Testosterone deficiency is common in many patients with chronic kidney disease (CKD), but the treatment of this deficiency and associated side effects have not always received much attention.
The prevalence of CKD patients with low testosterone is estimated at 50%-70%. Testosterone has effects on hemoglobin levels as well as lean body mass accrual. Several recent studies have elucidated more connections between testosterone and pertinent clinical parameters.
Using data from the Study of Health in Pomerania (SHIP), German investigators reviewed the overall associations between testosterone level in CKD patients and mortality risk (Am J Nephrol 2011;33:209-217).
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The total cohort included 1,822 men with a median age of 51 years and median estimated glomerular filtration rate (eGFR) of 83.2 mL/min/1.73 m2. Of the entire cohort, 6.4%, 19.1%, and 22.8% had kidney dysfunction, albuminuria, and CKD, respectively. Testosterone levels were significantly lower in groups with kidney dysfunction, albuminuria, and CKD.
After multivariate adjustment, these three groups also exhibited significantly shorter survival time. Kidney dysfunction, albuminuria, and CKD were associated with a 40%, 38%, and 42% increased risk of all-cause mortality, respectively. These associations were much stronger in patients aged 29-69, in whom kidney dysfunction was associated with a twofold increased risk of all-cause mortality, and albuminuria and CKD were associated with a 62% and 66% increased risk, respectively. Additionally, kidney dysfunction was associated with a 2.0 and 4.3 times increased risk for cardiovascular mortality in the entire cohort and the 29-69 age group.
Excluding first-year deaths, significant associations were still seen in all-cause mortality in the albuminuria and CKD groups, whereas only cardiovascular mortality was significantly associated with kidney dysfunction. Patients with kidney dysfunction, albuminuria, or CKD had shorter survival when they also had low total testosterone. In subjects with low total testosterone, kidney dysfunction was associated with a 2.5 times increased risk of all-cause mortality in the entire cohort and a 17 times increased risk in the 29-69 age group.
Another group of investigators aimed to find associations between anemia, resistance to erythropoiesis-stimulating agents (ESAs), and testosterone levels (Nephrol Dial Transplant 2012;27:709-715).
The study enrolled 239 patients with a median eGFR of 48 and median age of 53. Twenty-three percent of the cohort had anemia, and these patients were significantly more likely to have a reduced eGFR and testosterone level, have an elevated C-reactive protein (CRP) and parathyroidim hormone (PTH) levels, and diabetes.
In multivariate analysis controlling for age, body mass index (BMI), diabetes status, cardiovascular disease, albumin, PTH, CRP, and eGFR, the researchers found a significant association between hemoglobin and testosterone. Anemia was five times more likely to be found in testosterone-deficient patients. Of the patients taking ESAs, testosterone was negatively associated with ESA dosage in multivariate analysis.
This relationship, however, did not remain significant when adjusting for hypochromic red blood cells. Of note, ESA dose was also significantly associated with BMI, but the multivariate model testing for associations between testosterone and ESA dose did not control for BMI.
