Endogenous urinary glucocorticoid metabolites and mortality in prednisolone‐treated renal transplant recipients

BACKGROUND: Chronic corticosteroid treatment suppresses HPA‐axis activity and might alter activity of 11β hydroxysteroid dehydrogenases (11β‐HSD). We aimed to investigate whether the endogenous glucocorticoid production and 11β‐HSD activities are altered in prednisolone‐treated renal transplant recipients (RTR) compared with healthy controls and whether this has implications for long‐term survival in RTR. METHODS: In a longitudinal cohort of 693 stable RTR and 275 healthy controls, 24‐hour urinary cortisol, cortisone, tetrahydrocorisol (THF), allotetrahydrocortisol (alloTHF), and tetrahydrocortisone (THE) were measured using liquid chromatography tandem‐mass spectrometry. Twenty‐four‐hour urinary excretion of cortisol and metabolites were used as measures of endogenous glucocorticoid production; (THF + alloTHF)/THE and cortisol/cortisone ratios were used as measures of 11β‐HSD activity. RESULTS: Urinary cortisol and metabolite excretion were significantly lower in RTR compared with healthy controls (P < .001), whereas (THF + alloTHF)/THE and cortisol/cortisone ratios were significantly higher (P < .001 and P = .002). Lower total urinary metabolite excretion and higher urinary (THF + alloTHF)/THE ratios were associated with increased risk of mortality, independent of age, sex, estimated glomerular filtration rate, C‐reactive protein, body surface area, and daily prednisolone dose, respectively. CONCLUSIONS: Endogenous glucocorticoid production and 11β‐HSD activities are altered in prednisolone‐treated RTR. Decreased total urinary endogenous glucocorticoid metabolite excretion and increased urinary (THF + alloTHF)/THE ratios are associated with increased risk of mortality.