Hpa axis disregulation due to impaired glucocorticoid negative feedback in patients with chronic kidney disease
L. Boswella (Dr), M. Blascoa (Dr), LF. Quintanaa (Dr), A. Vega-Beyhartb (Dr), J. Viaplanac (Ms), G. Rodrigueza (Ms), D. Diazd (Ms), C. Vilardelle (Dr), M. Moraa (Dr), I. Halperina (Dr), AJ. Amora (Dr), G. Casalsa (Dr), FA. Hanzu*a (Dr)
a Hospital Clínic de Barcelona, Barcelona, SPAIN ; b Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS),, Barcelona, SPAIN ; c Fundació Clínic for Biomedical Research, Barcelona, SPAIN ; d IDIBAPS, Barcelona, SPAIN ; e Endocrinology and Nutrition Department, Althaia University Health Network, Manresa, Spain, Manresa, SPAIN
Aims: A few studies have shown disturbances in the hypothalamic-pituitary-adrenal (HPA) axis in chronic-kidney-disease (CKD), of unknown extent and clinical implications. We aimed to study the HPA axis in patients with CKD and its association with kidney impairment and metabolic disturbances.
Methods: Cross-sectional controlled study. 48 patients with CKD stages I-II (eGFR through CKD-EPI equation >60), stage III and stage IV CKD with preserved diuresis were included and paired with 24 healthy controls by age, sex and BM. Exclusion criteria were: active glucocorticoid, immunosuppressive or anti-inflammatory treatment, diabetes mellitus, morbid obesity, drugs interfering with the HPA axis or pseudo-Cushing states. Subjects underwent clinical and analytical assessment of metabolic comorbidities, body composition analysis using DEXA and a thorough evaluation of the HPA axis.
Results: We included 72 subjects (age 53±12years, 52% women, BMI 26±4kg/m2). A stepped increase in hypertension and dyslipidaemia prevalence as well as increasing levels of glucose, triglycerides and 24h-urinary protein excretion were observed with worsening kidney function (p<0.05 for all). Both plasmatic insulin levels and visceral adipose tissue volume measured using DEXA increased with worsening kidney function (p<0.001).
A higher ACTH (23 vs. 17pg/mL, p=0.048) and less cortisol supression after 1mg dexamethasone-suppression-test (DST) (1.2 vs. 0.9µg/dL, p<0.001) were seen in patients with CKD compared to controls. No differences in ACTH were observed according to CKD stage. 24h-urinary-free-cortisol was decreased in stages III-IV compared to CKD stages I-II and controls (p<0.001). Of all, 24% patients with CKD had a post-DST cortisol >2mcg/dL (2 [14%] in CKD stage III and 9 [60%] in the stage-IV-group); 45% persisted with cortisol >2mcg/dL after a low-dose 2-day-DST (2mg/6h), all with stage IV (p<0.001). No differences were observed in basal cortisol or cortisol-binding-globulin.
In the whole cohort, cortisol after DST was lineally inversely correlated with eGFR (β -19.8, p<0.001). Cortisol after DST (OR 11.9, 95%CI 1.5-97, p=0.021) and glucose (OR 1.3, 95%CI 1.1-1.5, p=0.003) were independently associated with an eGFR <30ml/min/m2.
Conclusions: Negative feedback of the HPA axis is impaired in patients with CKD and correlates with disease stage. This should be taken into account when hypercortisolism is suspected and explored in this context.
The author has declared no conflict of interest.