Exploring urinary biomarkers in autosomal dominant polycystic kidney disease

• Published in: Clinical and experimental nephrology Vol. 19; no. 5; pp. 968 - 973
• Main Authors: Kawano, Haruna, Muto, Satoru, Ohmoto, Yasukazu, Iwata, Fusako, Fujiki, Hiroyuki, Mori, Toyoki, Yan, Lu, Horie, Shigeo
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2015; Springer Nature B.V
• Subjects: 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; Medicine; Medicine & Public Health; Mice, Inbred DBA; Middle Aged; Nephrology; Oncogene Proteins - genetics; Original Article; Polycystic Kidney, Autosomal Dominant - genetics; Polycystic Kidney, Autosomal Dominant - urine; Proto-Oncogene Proteins - genetics; Reproducibility of Results; Urology; Young Adult; Urinary biomarker; Autosomal dominant polycystic kidney disease; DBA/2FG-pcy mouse
• ISSN: 1342-1751; 1437-7799; 1437-7799
• DOI: 10.1007/s10157-014-1078-7

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.