Haruna Kawano1,2, Satoru Muto3,2, Yasukazu Ohmoto4, Fusako Iwata4, Hiroyuki Fujiki4, Toyoki Mori4, Lu Yan3, Shigeo Horie5,6,7. 1. Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan. 2. Department of Advanced Therapeutics of Polycystic Kidney Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan. 3. Department of Urology, Teikyo University School of Medicine, Tokyo, Japan. 4. Research Institute of Pharmacological Therapeutical Development, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan. 5. Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan. shorie@juntendo.ac.jp. 6. Department of Urology, Teikyo University School of Medicine, Tokyo, Japan. shorie@juntendo.ac.jp. 7. Department of Advanced Therapeutics of Polycystic Kidney Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan. shorie@juntendo.ac.jp.
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.
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 ADPKDpatients, 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 ADPKDpatients 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 ADPKDpatients 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.
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