Cortisol Dynamics in Outpatients with Chronic Kidney Disease

Presentation Number: SAT-395
Date of Presentation: March 7th, 2015

Alejandro L Arregger*1, Estela Maria Cardoso2, Alfredo Zucchini3, Elvira Aguirre3, Rocio Sanchez3, Alicia Elbert4 and Liliana N Contreras5
1University of Buenos Aires, Buenos Aires CF, Argentina, 2IDIM- CONICET, 3IDIM A Lanari. University of Buenos Aires, 4CERHEA, 5University of Buenos Aires; IDIM-CONICET, Buenos Aires, Argentina


End stage renal disease is associated with functional changes of the HPA axis, however cortisol dynamics have not been fully investigated in earlier clinical stages. We evaluated the circadian variation of salivary cortisol (SAF) and the fast feed-back mechanism in 80 adults aged 18 to 65 y/o, at stages S1 to S4 of chronic renal disease (CKD), 20 in each stage (K/DOQI). None was on steroids, drugs that may affect adrenal function or anticonvulsants. The control group (C) consisted in 40 healthy subjects. Whole saliva samples were obtained at 08 h and 23 h in 2 non-consecutive days for SAF (SAF8 and SAF23, respectively). The fast feed-back was assessed through the overnight 1 mg oral dexamethasone (DEX) suppression test (1mg-DST) in saliva (SAFdex) and serum (total cortisol: Fdex  and free cortisol: FFdex). Serum DEX was simultaneously measured in all samples. Cortisol and cortisol binding globulin (CBG) were assessed by RIA and FF was calculated. DEX was determined by ELISA. Reference values: SAF23 ≤ 3.8 nM; SAF8 ≤ 18 nM; SAFdex ≤ 2.0nM;   Fdex ≤50nM; FFdex ≤ 2.0 nM; circadian variation of SAF is defined as SAF2 3≤ 50% SAF8. Statistics were performed using Mann-Whitney and Spearman tests; the intra-class coefficient of correlation (ICC) was estimated by ANOVA. Results:  Glomerular filtration rate correlated negatively and significantly with SAF 23 (r: -0,343), Fdex: (r: -0,325), SAFdex (r: -0,377) and FFdex (r: -0,436) p<0,004 in all patients. ICC in SAF8 and SAF23 was ≥ 0,83 in  all stages. Five CKD showed impairment of cortisol rhythm. SAF23 was significantly higher in S4 (2,38±1,0nM) and  S3 (2,12±0,8 nM)  than  S2 (1,75±1,1 nM ) and S1 (1,49±0,87nM ), p ≤0.003.  CBG concentrations did not vary either along the different stages of renal disease or between sexes.  SAFdex correlated positively and significantly with FFdex (r: 0,860) and Fdex (r:0,642) p< 0.0001. SAF23   correlated positively with SAFdex (r: 0,499), Fdex (r: 0,422) and FFdex (r: 0,426) p< 0.0001 in all. Two patients in S2, 3 in S3 and 3 in S4 failed to normally suppress. DEX concentrations did not differ between groups (S1: 1.14±0.47, S2: 1.22±057, S3: 1.24±0.47, and S4: 1.31±0.5; p>0.19, ranging from 0.6 to 2.5 ng/ml). DEX concentrations were similar in those who suppressed (DST+): 1.21 ±0.51 ng/ml, those who did not (DST-):  1.41±0.55 ng/ml) and C : 1.32±052 ng/ml; p>0.27. After 2 mg oral DEX all DST- suppressed F (≤50.0 nM ) and SAF (≤ 2.0 nM) reaching serum DEX  concentrations of 2.63±0.84 ng/ml, range 1.8-4.0; significantly higher than with 1 mg (p: 0.0019). These data show that the progressive renal impairment is associated with defects in the circadian variation of cortisol. Derangement of the feed-back mechanism seems not related to plasma DEX bioavailability; inhibition of the HPA axis with higher doses suggests involvement of central sensitivity.


Nothing to Disclose: ALA, EMC, AZ, EA, RS, AE, LNC