Dataset Information

The role of serum testosterone and dehydroepiandrosterone sulfate in kidney function and clinical outcomes in chronic kidney disease: a systematic review and meta-analysis.

ABSTRACT:

Objective/design

Testosterone might mediate sex differences in kidney function and chronic kidney disease (CKD). However, the few studies analyzing the association between testosterone and kidney function showed conflicting results. Therefore, we performed a systematic review and meta-analysis.

Methods

Six electronic databases were searched from inception to March 4th, 2020 for studies that investigated the association of 1) testosterone status with kidney function in the general population, or: 2) testosterone status with clinical outcomes (kidney function decline, kidney failure, cardiovascular (CV) events, and cardiovascular and all-cause mortality) in CKD patients. We used random and fixed effect models to obtain pooled effect estimates with 95% confidence intervals (CI).

Results

No randomized controlled trials that met the inclusion criteria were identified. One study was conducted in the general population and reported an increased risk of incident CKD with low vs. normal testosterone (hazard ratio (HR) 1.38, 95%CI 1.05;1.80). Seven studies were conducted in men with CKD and included testosterone as determinant, of which six could be meta-analyzed. Low testosterone was associated with an increased risk of all-cause mortality and CV events (pooled HR 1.98, 95%CI 1.36;2.89; pooled HR of 2.40 (95%CI 1.22;4.71), respectively). Two studies showed an increased risk of all-cause mortality with decreased dehydroepiandrosterone sulfate (DHEAS) in men with CKD; results regarding CV events were conflicting.

Conclusions

Although literature is scarce, evidence suggests that lower testosterone may increase CKD risk in the general population and risk of all-cause mortality and CV events in men with CKD. Whether testosterone supplementation could prevent these potential detrimental outcomes should be determined in future intervention studies.

SUBMITTER: van der Burgh AC

PROVIDER: S-EPMC9254301 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChronic kidney disease (CKD) has an apparent sex disparity, with a more rapid progress in men than in women. Whether the well-established sex-specific evolutionary biology trade-off between reproduction and longevity might inform CKD has not previously been considered. Relevant evidence from randomized controlled trials (RCTs) is not available.MethodsWe used a bi-directional Mendelian randomization study to obtain unconfounded estimates using the UK Biobank. Single nucleotide polymorphisms (SNPs) that strongly (p value < 5 × 10-8) predicted testosterone in a sex-specific manner were applied to 179,916 white British men (6016 CKD cases) and 212,079 white British women (5958 CKD cases) to obtain sex-specific associations with CKD, albuminuria, and estimated glomerular filtration rate (eGFR). We also used multivariable MR to control for sex hormone binding globulin (SHBG). For validation, we similarly examined their role in hemoglobin and high-density lipoprotein cholesterol (HDL-c). We also assessed the role of kidney function in serum testosterone, by applying eGFR-related SNPs to testosterone in the UK Biobank.ResultsGenetically predicted testosterone was associated with CKD in men (odds ratio (OR) for bioavailable testosterone 1.17 per standard deviation, 95% confidence interval (CI) 1.03 to 1.33) based on 125 SNPs but not in women (OR 1.02, 95% CI 0.92 to 1.14 for total testosterone) based on 254 SNPs. Multivariable MR allowing for SHBG showed consistent patterns. Genetically predicted bioavailable testosterone in men and women and genetically predicted total testosterone in women increased hemoglobin and lowered HDL-c, as seen in RCTs. Genetically predicted eGFR was not related to serum testosterone in men or in women.ConclusionsGenetically predicted testosterone was associated with CKD and worse kidney function in men, whilst not affected by kidney function. Identifying drivers of testosterone and the underlying pathways could provide new insights into CKD prevention and treatment.