Pathophysiologic Implications and Therapeutic Approach of Klotho in Chronic Kidney Disease: A Systematic Review

Abstract

The Klotho protein, known as an antiaging protein, is expressed mainly in the kidney, and kidney disorders may contribute to the disrupted expression of renal Klotho. The purpose of this systematic review was to determine if there are biological and nutraceutical therapies that increase the expression of Klotho and can help prevent complications associated with chronic kidney disease. A systematic literature review was carried out through the consultation of PubMed, Scopus, and Web of Science. Records between the years 2012 and 2022 in Spanish and English were selected. Cross-sectional or prevalence and analytical studies were included that evaluated the effects of Klotho therapy. A total of 22 studies were identified after the critical reading of these selected studies: 3 investigated the association between Klotho and growth factors, 2 evaluated the relationship between the concentration of Klotho and the type of fibrosis, 3 focused on the relationship between vascular calcifications and vitamin D, 2 assessed the relationship between Klotho and bicarbonate, 2 investigated the relationship between proteinuria and Klotho, 1 demonstrated the applicability of synthetic antibodies as a support for Klotho deficiency, 1 investigated Klotho hypermethylation as a renal biomarker, 2 investigated the relationship between proteinuria and Klotho, 4 linked Klotho as an early marker of chronic kidney disease, and 1 investigated Klotho levels in patients with autosomal dominant polycystic kidney disease. In conclusion, no study has addressed the comparison of these therapies in the context of their use with nutraceutical agents that raise the expression of Klotho.