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

Abstract

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.

Dietary Sodium Restriction Reduces Arterial Stiffness, Vascular TGF-β-Dependent Fibrosis and Marinobufagenin in Young Normotensive Rats

“…This statement is also supported by our observation that MBG stimulates collagen production in parallel with activation of TGFβ-1 in cultured VSMC in vitro, i.e., in the absence of hemodynamic effects. Our present findings are in agreement with the findings of previous studies that HS stimulates MBG production [ 17 , 18 , 19 , 33 , 34 ], activates TGFβ signaling in vasculature [ 28 , 29 ], and that HS intake can be a pressure-independent event in normotensive young subjects [ 32 , 33 , 35 , 36 , 37 ].…”

“…Notably, no significant changes in collagen deposition were observed in the renal cortex or medulla, and only a tendency for collagen increase around the small renal blood vessels was found in the cortex of the animals on an HS intake. Previous publications have documented an increase in the renal fibrosis in rats on an HS intake; the difference between our present study’s experimental setting and the settings in these publications are in the dietary salt amount (8% vs. 4% in our study) [ 30 , 36 , 41 ], or in the gender of the studied animals (females vs. males in the present study) [ 42 ].…”

Maternal Intake of Flaxseed During Lactation and Exercise Training Protect Against Salt Overload-Induced Aortic Remodeling in Adult Offspring

“…Although salt intake in the diet is recognized as a contributing factor to the pathogenesis of hypertension, recent evidence suggests that salt intake in the diet may increase the risk of adverse cardiovascular events regardless of blood pressure. 30,31 This is in accordance with our results, showing that the offspring that received 1% NaCl solution, both of control rat dams and mothers who received the flaxseed diet, showed no increase in blood pressure throughout the study. Similar findings were obtained by offering oral NaCl at 1% 32 or a diet with 1.3% NaCl, 33 which did not result in an increase in systolic blood pressure in normotensive rats.…”

Új szempontok a sószenzitív hypertoniák patomechanizmusában

“…A morfológiai változásokat a korai tubuluslaesiót jelző markerek (neutrophil gelatinase-associated lipocalin; NGAL és vanin-1; pantetheinase), a vizelet koncentrációjának szignifikáns emelkedése kíséri. Patofiziológiai szempontból különösen jelentős a vanin-1 emelkedése, mivel ez az enzim a ciszteamin képződését katalizálja, ami az antioxidáns enzimek aktivitását csökkentve hozzájárul a szövetek szabadgyök-károsodásához [48].…”