Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis

Subham Dasgupta1, Tatiana Sharapova2, Prathap K Mahalingaiah2

  • 1Department of Biological Sciences, Clemson University, Clemson, SC, USA.

Insights

Urinary microRNAs (miRNAs) show promise as early biomarkers for drug-induced kidney injury (DIKI). Specific miRNAs correlated with kidney damage in preclinical models, suggesting potential for early DIKI detection in clinical trials.

Area of Science:

  • Nephrology
  • Biomarker Discovery
  • Pharmacology

Background:

  • Drug-induced kidney injury (DIKI) is kidney damage from medications.
  • Early detection of DIKI is crucial for patient outcomes.
  • Urinary microRNAs (miRNAs) are being investigated as non-invasive biomarkers.

Purpose of the Study:

  • Identify urinary miRNA biomarkers for predicting DIKI before clinical diagnosis.
  • Evaluate specific miRNAs (miR-210-3p, -423-5p, -143-3p, -130b-3p, -486-5p, -193a-3p) as DIKI predictors.
  • Compare exosome-associated miRNAs with whole urine miRNAs for DIKI detection.

Main Methods:

  • Quantified six specific miRNAs in urinary samples from cynomolgus monkeys exposed to a nephrotoxicant.
  • Analyzed miRNA levels across multiple time points post-exposure.
  • Correlated miRNA levels with histopathology scores of kidney damage.

Main Results:

  • Distinct trends observed between exosome-associated miRNAs and whole urine miRNAs.
  • Several urinary miRNAs showed strong correlations with kidney histopathology scores.
  • These findings suggest potential predictive value for specific miRNAs in DIKI.

Conclusions:

  • Urinary miRNAs, particularly exosome-associated ones, may serve as early predictive biomarkers for DIKI.
  • The identified miRNAs hold potential for preclinical and clinical applications in DIKI detection.
  • Further research is needed to elucidate miRNA mechanisms in DIKI pathogenesis.