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Endogenous urinary glucocorticoid metabolites and mortality in prednisolone-treated renal transplant recipients
Annet Vulto1, Isidor Minović1,2,3, Laura V de Vries1
1Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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.
Insights
Chronic corticosteroid use in renal transplant recipients alters endogenous glucocorticoid production and 11β-hydroxysteroid dehydrogenase (11β-HSD) activity. Lower metabolite excretion and higher 11β-HSD activity correlate with increased mortality risk.
Area of Science:
- Endocrinology
- Nephrology
- Pharmacology
Background:
- Chronic corticosteroid therapy, like prednisolone, can suppress the hypothalamic-pituitary-adrenal (HPA) axis.
- Corticosteroids may also affect the activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) enzymes.
- Investigating these alterations is crucial for understanding long-term outcomes in transplant patients.
Purpose of the Study:
- To compare endogenous glucocorticoid production and 11β-HSD activity in prednisolone-treated renal transplant recipients (RTR) versus healthy controls.
- To determine if these altered activities impact the long-term survival of RTR.
Main Methods:
- A longitudinal cohort study involving 693 stable RTR and 275 healthy controls.
- Measurement of 24-hour urinary cortisol, cortisone, THF, alloTHF, and THE using liquid chromatography-tandem-mass spectrometry.
- Calculation of endogenous glucocorticoid production and 11β-HSD activity using urinary metabolite ratios.
Main Results:
- RTR exhibited significantly lower urinary cortisol and metabolite excretion compared to controls (P < .001).
- RTR showed significantly higher (THF + alloTHF)/THE and cortisol/cortisone ratios (P < .001 and P = .002, respectively), indicating altered 11β-HSD activity.
- Lower metabolite excretion and higher (THF + alloTHF)/THE ratios were independently associated with an increased risk of mortality.
Conclusions:
- Prednisolone treatment in RTR alters endogenous glucocorticoid production and 11β-HSD enzyme activity.
- Reduced urinary glucocorticoid metabolite excretion and increased (THF + alloTHF)/THE ratios are significant predictors of mortality in RTR.
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