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Androgen Deficiency, Associations and Survival of Men With Stage 4 and 5 Chronic Kidney Disease: A Cohort Study
Neomal De Silva1, Richard Quinton1,2,3, Nipun Lakshitha De Silva3,4
1Department of Endocrinology & Metabolism, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Insights
Androgen deficiency (AD) is common in men with chronic kidney disease (CKD), affecting over two-thirds of patients. While low testosterone is linked to worse survival, further research is needed to confirm causation and explore treatment.
Area of Science:
- Nephrology
- Endocrinology
- Geriatrics
Background:
- Anaemia is a significant complication in chronic kidney disease (CKD).
- Androgen deficiency (AD) may contribute to anaemia in men, including those with CKD.
Purpose of the Study:
- To determine the prevalence of AD in male CKD patients.
- To assess the contribution of AD to anaemia in this population.
- To investigate the association between AD and long-term survival.
Main Methods:
- Cross-sectional observational study of 322 males aged 18+ with CKD stages 4-5.
- Analysis of blood samples for testosterone (T), free testosterone, and other biomarkers.
- Mortality data collected 15 years post-sampling for survival analysis.
Main Results:
- Prevalence of AD was 68.9% in the study cohort.
- Negative correlation between erythropoiesis-stimulating agent (ESA) dose and testosterone levels.
- Positive correlation between hemoglobin (Hb) and free testosterone in patients not on ESA therapy.
- AD significantly associated with worse survival (log-rank p < 0.001), but free testosterone was not independently associated in Cox regression.
Conclusions:
- AD is highly prevalent in men with advanced CKD, increasing with age and disease severity.
- Lower Hb and higher ESA doses associated with lower testosterone may be causative factors.
- Lower survival in men with low testosterone likely reflects overall poor health, not direct causation.
- Randomized controlled trials are needed to evaluate testosterone replacement therapy in men with CKD and AD.
Objectives:
Anaemia is a key cause of morbidity in chronic kidney disease (CKD). Androgen deficiency (AD) in males can contribute to anaemia of all causes, including in CKD. We sought to examine the prevalence of AD in men with CKD, the extent to which it contributed to anaemia and whether it was independently associated with long-term survival.
Methods:
This cross-sectional observational study was conducted among males aged 18 years and over with CKD stages 4 and 5. The study analysed morning blood samples with regard to their full blood count, urea and electrolytes, albumin, lipids, testosterone (T) and sex hormone binding globulin, with calculation of free testosterone by mass action equation. Mortality data were obtained 15 years later for survival analysis.
Results:
Among 322 patients with a mean age of 63 years, the overall prevalence of AD was 68.9%. There was a statistically significant negative correlation between erythropoiesis stimulating agent (ESA) dose and testosterone concentrations (Pearson correlation -0.193, p = 0.05). There was a positive correlation between haemoglobin (Hb) and free testosterone level among patients not on ESA therapy (Pearson correlation 0.331, p < 0.001). Kaplan-Meier plots showed p < 0.001 on log-rank analysis, indicating that AD was significantly associated with worse survival. However, in Cox regression analysis, free testosterone was not associated with survival (95% CI for free testosterone 0.997-1.000).
Conclusions:
AD is highly prevalent among this population, and increases further with older age and more severe CKD warranting haemodialysis. Association of lower Hb and higher ESA dose with lower T concentration might be causative, which has important pharmaco-economic as well as clinical implications. Lower survival in men with low T, more likely reflects overall poor health rather than causation. A properly constituted randomised controlled study evaluating the effect of native T replacement is warranted in men with CKD and AD.
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