Identification, Confirmation, and Replication of Novel Urinary MicroRNA Biomarkers in Lupus Nephritis and Diabetic Nephropathy

Abstract

BACKGROUND The prevalence of chronic kidney disease (CKD) is increasing, leading to significant morbidity and mortality. Kidney biopsy remains the gold standard for diagnosing the underlying etiology of CKD, but the procedure carries complication risks. The aim of this study was to identify novel noninvasive biomarkers correlating with kidney function and histopathology in biopsyproven CKD patients. METHODS We profiled 2402 urinary microRNAs (miRNAs) to identify and confirm differentially expressed miRNAs associated with kidney function and histopathology in patients with diabetic nephropathy (n = 58) or lupus nephritis (n = 89), important etiologies of CKD, compared with healthy controls (n = 93 and 119, respectively). Top performing miRNAs were then measured in 2 independent multi-institutional cohorts of patients with diabetes mellitus with (n = 74) or without nephropathy (n = 71) and systemic lupus erythematosus with (n = 86) or without (n = 37) nephritis. RESULTS In patients with diabetic nephropathy, miR-2861, miR-1915-3p, and miR-4532 were down-regulated (>10-fold, P < 0.0001) and were associated with estimated glomerular filtration rate (P < 0.01) and interstitial fibrosis/tubular atrophy (P < 0.05). The c-statistics for miR-2861, miR-1915-3p, and miR-4532 were 0.91, 0.86, and 0.85, respectively. In lupus nephritis patients, miR-3201 and miR-1273e were down-regulated (>3-fold, P < 0.0001) and associated with endocapillary glomerular inflammation (P < 0.01), with c-statistics of 0.97 and 0.91, respectively. CONCLUSIONS We have identified novel miRNAs that correlate with histopathological lesions and functional markers of kidney damage to facilitate sensitive, specific, and noninvasive detection of diabetic nephropathy and lupus nephritis.

Extracellular RNA in systemic lupus erythematosus

“…However, in diabetic nephropathy, miR-4532, miR-1915-3p and miR-2861 were downregulated and associated with estimated glomerular filtration rate and interstitial fibrosis/tubular atrophy. This study for the first time showed that miRNAs can be used as biomarkers to distinguish LN and diabetic nephropathy [87].…”

“…exRNAs may take parts in the process of SLE and some of them can be used as diagnostic tool for SLE. lnc-DC ↓ [82] miR-22 ↓ Lupus nephritis [76] miR-15b ↓ [76] miR-151a-3p ↓ [84] miR-130b ↓ [86] miR-5571-5p ↓ [87] miR-766-3p ↓ [87]…”

MiRNA Extraction from Cell-Free Biofluid Using Protein Corona Formed around Carboxyl Magnetic Nanoparticles

“…Although most miRNAs are kept in cells, there are still plenty of miRNAs found in extracellular environment, such as serum, urine and breast milk. MiRNAs in urine have been exploited as a potential biomarker to diagnose multiple diseases like urinary system cancer, kidney injury and diabetes, and they have already been demonstrated many advantages as stable and noninvasive biomarkers for early stage detection 31–34 . However, the traditional method to extract miRNA from urine is cumbersome and costly.…”

The regulatory role of microRNAs in angiogenesis‐related diseases

“…215 215 Studies reported that the three decreased miR-NAs are related to increased levels of IFTA and tubulointerstitial inflammation, suggesting the role of these miRNAs in fibrosis formation in DN. 219 Notably, studies reported that miR-192 is increased in the early stage of DN patients but it is decreased in the late stage, 220 Among others, the detection of miRNAs in urine may act as a fresh non-invasive approach for diagnosis and dynamic monitoring of diabetic microvascular complication to especially improve the prediction, treatment and prognosis without the need for invasive diagnostic or radiological procedures.…”