Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease

Abstract

Hypogonadism or testosterone deficiency is a prevalent condition in men with chronic kidney disease (CKD). Testosterone stimulates erythropoiesis via production of haematopoietic growth factors and possible improvement of iron bioavailability. We hypothesized that testosterone deficiency predisposes to anaemia and reduced responsiveness to erythropoiesis-stimulating agents (ESAs) in CKD men. Materials and methods. We studied associations between endogenous testosterone and haemoglobin in 239 ESA-naïve nondialysed CKD Stages 1-5 male patients. Additionally, we studied associations between endogenous testosterone levels and ESA dose (U/kg/week) in 126 ESA-treated men undergoing haemodialysis (HD). Among ESA-naïve males, patients with anaemia presented lower testosterone values. Endogenous testosterone was negatively associated with haemoglobin levels in uni- and multivariate models. Testosterone-deficient patients (total testosterone <10 nmol/L) were 5.3 (95% confidence interval 2.2-12.5) times more likely to be anaemic (Hb < 13.0 g/dL) than testosterone-sufficient patients. In ESA-treated men undergoing HD, higher ESA doses (above the median value of 121 IU/kg body weight/week) are associated with lower testosterone levels and higher percentage of hypochromic red blood cells (RBC). The inverse association between testosterone levels and ESA doses persisted after multivariate adjustment for age, sex hormone-binding globulin, comorbidities, C-reactive protein and s-albumin but was lost after further adjustment for iron medication and hypochromic RBC. Hypogonadism may be an additional cause of anaemia and reduced ESA responsiveness in men with CKD. Our results raise the possibility that restoration of testosterone levels in hypogonadal CKD males may translate into lower prevalence of anaemia and better ESA responsiveness.