High salt diet (HSD), considered a public health problem worldwide, is associated with chronic degenerative diseases including renal diseases. However, little is known about the effects of HSD on renal function independently of the development of hypertension. To address the hypothesis that HSD induces renal injuries even without changes in blood pressure, BALB/c mice were fed for 7 days with chow with a high salt content (0.3–8%). Blood pressure did not change and there was a decrease in cortical (Na⁺ + K⁺)ATPase and NHE3 exchanger and an increase in renal fractional excretion of sodium. Positive correlations between Na⁺ intake or urinary sodium excretion with proteinuria were found. HSD did not change glomerular function and structure, but induced tubule-interstitial injury measured by an increase in collagen deposition, interstitial space and γ-GT activity, a marker of tubular injury. These effects were associated with a decrease in cortical albumin reabsorption and megalin expression. Similarly, the addition of NaCl 20 mM to the incubation medium of LLC-PK1 cells reduced megalin expression and albumin endocytosis indicating that HSD could have a direct effect on proximal tubule cells. Furthermore, tubule-interstitial injury was associated with pro-inflammatory and pro-fibrotic phenotypes with an increase in Th1 and Th17 phenotypes and a decrease in Tregs followed by increases in IL-6, -17, -10, TNF-α, IFN-γ and TGF-β. Our results reveal a complex network involved in renal injuries induced by HSD independently of changes in blood pressure. These findings strengthen the importance of restriction of salt intake for the general population even for salt-resistant individuals.

高盐饮食（HSD）被认为是全球范围内的公共健康问题，与包括肾脏疾病在内的慢性退行性疾病有关。然而，关于HSD对肾功能的影响与高血压的发展无关，所知甚少。为了解决HSD甚至在血压无变化的情况下也能引起肾损伤的假设，对BALB / c小鼠喂食了7天高盐含量（0.3–8％）的松鼠。血压没有变化，皮质（Na ⁺  + K ⁺）ATPase和NHE3交换子减少，肾脏钠分数排泄增加。Na ⁺之间的正相关发现摄入量或尿钠排泄与蛋白尿有关。HSD不会改变肾小球的功能和结构，但可通过胶原沉积，间质间隙和γ-GT活性（一种肾小管损伤的标志物）的增加来衡量，从而引起肾小管间质损伤。这些作用与皮质白蛋白重吸收和巨蛋白表达的降低有关。同样，向LLC-PK1细胞的培养液中添加20 mM NaCl会降低巨蛋白表达和白蛋白内吞作用，这表明HSD可能对近端小管细胞有直接影响。此外，肾小管间质损伤与促炎和促纤维化表型有关，Th1和Th17表型增加，Tregs减少，随后IL-6，-17，-10，TNF-α，IFN-α增加。 γ和TGF-β。我们的结果揭示了一个复杂的网络，与HSD引起的肾损伤无关，而与血压的变化无关。这些发现加强了限制盐摄入量对普通人群甚至抗盐个体的重要性。