High cortisol levels are associated with oxidative stress and mortality in maintenance hemodialysis patients

Abstract

Background Chronic stimulation of the mineralocorticoid receptor has been suggested as one of the potential causes of cardiovascular events and death in patients with end-stage renal disease. This observational cohort study was performed to demonstrate that serum cortisol might be a predictive marker for patient mortality and to evaluate its association with oxidized low-density lipoprotein (oxLDL) in hemodialysis (HD) patients. Methods Patients receiving HD three times a week were screened for enrollment at two institutions. Baseline cortisol levels were measured before each HD session, and the patients were divided into two groups according to the median value of serum cortisol before analysis. The baseline characteristics and laboratory values of the high and low cortisol groups were compared. Serum cortisol, adrenocorticotropic hormone, renin, aldosterone, and oxLDL were measured in 52 patients to evaluate the effect of oxidative stress on serum cortisol levels. Results A total of 133 HD patients were enrolled in this cohort study. Compared to the patients with low serum cortisol levels, the patients with high serum cortisol levels (baseline cortisol ≥ 10 μg/dL) showed higher rates of cardiovascular disease (59.7% vs. 39.4%, P=0.019) and left ventricular systolic dysfunction (LVSD) (25.9% vs. 8.0%, P=0.016). The patients in the high cortisol group demonstrated higher all-cause mortality than those in the low cortisol group. The serum cortisol level was an independent risk factor for patient mortality (hazard ratio 1.234, 95% confidence interval 1.022-1.49, P=0.029). Among the 52 patients with oxLDL measurements, oxLDL was an independent risk factor for elevated serum cortisol levels (Exp(B) 1.114, P=0.013) and LVSD (Exp(B) 12.308, P=0.045). However, plasma aldosterone levels did not affect serum cortisol levels. Conclusions Serum cortisol is a useful predictive marker for all-cause death among patients receiving HD. OxLDL is an independent marker for elevated serum cortisol among HD patients.

Cortisol excess in chronic kidney disease – A review of changes and impact on mortality

“…Cardiovascular disease prevalence was associated with morning serum cortisol levels in the report by Kim et al. ( 87 ), but not in the report by Gracia-Iguacel et al. ( 85 ).…”

“…( 50 ), no significant association with fasting glucose or diabetes prevalence was found in a dialysis cohort by Kim et al. ( 87 ). More research is needed to examine potential links between glycaemic control and more sensitive markers of systemic cortisol exposure in CKD.…”

“…( 84 ). One-off serum cortisol measurements were not correlated with hypertension in two cohorts of haemodialysis patients ( 85 , 87 ), but it is important to bear in mind the inherent limitations with this marker of cortisol exposure.…”

“…Mortality in relation to cortisol levels has been investigated specifically in adults with CKD in several studies ( Table 5 ). Morning cortisol was associated with adjusted all-cause mortality in two cohort studies of patients on haemodialysis ( 85 , 87 ). The largest cohort study to date, involving 1255 patients with diabetes on haemodialysis, reported increased crude hazard ratios for all-cause and cardiovascular mortality with higher morning cortisol.…”

Levels of Cortisol and Inflammatory Cytokines after The Induction of Various Sleep Deprivation Stress Models in Male Wistar Rats

“…Sleep recovery also decreases lipid peroxidase and free radical production by increasing glutathione and other enzymatic antioxidants (Hirotsu et al, 2015). Glutathione increases after sleep recovery for two days, indicated by the elevation of 6-PGD, an enzyme that acts on the pentose phosphate pathway in the carbohydrate metabolism that protects cells from oxidative stress in the form of NADPH, thus inhibiting stress oxidative that has a role in cortisol increase (Kim et al, 2022). Taken together, these results indicate that sleep recovery is able to decrease cortisol levels which increase after induction of PSD or TSD.…”