α-Klotho gene and protein measurements in humans and their role as a clinical biomarker of disease

Alpha-Klotho (α-Klotho) was serendipitously discovered as a suppressor of premature organ failure, which resembles premature aging. Animal experiments and human observational studies indicate that α-Klotho deficiency is associated with a wide spectrum of diseases, and α-Klotho is a promising biomarker for both early detection and prediction of outcome in human kidney disease. Moreover, preclinical data support that α-Klotho deficiency is not only a biomarker but also a pathogenic factor for kidney and nonkidney diseases. Therefore, strategies to increase circulating α-Klotho could prevent or treat certain diseases. In this chapter, we discuss different α-Klotho measurements in humans and rodents and summarize evolving preclinical data supporting the potential therapeutic application of α-Klotho although no human clinical trials have been yet conducted. Finally, we briefly discuss the potential challenges and opportunities to target α-Klotho for the diagnosis and treatment of human diseases, with emphasis in kidney disease.