Early urinary biomarkers of renal tubular damage by a high‐salt intake independent of blood pressure in normotensive rats

• Published in: Clinical and experimental pharmacology & physiology 2018-03, Vol.45 (3), p.261-268
• Main Authors: Washino, Satoshi, Hosohata, Keiko, Jin, Denan, Takai, Shinji, Miyagawa, Tomoaki
• Format: Article
• Language: English
• Subjects: Acute-Phase Proteins - urine; Age; Aging; Animal Feed; Animal tissues; Animals; Biomarkers; Biomarkers - urine; Blood pressure; Blood Pressure - physiology; Creatinine; Damage; Diet; Dietary intake; Dose-Response Relationship, Drug; Drug Administration Schedule; early biomaker; Gelatinase; Glucosaminidase; high‐salt intake; Hypertension; Kidney Diseases - chemically induced; Kidney Tubules - pathology; Lipocalin; Lipocalins - urine; normotensive; Proto-Oncogene Proteins - urine; Rac1; Rac1 protein; Rats; Rats, Inbred WKY; renal tubular damage; Rodents; Salt; Salts; Sodium; Sodium chloride; Sodium Chloride - administration & dosage; Sodium Chloride - toxicity; Sodium Chloride, Dietary - administration & dosage; Sodium Chloride, Dietary - toxicity; Urine; Wistar Kyoto rats
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12871

Summary Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) as well as hypertension. A high‐salt intake causes renal damage independent of hypertension. Because traditional renal biomarkers are insensitive, it is difficult to detect renal injury induced by a high‐salt intake, especially in normotensive patients. Here, we investigated whether newly developed renal biomarkers could be detected earlier than traditional biomarkers under a high‐salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY) received a regular (0.8% NaCl) or salt‐loaded (2, 4, and 8% NaCl) diet from 9 to 17 weeks of age. A urine sample was obtained once a week and urinary vanin‐1, neutrophil gelatinase‐associated lipocalin (NGAL), and kidney injury molecule‐1 (Kim‐1) were measured. At 17 weeks of age, 8% salt‐loaded WKY showed histopathological renal tubular damage and elevated Rac1 activity in renal tissues. Although there was no significant increase in serum creatinine, urinary albumin, N‐acetyl‐β‐D‐glucosaminidase (NAG), or Kim‐1 during the study period among the groups, urinary vanin‐1 and NGAL significantly increased in 8% salt‐loaded WKY from 10 to 17 weeks of age. These results suggest that urinary vanin‐1 and NGAL, which might be induced by salt per se, are potentially earlier biomarkers for renal tubular damage in normotensive rats under a high‐salt intake.