Exploring urinary biomarkers in autosomal dominant polycystic kidney disease

Clin Exp Nephrol. 2015 Oct;19(5):968-73. doi: 10.1007/s10157-014-1078-7. Epub 2014 Dec 28.

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disease, is a progressive disease characterized by a bilateral proliferation and enlargement of renal cysts. Recent reports have shown that tolvaptan, a vasopressin V2 receptor antagonist, has been effective in inhibiting renal cyst proliferation and enlargement in ADPKD patients, although no biomarker has identified to predict the effects of tolvaptan. We explored the effective urinary biomarkers in ADPKD in human and in an animal model.

Methods: We measured 28 biomarkers in urine taken from ADPKD patients to compare with that of healthy subjects. Next, a gene expression analysis of the kidney from DBA/2FG-pcy mice (ADPKD model animals) was performed to identify prospective biomarkers. Additionally, we investigated the DBA/2FG-pcy mouse urine samples to determine the biomarkers' efficacy.

Results: There were statistically significant differences in 12 of the 28 prospective urinary biomarkers between urine from ADPKD patients and that from healthy subjects. Six of these matched with highly expressed gene products of DBA/sFG-pcy mouse kidneys. Among those 6 biomarkers, NGAL, M-CSF, and MCP-1 showed significantly higher values in the urine of DBA/2FG-pcy mice than that of wild type.

Conclusions: This study suggests that NGAL, M-CSF, MCP-1 are potential candidates of urinary biomarkers in ADPKD.

Keywords: Autosomal dominant polycystic kidney disease; DBA/2FG-pcy mouse; Urinary biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Adult
  • Animals
  • Biomarkers / urine
  • Chemokine CCL2 / genetics
  • Colony-Stimulating Factors / genetics
  • Female
  • Gene Expression / genetics
  • Humans
  • Lipocalin-2
  • Lipocalins / genetics
  • Male
  • Mice, Inbred DBA
  • Middle Aged
  • Oncogene Proteins / genetics
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / urine*
  • Proto-Oncogene Proteins / genetics
  • Reproducibility of Results
  • Young Adult

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • CCL2 protein, human
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Colony-Stimulating Factors
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Lcn2 protein, mouse