Efficacy and safety of a low-sodium diet and spironolactone in patients with stage 1-3a chronic kidney disease: a pilot study

Abstract

Background: Excessive salt intake is associated with the deterioration of chronic kidney disease (CKD). Aldosterone is also known as an independent risk factor for kidney injury. Dietary sodium intake acts as a main stimulator in aldosterone-mediated kidney injury. Hence, this study aimed to further investigate the renal protective effects and safety of a low-sodium diet in combination with spironolactone (SPL) in stage 1-3a CKD.

Methods: This single-center, SPL-blinded randomized controlled trial recruited patients with stage 1-3a CKD, randomized into three groups, low-sodium (3 g/d salt) + placebo, medium-sodium (5 g/d salt) + SPL, and low-sodium (3 g/d salt) + SPL. Patients received 12 weeks of intervention. The primary and secondary endpoints were 24-h urine protein and estimated glomerular filtration rate (eGFR) at the end of the intervention, respectively.

Results: A total of 74 patients were analyzed eventually. Significantly decreased 24-h urine protein was found in all three groups, from 0.37 to 0.23 g/d (P = 0.004) in the low-sodium+placebo group, from 0.44 to 0.29 g/d (P = 0.020) in the medium-sodium+SPL group, and from 0.35 to 0.31 g/d (P = 0.013) in the low-sodium +SPL group. There were no significant differences among the three groups in 24-h urine protein amount change after intervention from pre-treatment values (P = 0.760, ITT set). The results of the 24-h urine protein by using PP set analysis was similar to the ITT set. No significant differences in eGFR, nutritional, metabolic, inflammatory, and other biomarkers were observed across all three groups (P > 0.05). No safety signal was observed.

Conclusion: No additional benefit was observed when SPL was prescribed to patients already on a low-sodium diet (3.0 g/d). Still, small doses of SPL may benefit patients with poor sodium restriction. A combination of short-term low-dose SPL and ARB is safe for patients with stage 1-3a CKD, but blood potassium must be regularly monitored.

Trial registration: Name of the registry: Chinese clinical trial registry.

Trial registration number: ChiCTR1900026991. Date of registration: Retrospectively registered 28 October 2019. URL of trial registry record: http://www.chictr.org.cn/searchproj.aspx?title=&officialname=&subjectid=&secondaryid=&applier=&studyleader=ðicalcommitteesanction=&spo.

Keywords: Chronic kidney disease; Low-sodium diet; Mineralocorticoid receptor antagonist; Safety; Spironolactone.