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±32.45ml/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.