (123) | |
| Plasma | miR-499 | 14 Acute coronary syndromes, 15 congestive heart failure, 10 controls | — | — | Synthetic small RNA | Creemers et al. (52) | |
| Urine | miR-1 | 8 AMI, 8 controls rats | 8 AMI, 8 controls rats, temporal study, serum, and urine | 20 AMI, 20 controls humans | Standard curve calibration | Cheng et al. (53) | |
| Acute kidney injury (AKI) | Plasma | miR-210 | Pooled 5 AKI, 5 controls | 77 AKI, 18 AMI, 30 controls | — | C. elegans miR-54 | Lorenzen et al. (34) |
| Urine | miR-21, -200c, - 423, -4640 | Pooled 6 AKI, 6 controls | 6 AKI and 6 healthy controls | 98 AKI, 97 controls | miR-1287 | Ramachandran et al. (36) | |
| Chronic kidney disease (CKD) | Plasma and Urine | miR-16, -155, -210, -638 | 33 CKD, 22 controls - plasma | 12 CKD, 7 controls - urine | — | Raw data | Neal et al. (20) |
| Acute allograft rejection | Urine | miR-10a, -10b, -210 | Pooled 5 rejection, 5 stable transplant | 68 Rejection, 20 stable transplant, 13 UTI after transplant | 19 Before and after rejection | C. elegans miR-39 | Lorenzen et al. (54) |
| Chronic allograft dysfunction (CAD) | Urine | miR-142–3p, -204, -211 | 13 CAD, 5 controls tissue | 7 CAD, 7 controls | 36 Transplant recipients temporal study | RNU48 | Scian et al. (124) |
| ESRD | Plasma | miR-638, -21, -155, -210, -16 | 20 ESRD, 33 CKD, 22 controls | — | — | Raw data | Neal et al. (20) |
| Acetaminophen (APAP)- induced acute liver injury (ALI) | Serum | miR-122 | 6 APAP–no ALI, 11 no APAP–ALI, 22 CKD, 53 APAP–ALI, 25 controls, | 53 APAP–ALI prospective study | 11 APAP–ALI temporal study, 3 APAP–ALI before and after transplant | RNU6B | Starkey Lewis et al. (56) |
| Liver fibrosis | Serum | miR-29a | 5 Fibrotic, 5 control mouse tissue | 11 Fibrotic, 9 controls human tissue | 67 Fibrosis, 17 controls | RNU6B | Roderburg et al. (125) |
| Chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) | Serum | miR-34a, -122, -16 | 18 CHC, 19 controls | 35 CHC | 34 NAFLD, 19 controls | C. elegans miR- 238 | Cermelli et al. (57) |
| Active pulmonary tuberculosis (TB) | Sputum | miR-3179, -147, 19b-2* | Pooled 58 TB, 32 controls | 30 TB, 30 controls | - | RNU6B | Yi et al. (126) |
| Serum | miR-29a | Pooled 30 TB, 30 controls | 30 TB, 30 controls | 30 TB; 30 controls, sputum | RNU6B | Fu et al. (127) | |
| Biliary atresia (BA) | Serum | miR-200b, -429 | 5 BA, 5 controls | 24 BA, 24 controls | — | C.el-miR-54, -238 | Zahm et al. (128) |
a
List of 11 different types of organ damages in which microRNAs have been evaluated as biomarkers. Each row describes the detection matrix, study design, and normalization method used. Discovery and confirmation steps were typically performed in a cohort with a smaller sample size to select/verify candidate miRNAs, and evaluation was conducted in an expanded cross-sectional or longitudinal cohort to test the specificity, sensitivity, or early diagnostic capability. Studies were conducted using human biospecimens unless otherwise stated.