Case-Control and Longitudinal Study of Sex Steroids in Male Patients with CKD Before and After Kidney Transplantation.

INTRODUCTION

Sex steroids in male patients decrease along with the progression of chronic kidney disease (CKD) and are associated with worse outcomes. This study aimed to increase the knowledge of the pathophysiology of biochemical hypogonadism in male CKD and its reversibility after kidney transplantation (KT).

METHODS

We comprehensively mapped the hypothalamic-pituitary-gonadal (HPG) axis in 120 male patients (age 65 yrs, body mass index [BMI]: 26.8 kg/m2) with CKD stage 1 to 5, and 120 kidney-healthy controls, matched (1:1) for age and BMI. Additionally, we monitored the HPG axis in 50 male kidney transplant recipients (age 60 yrs) from the 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 the function of Leydig and Sertoli cells, respectively.

RESULTS

Hypogonadism is prevalent in CKD and is 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, whereas 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.

CONCLUSION

Male patients with CKD 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 KT suggesting a functional cause of CKD-induced hypogonadism. In contrast, Sertoli cell function showed a deterioration, especially in the early post-transplant period.