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

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.