Urinary sodium excretion is the main determinant of mineralocorticoid excretion rates in patients with chronic kidney disease

McQuarrie, E.P., Freel, E.M., Mark, P.B. , Fraser, R., Connell, J.M.C. and Jardine, A.G. (2013) Urinary sodium excretion is the main determinant of mineralocorticoid excretion rates in patients with chronic kidney disease. Nephrology Dialysis Transplantation, 28(6), pp. 1526-1532. (doi: 10.1093/ndt/gft007)

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Background: Blockade of the mineralocorticoid receptor (MR) in patients with chronic kidney disease (CKD) improves surrogate cardiovascular outcomes, such as left ventricular mass. Animal models of renal disease support a pathological role of mineralocorticoids, in the context of a high sodium intake. We aimed to assess the regulation of mineralocorticoid biosynthesis in patients with CKD. Methods: Seventy patients with CKD stages 3/4 and 30 patients with essential hypertension (EH) were recruited. Patients underwent detailed clinical phenotyping, drug history and biochemical assessment. Patients completed a 24-h urine collection for measurement of urinary tetrahydroaldosterone (THALDO) and tetrahydrocorticosterone (THDOC) excretion rates (measured using gas chromatography-mass spectrometry) and urinary electrolytes. The factors which correlated significantly with THALDO and THDOC excretion were entered into linear regression models. Results: Patients with EH and CKD were well matched with no significant differences in gender, age or weight. The mean estimated glomerular filtration rate (eGFR) in CKD patients was 38.6/min/1.73 m2. The mean urinary excretion rates of THALDO, THDOC and 24-h urinary sodium (24-h USod) were not significantly different between CKD and EH patients. The level of renal function did not correlate with THALDO or THDOC excretion. In patients with CKD, 24-h USodium (r = 0.614, P < 0.001) and 24-h UPotassium (r = 0.538, P < 0.001) were positively correlated with THALDO excretion. On multivariate linear regression analysis, 24-h USod was the strongest independent predictor (P = 0.004) of THALDO and THDOC excretion in CKD. In patients with EH, no relationship was seen between mineralocorticoid excretion and 24-h urinary sodium excretion. Conclusions: In patients with CKD, 24-h urinary sodium excretion is the strongest positive predictor of urinary mineralocorticoid excretion. The nature of this relationship is unexpected, novel, not seen in patients with EH and may explain the association seen between high urinary sodium excretion, mineralocorticoids and poor outcomes in patients with CKD.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McQuarrie, Dr Emily and Connell, Professor John and Freel, Dr Marie and Fraser, Prof Robert and Mark, Professor Patrick and Jardine, Professor Alan
Authors: McQuarrie, E.P., Freel, E.M., Mark, P.B., Fraser, R., Connell, J.M.C., and Jardine, A.G.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Nephrology Dialysis Transplantation
Publisher:Oxford University Press
ISSN (Online):1460-2385
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
496251Translational studies on the role of corticosteroids in cardiovascular diseaseMarie FreelMedical Research Council (MRC)G0802803RI CARDIOVASCULAR & MEDICAL SCIENCES