Abstract: FR-PO729

Urine Micro-RNAs as Histology Biomarkers in Lupus Nephritis

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Zhang, Xiaolan, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Mejia-Vilet, Juan M., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico
  • Song, Huijuan, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Parikh, Samir V., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Satoskar, Anjali A., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Nadasdy, Tibor, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center , Columbus, Ohio, United States

Group or Team Name

  • CKD Biomarker Consortium
Background

Urine micro-RNAs (miRNA) have emerged as potential biomarkers for lupus nephritis (LN). The relationship of urine miRNAs with renal histology in LN was investigated.

Methods

This study examined 98 biopsy-proven LN patients and 19 healthy controls. Total urine RNA was enriched using ExoQuick columns. miRNA was extracted and screened for differential expression of individual miRNAs between LN and controls using Nanostring miRNA profiling. The miRNAs showing the most significant differential expression on screening were validated by duplex real-time PCR after cDNA synthesis using a TaqMan Advanced miRNA cDNA Synthesis kit. miRNA levels were normalized to urine creatinine and the housekeeping miRNA, miR-191-5p. Urine miRNA expression and kidney histology were compared by t-test, ANOVA followed by Wilcoxon ranked-sum testing or multiple linear regression, as appropriate.

Results

Several miRNAs identified by Nanostring screening were confirmed by PCR. Of these, miR-29c-3p correlated with kidney biopsy chronicity index (R2=0.38, p=0.0022), and was significantly increased in the urine of patients with interstitial fibrosis (4.86-fold; p=0.006) and tubular atrophy (5.92-fold; p=0.0029). miR-1290 expression was 39-fold higher (p=0.007) in patients who did not have crescents compared to those with crescents. miR-200b-3p was also decreased in patients with crescents (7.78-fold; P=0.024), glomerular neutrophil accumulation (10-fold; P=0.006) and endocapillary proliferation (2.82-fold, P=0.01) compared to patients without these acute lesions.

Conclusion

A subset of miRNAs that are differentially-expressed in the urine of LN patients appear to correlate with acute or chronic changes on kidney biopsy and are candidate renal histology biomarkers that may be useful for non-invasively following changes in renal pathology during LN.

Funding

  • NIDDK Support