Effects of salt intake on kidney transplant recipients to protect renal function from calcineurin inhibitor nephrotoxicity

Tonicity-responsive enhancer binding protein (TonEBP) protects kidney tubular cells against hypertonicity. Calcineurin inhibitors (CNI) are known to suppress TonEBP by hampering nuclear translocation. Moreover, sodium inversely activates TonEBP. We investigated whether CNI-induced nephrotoxicity in transplant recipients could be due to impaired TonEBP activity, and whether sodium restriction exacerbates the intoxication. Immunohistochemical analysis using biopsy specimens from 128 patients revealed that TonEBP was mainly located in the cytoplasm in cases of CNI nephrotoxicity, while it showed nuclear-cytoplasmic staining in cases of rejection or interstitial fibrosis and tubular atrophy. This suggests that TonEBP transactivation is limited in CNI nephrotoxicity. A retrospective observational analysis of 308 kidney transplant recipients at our institute between 1984 and 2018 showed a positive correlation between dietary salt intake and eGFR slope.A low-salt diet is linked to a rapid annual decline in eGFR, with adjusted odds ratios of 2.40 and a 95% confidence interval of 1.18-4.90. These findings suggest that the recommended salt intake for kidney transplant recipients may require reassessment.