Endocrine Abstracts

Background: The kidneys are central to steroid hormone action, serving both as a target organ for steroid signalling and a key regulator of steroid metabolism. In chronic kidney disease (CKD), impaired enzymatic activity, dysregulated feedback loops, and reduced renal clearance disrupt these pathways, contributing to metabolic complications. While previous studies have identified specific disturbances in steroid metabolism in CKD, an integrated understanding of altered steroid profile is limited.

Aim: To characterise the adrenal steroid profile in chronic kidney disease in a comprehensive and integrated fashion.

Methods: A case-control study recruited 17 patients with CKD (pre-dialysis CKD stage 4-5) and 14 healthy volunteers, matched for age, sex and BMI. Liquid chromatography–mass spectrometry quantified progestogens, glucocorticoids, mineralocorticoids, androgens and their metabolites in 8am fasting serum (19 analytes) and 24-hour urine (29 analytes). Comparisons used Mann–Whitney U with Benjamini Hochberg correction (FDR 0.05). Exploratory analyses examined associations with skeletal muscle function (gait, chair-rise speed) and inflammation (CRP, TNFα).

Results: Mean participant age was 70.7±5.1years, and 42% were female. CKD participants showed broad steroidogenic disruption. Serum levels in CKD were reduced for cortisone, 11-oxygenated androgens (11KT, 11OHT) and DHEA. Urine steroid amount in CKD was reduced for cortisone and its metabolites (THE, α-cortolone, β-cortolone), corticosterone metabolites (THA, 5αTHA, THB) and progestogen metabolites (5PT, PD, 5PD). Using urinary steroid ratios as surrogate markers, enzymatic activity appeared decreased for 11βHSD2 and increased for 3βHSD2. Better physical performance in CKD is associated with higher serum THF, 5αTHF and THE, and lower TNFα.

Conclusion: CKD is associated with multi-pathway disruption of steroid metabolism. Observations are consistent with previously reported alterations in 11β-HSD metabolism, but additionally reveal novel shifts suggesting increased 3β-HSD activity and other unexplained changes in adrenal steroid profiles. Further mechanistic and longitudinal studies are warranted to clarify underlying mechanisms and clinical implications.