Case-control and longitudinal study of sex steroids in male patients with chronic kidney disease before and after kidney transplantation

Abstract Introduction Sex steroids in male patients decrease along the progression of chronic kidney disease (CKD), and associate with worse outcome. This study aimed to increase the knowledge of the pathophysiology of biochemical hypogonadism in male CKD and reversibility after kidney transplantation. Methods We comprehensively mapped the hypothalamic-pituitary-gonadal (HPG) axis in 120 male patients (age 65y, BMI 26.8 kg/m²) with CKD stage 1-5, and 120 kidney-healthy controls, matched (1:1) for age and BMI. We furthermore monitored the HPG axis in 50 male kidney transplant recipients (age 60y) from time of transplantation up to 12 months. Testosterone (T) was measured by liquid chromatography tandem mass-spectrometry. Luteinizing hormone (LH), follicle stimulating hormone (FSH), and inhibin B levels were assessed by immunoassay. T/LH ratio and inhibin B/FSH ratio served as a proxy for Leydig and Sertoli cell function, respectively. Results Hypogonadism is prevalent in CKD, and characterized by depressed T/LH ratio (1.75[0.71-2.96] vs 3.99[2.39-5.20], p<0.0001) and inhibin B/FSH ratio (14.40[1.24-33.64] vs 32.24[16.27-56.72], p<0.0001). T levels showed a steady increase shortly after transplantation, while LH levels decreased, resulting in a higher T/LH ratio (p<0.0001). Inhibin B levels, decreased after 3 months, resulting in a lower inhibin B/FSH ratio after 3 months (p<0.0001), with partial recovery after 12 months. Conclusions Male CKD patients showed low T/LH and inhibin B/FSH ratios pointing towards testicular failure as underlying pathophysiological mechanism. Male CKD can be considered a state of premature testicular ageing. Leydig cell function rapidly recovered after kidney transplantation suggesting a functional cause of CKD-induced hypogonadism. Sertoli cell function, conversely, showed a deterioration, especially in the early post-transplant period.