Introduction. Kidney transplantation is the preferred treatment for end-stage renal disease as it improves survival rates and quality of life. Yet, it may also sustain or initiation clinical complications such as hypogonadism. The hypothalamic-pituitary-gonadal axis(HPG-axis) is easily affected and it currently remains unclear whether HPG-axis dysfunction is present after kidney transplantation. Therefore, we aimed to investigate the HPG-axis in male kidney transplant recipients(KTR) and compared the analytical performance of the two different types of testosterone assays in this population.

Methods. We conducted a cross-sectional analysis including 337 adult male KTR with a functioning graft ≥1 year posttransplantation and 119 healthy male subjects from the general population as control group. Total plasma testosterone was measured in morning samples using both immunoassay and liquid chromatography tandem mass spectrometry(LC-MS/MS). Differences between KTR and controls were assessed with Mann-Whitney U tests. Passing Bablok regression was used to compare the two assays. The 2.5^th and 97.5^th percentiles were calculated to ascertain reference intervals.

Results. In total, 52% of the male KTR were deemed to have hypogonadism based on biochemical reference values of the control group. Male KTR had lower dihydrotestosterone (0.88 (0.63–1.25) vs. 1.77 (1.39–2.23);P<0.001) and testosterone levels (11.17 (8.98–15.15) vs. 19.51 (16.14–23.63);P<0.001) compared to healthy controls with the LC-MS/MS assay. Passing Bablok regression showed a R² of 0.71 with a proportional (β1 1.09 (1.03–1.16)) and systematic bias (β0 -1.08 (-1.97–-0.44)) between the immunoassay and LC-MS/MS testosterone assay.

Conclusion. Hypogonadism is frequently present in KTR when using general population based reference values. Especially in KTR, LC-MS/MS should be used instead of the immunoassay as the latter overestimates testosterone values in male KTR. Lastly, we present population specific mass spectrometry based reference values for androgens in male KTR to aid clinicians and future studies.