Endogenous Glucocorticoid Metabolites and Mortality in Prednisolone-Treated Renal Transplant Recipients

L.V. de Vries, A.C. Timmermans, I. Minovic, M. van Faassen, A.W. Gomes Neto, D.J. Touw, M.F.C. de Jong, A.P. van Beek, R.P.F. Dullaart, G.J. Navis, I.P. Kema, S.J.L. Bakker

Thursday 15 march 2018

15:35 - 15:40h at Willem Burger Foyer

Categories: Clinical, Session (poster)

Parallel session: Poster session 2: Clinical

Background

he majority of renal transplant recipients (RTR) are still treated with corticosteroids, but there is currently no way to guide intensity of treatment. Chronic corticosteroid treatment suppresses the hypothalamus-pituitary-adrenal (HPA)-axis and might alter activity of 11-beta hydroxysteroid dehydrogenases (11β-HSD). We aimed to investigate whether HPA-axis and 11β-HSD activities are altered in prednisolone-treated RTR compared to healthy controls and whether this has implications for long-term survival in RTR.

Methods

In a longitudinal cohort of 693 stable prednisolone-treated RTR (aged 53±13 years, 57% male, median [IQR] follow-up 5.3 [4.7-6.1] years) and 275 age-matched healthy controls (aged 53±11 years, 48% male), baseline total urinary cortisol, cortisone, tetrahydrocortisol (THF), allo-tetrahydrocortisol (alloTHF), and tetrahydrocortisone (THE) were measured using LC-MS/MS. Twenty-four hour total urinary cortisol excretion and summated cortisol and metabolite (=cortisol+cortisone+THF+alloTHF+THE) excretion were used as measures of HPA-axis activity; (THF+alloTHF)/THE and cortisol/cortisone ratios were used as estimates of 11β-HSD activity.

Results

Total urinary cortisol excretion and summated cortisol and metabolite excretion were significantly lower in RTR compared with healthy controls (P

Conclusions

HPA-axis and 11β-HSD activities are altered in prednisolone-treated RTR, compared to healthy controls. Decreased urinary summated cortisol and metabolite excretion and increased urinary (THF+alloTHF)/THE ratio are independently associated with increased risk of mortality after kidney transplantation. Measuring endogenous glucocorticoid metabolites might prove to be a future tool to guide personalized corticosteroid therapy.