Low Testosterone Level and Risk of Adverse Clinical Events among Male Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Cohort Studies

Abstract

The phenomenon of low testosterone level is extremely common in male patients with chronic kidney diseases (CKDs). This meta-analysis aimed to evaluate whether the low circulating testosterone could independently predict adverse outcomes among male patients with chronic kidney diseases (CKDs). The data till May 2022 were systematically searched from Pubmed, Web of Science, and Embase from inception. Studies meeting the PICOS (population, intervention/exposure, control/comparison, outcomes, and study design) principles were included in this meta-analysis. Study-specific effect estimates were pooled using fixed-effects (I2 > 50%) or random-effects models (I2 < 50%). Ultimately, 9 cohort studies covering 5331 patients with CKDs were involved in this meta-analysis. The results suggested that per 1-standard deviation (SD) decrease in total testosterone independently increased the risk of all-cause mortality by 27% [hazard risk (HR) 1.27, 95% confidence interval (CI) 1.16–1.38], cardiovascular mortality by 100% (HR 2.00, 95% CI 1.39–2.86), cardiovascular events by 20% (HR 1.20, 95% CI 1.04–1.39), and infectious events by 41% (HR 1.41, 95% CI 1.08–1.84). Besides, with per 1-SD decrease in free testosterone, the risk of overall adverse events increased by 66% (HR 1.66, 95% CI 1.34–2.05). Stratified analyses indicated that the negative relationship of the total testosterone with all-cause death risk was independent of factors involving age, race, body mass index, diabetes, hypertension, C-reactive protein, creatinine, and sex hormone binding globulin. In conclusion, it was identified that low endogenous testosterone could serve as an independent predictor of adverse clinical events among male patients with CKDs.

Understanding human aging and the fundamental cell signaling link in age-related diseases: the middle-aging hypovascularity hypoxia hypothesis

“…Hypoxia in chronic kidney disease ( Faivre et al, 2021 ; Wang B. et al, 2022 ) has been well studied and is used here to highlight the middle-aged (>50 years) ( Ryu et al, 2019 ) hypovascularity ( Fine and Norman, 2008 ; Evans et al, 2020 ; Querfeld et al, 2020 ) hypoxia ( Faivre et al, 2021 ; Wang L. et al, 2022 ) pathological trajectories in linking the endocrine system ( Zhao and Schooling, 2020 ; Li L. et al, 2022 ; Romejko et al, 2022 ), nitric oxide signaling, and oxygen homeostasis pathophysiology ( Burmakin et al, 2021 ; Carlström, 2021 ; Xu M. et al, 2022 ; Edwards and Kurtcuoglu, 2022 ). Oxidative stress–inflammation pathophysiology ( Ebert et al, 2021 ), amyloidosis ( Ryu et al, 2019 ; Herrera, 2021 ; Gurung and Li, 2022 ), autophagy ( Tang et al, 2020 ), and EMT ( Chen et al, 2022b ) would result in degenerative hypertrophy, fibrosis, atrophy, and neoplasm ( Ryu et al, 2019 ; Pinto et al, 2021 ) comorbid conditions ( Charles and Ferris, 2020 ).…”