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

Abstract

(1) Background: Preclinical and clinical studies on the anti-aging effect of α-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 α-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 α-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 α-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 α-Klotho and ACR. (3) Results: Among 13,584 participants aged 40–79 years, we observed an independent and significant negative correlation between α-Klotho and ACR (β = −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 α-Klotho and ACR by GAM, revealing the first negative and then positive correlations with an inflection point of 9.91 pg/mL between α-Klotho and ACR. (4) Conclusions: A dose-response relationship between α-Klotho and ACR was demonstrated, and the negative correlation therein indicated that α-Klotho has potential as a serum marker and prophylactic or therapeutic agent despite its metabolic and effective mechanisms needing to be further explored.

Urinary Excretion of Biomolecules Related to Cell Cycle, Proliferation, and Autophagy in Subjects with Type 2 Diabetes and Chronic Kidney Disease

“…The associations between low serum and urinary Klotho and albuminuria in patients with T2D were noted in previous studies [ 48 , 59 , 60 ]. Some experimental data may help explain the mechanism of this relationship.…”

Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism

“…Interestingly, when we analyzed the relationship between Klotho concentration and inflammatory biomarkers, lipid biomarkers and renal function biomarkers, we found that Klotho had a threshold effect in the same concentration range, suggesting that there was an optimal concentration range (around 1000 pg/ml) for Klotho to exert its biological function. A recent study found that all-cause mortality was lowest in the general population at Klotho concentrations around 1000 pg/ml (961.4 to 1140.0 pg/ml) [82]. These findings provided a basis for clinically monitoring Klotho concentration, but the precise concentration range required further investigation.…”

Thyroid function and thyroid homeostasis parameters are associated with increased urinary albumin excretion in euthyroid individuals over 60 years old from NHANES

“…Urinary albumin and creatinine levels were measured from a single spot urine sample utilizing solid-phase fluorescence immunoassay and a modified Jaffe kinetic method ( 12 ). The UACR was computed by dividing the concentration of urinary albumin (mg) by the concentration of urinary creatinine (g).…”

“…This phenomenon is frequently regarded as the most sensitive and dependable diagnostic marker for the early identification of chronic kidney disease (CKD) in cases where the estimated glomerular filtration rate (eGFR) is within the normal range. Furthermore, it is linked to unfavorable health outcomes ( 11 , 12 ). In addition, UAE has also been shown to be an independent predictor of CKD progression and cardiovascular risk ( 7 , 13 ).…”