Rapid decline of kidney function in diabetic kidney disease is associated with high soluble Klotho levels

Background: Klotho is found in two forms: a transmembrane form and a soluble form (s-Klotho). In order to be excreted, s-Klotho, that is too large to be filtered, will probably reach the proximal convoluted tubule by a transcytosis process. The aim of our study was to show the relationship between the levels of s-Klotho and tubular injury in patients with diabetic kidney disease (DKD), using as tubular injury marker the kidney injury molecule-1 (KIM-1). Methods: Our study included 63 DKD patients (stages 1-5, mean eGFR 65.15 +/- 32.45 ml/min) with a mean age 58.13 +/- 12 years. In all patients we determined serum levels of: KIM-1 and s-Klotho using ELISA, urinary albumin/creatinine ratio (UACR) and reduction in the estimated glomerular filtration rate (eGFR) per year. Results: We found a strong statistically significant correlation of s-Klotho with the rate of reduction of eGFR/year (r = 0.714, p = 0.0004) and with the tubular injury marker KIM-1 (r = 0.758, p = 0.005) and strong correlations of UACR with the rate of reduction of eGFR/year (r = 0.53, p < 0.01), KIM-1 (r = 0.49, p < 0.05) and s-Klotho (r = 0.52, p < 0.01). Conclusion: Despite previous published data, that shows a decrease of s-Klotho in chronic kidney disease, in our study the rapid annual decline of kidney function but not the level of eGFR was associated with increased s-Klotho. A possible explanation could be a more severe proximal tubule injury that could lead to a reduction of tubular excretion of s-Klotho as suggested by the correlation of s-Klotho levels with the serum levels of KIM-1. (C) 2018 Sociedad Espanola de Nefrologia. Published by Elsevier Espana, S.L.U.