Association between Serum Soluble α-Klotho and Urinary Albumin Excretion in Middle-Aged and Older US Adults: NHANES 2007-2016

(1) Background: Preclinical and clinical studies on the anti-aging effect of alpha-Klotho are emerging. Urinary albumin excretion (UAE) is a well-known biomarker of kidney injury and generalized damage in the cardiovascular system. However, the potential relationship between alpha-Klotho and UAE is limited and controversial. This study aimed to quantify this relationship in the general middle-aged and elderly population from the National Health and Nutrition Survey (NHANES) 2007-2016. (2) Methods: Serum alpha-Klotho was measured by enzyme-linked immunosorbent assay. UAE was assessed by the albumin-to-creatinine ratio (ACR). After adjusting for several confounding variables, the relationship between alpha-Klotho and ACR was analyzed by weighted multivariable logistic regression, subgroup analysis, and interaction tests. A generalized additive model (GAM) with smooth functions using the two-piecewise linear regression model was used to examine the potential nonlinear relationship between alpha-Klotho and ACR. (3) Results: Among 13,584 participants aged 40-79 years, we observed an independent and significant negative correlation between alpha-Klotho and ACR (beta = -12.22; 95% CI, -23.91, -0.53, p = 0.0448) by multivariable logistic regression analysis, especially in those with age >= 60 years, pulse pressure (PP) >= 60 mmHg, hypertension or diabetes. We further discovered the nonlinear relationship between alpha-Klotho and ACR by GAM, revealing the first negative and then positive correlations with an inflection point of 9.91 pg/mL between alpha-Klotho and ACR. (4) Conclusions: A dose-response relationship between alpha-Klotho and ACR was demonstrated, and the negative correlation therein indicated that alpha-Klotho has potential as a serum marker and prophylactic or therapeutic agent despite its metabolic and effective mechanisms needing to be further explored.