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Serum testosterone levels and mortality in men with CKD stages 3-4
Kiranpreet K Khurana1, Sankar D Navaneethan2, Susana Arrigain3
1Department of Urology, Glickman Urological & Kidney Institute, Cleveland, OH.
Insights
Low testosterone levels (hypogonadism) in men with chronic kidney disease (CKD) stages 3-4 may be linked to increased mortality risk. Further research is needed to confirm this association in CKD patients.
Area of Science:
- Nephrology
- Endocrinology
- Cardiovascular Medicine
Background:
- Hypogonadism (total testosterone <350 ng/dL) is linked to increased cardiovascular disease and mortality risk in men undergoing dialysis.
- The association between hypogonadism and mortality in men with non-dialysis-dependent chronic kidney disease (CKD) requires further investigation.
Purpose of the Study:
- To evaluate the association between hypogonadism and all-cause mortality in men with CKD stages 3-4.
- To identify factors associated with hypogonadism in this patient population.
Main Methods:
- Retrospective cohort study of 2,419 men with CKD stages 3-4 (eGFR 15-59 mL/min/1.73 m2).
- Total testosterone levels were measured using immunoassay and analyzed as categorized (low/normal/TRT), continuous log, and quintiles.
- Logistic regression and Cox proportional hazard models were used to assess associations with hypogonadism and mortality.
Main Results:
- 53% of men (1,288/2,419) had hypogonadism. African American ethnicity, higher eGFR, diabetes, and higher BMI were associated with hypogonadism.
- During a median follow-up of 2.3 years, 15% of patients (357/2,419) died.
- Low testosterone (<350 ng/dL) or testosterone replacement therapy was not associated with mortality. However, higher log testosterone was associated with lower mortality (HR 0.70), and the second lowest quintile was associated with higher mortality (HR 1.53) compared to the highest.
Conclusions:
- Low total testosterone levels may be associated with increased mortality in men with CKD stages 3-4.
- Limitations include single-center design, timing of testosterone testing, and lack of adjustment for proteinuria.
- Further research is warranted to clarify the relationship between testosterone levels and mortality in CKD patients.
Background:
Hypogonadism in men (total testosterone <350 ng/dL) is associated with higher risk of cardiovascular disease and mortality in men on dialysis therapy. We evaluated the association of hypogonadism with all-cause mortality in men with non-dialysis-dependent chronic kidney disease (CKD).
Study Design:
Retrospective, cohort study.
Setting & Participants:
2,419 men with CKD stages 3-4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total testosterone measured for cause between January 1, 2005, and October 31, 2011, at a tertiary-care center in Cleveland, OH.
Predictors:
Total testosterone measured using an immunoassay measurement in 3 forms: (1) categorized as low or testosterone replacement therapy versus normal, (2) continuous log testosterone, and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL).
Outcomes:
Factors associated with low total testosterone level and the association between low total testosterone level and all-cause mortality were evaluated using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves.
Results:
Hypogonadism was found in 1,288 of 2,419 (53%) men. In a multivariable logistic regression analysis, African American ethnicity and higher estimated glomerular filtration rate were associated with lower odds of having hypogonadism. Diabetes and higher body mass index were associated with higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a median follow-up of 2.3 years. In the multivariate Cox model, testosterone level <350 ng/dL or testosterone replacement therapy was not associated with mortality. In a multivariable model also adjusted for testosterone supplementation, higher log testosterone was associated with significantly lower mortality (HR per 1 log unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second lowest quintile of testosterone was associated with higher mortality (HR, 1.53; 95% CI, 1.09-2.16).
Limitations:
Single-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias.
Conclusions:
Low total testosterone level may be associated with higher mortality in men with CKD stages 3-4, but more studies are needed.
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