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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Characterization of renal biomarkers for use in clinical trials: effect of preanalytical processing and qualification

David A Brott1, Stephen T Furlong1, Scott H Adler1

  • 1Enabling Safety Sciences, Wilmington, DE, USA.

Drug Design, Development and Therapy
|July 1, 2015
PubMed
Abstract

Insights

New urine biomarkers show promise for detecting kidney injury in diabetes patients. Alpha-1-microglobulin (A1M) accurately distinguished between healthy volunteers and patients with diabetes mellitus, indicating potential for monitoring drug efficacy.

Area of Science:

  • Nephrology
  • Clinical Chemistry
  • Toxicology

Background:

  • Drug-induced kidney injury (DIKI) identification is critical for new drug development.
  • Preclinical DIKI biomarkers are qualified, but clinical biomarkers require further validation.
  • This study evaluated urinary biomarkers in healthy volunteers and patients with diabetes mellitus.

Purpose of the Study:

  • To investigate the utility of various urinary biomarkers for detecting kidney injury.
  • To assess biomarker performance in healthy volunteers (HV) with and without urine stabilizer.
  • To evaluate biomarker levels in patients with normoalbuminuric diabetes mellitus (P-DM).

Main Methods:

  • Analyzed urine samples from 20 HV with stabilizer, 69 HV without stabilizer, and 95 P-DM without stabilizer.
  • Utilized multiplex assays to measure 16 biomarkers including α-1-microglobulin (A1M), connective tissue growth factor (CTGF), glutathione S-transferase α (GSTα), kidney injury marker-1 (KIM-1), and others.
  • Determined "expected values" and compared biomarker levels between groups.

Main Results:

  • CTGF and GSTα assays were suboptimal in non-stabilized urine.
  • Significant differences in A1M, CTGF, GSTα, and THP were observed between HV with and without stabilizer.
  • P-DM urine showed elevated levels of A1M, CTGF, GSTα, KIM-1, microalbumin, osteopontin, and TFF3 compared to HV.
  • A1M demonstrated 89.0% accuracy in distinguishing P-DM from HV.

Conclusions:

  • Non-stabilized urine is suitable for qualifying assays.
  • A1M, CTGF, GSTα, KIM-1, microalbumin, osteopontin, and TFF3 are significantly increased in P-DM urine.
  • A1M shows potential as a biomarker for monitoring renal protective agent efficacy in P-DM.
Keywords:
drug developmenthealthy volunteerskidney

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