Aim: In chronic kidney disease (CKD) elevated aldosterone (Aldo) levels are a poor prognostic indicator, particularly in the context of a high dietary sodium intake, through unclear mechanisms. Blockade of the mineralocorticoid receptor (MR) improves surrogate patient outcomes. We hypothesised that regulation of aldosterone biosynthesis is disordered in CKD and aimed to compare this in a cohort of patients with CKD with subjects with essential hypertension (EH).
Methods: Seventy patients with CKD stages 3/4 and 30 patients with EH were recruited. Patients underwent 24 h urine collection for urinary tetrahydroaldosterone (THAldo) and tetrahydrodeoxycorticosterone (THDOC) (measured using GCMS) and urinary electrolytes. Factors which correlated significantly with THAldo were entered into a linear regression model.
Results: Mean age was 57.4 years, 78% of patients were male, mean SBP was 149 mmHg, mean DBP 86 mmHg, mean BMI was 29.3 kg/m2. Patients with EH and CKD demonstrated no significant differences in gender, age or weight. Drug therapies were similar across the cohorts although EH patients were significantly more likely to be prescribed thiazide diuretics (56% vs. 6%). Urinary excretion of THAldo (58.4 μg/24 h) and sodium (160.7 mmol/24 h) did not differ between patient groups. Mean eGFR in CKD patients was 40.3 ml/min per 1.73 m2.
In EH patients, the strongest correlate with THAldo excretion was THDOC. In CKD, THAldo (0.917, P<0.001) correlated positively and significantly with THDOC excretion, as did 24 h USodium (r=0.614, P<0.001) and 24 h UPotassium (0.538, P<0.001). These relationships were not seen in EH. On multivariate linear regression analysis 24 h USodium was the strongest independent predictor (P=0.004) of THAldo excretion in CKD.
Conclusions: In patients with CKD, 24 h urinary sodium is the strongest predictor of THAldo excretion. This relationship is unexpected, novel, not seen in patients with EH and may help explain the association between high urinary sodium excretion, aldosterone and poor outcomes in patients with CKD.