Twenty-four hour urinary cortisol excretion and the metabolic syndrome in prednisolone-treated renal transplant recipients

- Chronic prednisolone treatment after kidney transplantation suppresses the HPA-axis.
- Considerable inter-individual variation exists in the degree of HPA-axis suppression.
- The degree of HPA-axis suppression is associated with metabolic syndrome prevalence.
- The degree of HPA-axis suppression is associated with metabolic abnormalities.
- LC-MS/MS accurately measures urinary cortisol in patients treated with prednisolone.

Chronic prednisolone treatment in renal transplant recipients (RTR) causes metabolic abnormalities, which cluster in the metabolic syndrome (MS). It also suppresses the hypothalamic-pituitaryadrenal (HPA)-axis. We investigated whether HPA-axis suppression, as measured by 24 h urinary cortisol excretion, is associated with presence of the MS and its individual components, in outpatient RTR with a functioning graft for >1 year. Urinary cortisol was measured in 24 h urine, using LC-MS/MS (LOQ 0.30 nmol/L). We included 563 RTR (age 51 ± 12 years; 54% male) at median 6.0 [IQR, 2.6-11.5] years post-transplantation. MS was present in 439/563 RTR (78%). Median 24 h urinary cortisol excretion was 2.0 [IQR, 0.9-5.1] nmol/24 h. Twenty-four hour urinary cortisol excretion was independently associated with MS presence (OR = 0.80 [95% CI, 0.66-0.98], P = 0.02). It was also independently associated with bodyweight (st.β = −0.11, P = 0.007), waist circumference (st.β = −0.10, P = 0.01), BMI (st.β = −0.14, P = 0.001), fasting triglycerides (st.β = −0.15, P = 0.001), diabetes (st.β = −0.12, P = 0.005), and number of antihypertensives used (st.β = −0.13, P = 0.003). Suppressed HPA-axis activity, as reflected by decreased 24 h urinary cortisol excretion, is associated with higher prevalence of MS and its individual components (i.e. central obesity, dyslipidemia, diabetes, hypertension) in prednisolone-treated RTR. Assessment of 24 h urinary cortisol excretion by LC-MS/MS may be a tool to monitor metabolic side-effects of prednisolone in RTR.