Abstract
High-salt intake leads to kidney damage and even limits the effectiveness of drugs. However, it is unclear whether excessive intake of salt affects renal tubular energy metabolism and the efficacy of dapagliflozin on renal function in diabetic kidney disease (DKD). In this study, we enrolled 350 DKD patients and examined the correlation between sodium level and renal function, and analyzed influencing factors. The results demonstrated that patients with macroalbuminuria have higher 24 h urinary sodium levels. After establishment of type 2 diabetes mellitus model, the animals received a high-salt diet or normal-salt diet. In the presence of high-salt diet, the renal fibrosis was aggravated with fatty acid metabolism dysregulation. Furthermore, Na+/K+-ATPase expression was up-regulated in the renal tubules of diabetic mice, while the fatty acid metabolism was improved by inhibiting Na+/K+-ATPase of renal tubular epithelial cells. Of note, the administration with dapagliflozin improved renal fibrosis and enhanced fatty acid metabolism. But high salt weakened the above-mentioned renal protective effects of dapagliflozin in DKD. Similar results were recapitulated in vitro after incubating proximal tubular epithelial cells in high-glucose and high-salt medium. In conclusion, our results indicate that high salt can lead to fatty acid metabolism disorders by increasing Na+/K+-ATPase expression in the renal tubules of DKD. High salt intake diminishes the reno-protective effect of dapagliflozin in DKD.
Highlights
The World Health Organization recommended to reduce salt intake to less than 5 g/day of salt (Brown et al, 2009)
Binary logistic regression analysis indicated that low-density lipoprotein (LDL)-cholesterol, duration of diabetes, systolic blood pressure, serum uric acid and 24 h-UNa excretion were all significantly associated with the degree of albuminuria
We conducted a retrospective study of patients with diabetic kidney disease (DKD) and we found that patients with macroalbuminuria have higher levels of 24 h-UNa compared with patients with microalbuminuria
Summary
The World Health Organization recommended to reduce salt intake to less than 5 g/day of salt (Brown et al, 2009). The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF/KDOQI) supports the recommendation of salt intake restriction (Inker et al, 2014). Salt consumption is still high (Brown et al, 2009). A high-salt intake is associated with the development of many diseases. Based on the 24-h urine sodium (24 h-UNa) excretion, it was estimated that average salt intake of chronic kidney disease (CKD) patients is 9.5 g/day (de Borst and Navis, 2016). Altered dietary salt intake is noted to prevent and treat CKD (Lankhorst et al, 2016; Mcmahon et al, 2021). A high-salt diet (HSD) leads to increased biomarkers of renal tubular damage, not
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