The Effect of Correction of Metabolic Acidosis in CKD on Intrarenal RAS Activity

Not Applicable

Completed

• Conditions: Chronic Kidney Disease
• Interventions: Dietary Supplement: Sodium bicarbonate; Dietary Supplement: Sodium chloride

• Registration Number: NCT02896309
• Lead Sponsor: Erasmus Medical Center

Brief Summary

This study evaluates the effect of oral sodium bicarbonate treatment on the intrarenal renin-angiotensin-system in adult patients with a metabolic acidosis and chronic kidney disease. This treatment is compared to sodium chloride treatment, which serves as control for increased sodium-intake and no treatment, which serves as time-control.

Detailed Description

In chronic kidney disease (CKD), as glomerular filtration rate decreases, excretion of hydrogen ions fails, leading to progressive metabolic acidosis (arterial pH \< 7.35 and a serum bicarbonate concentration \< 22 meq/L). Metabolic acidosis enhances further progression of CKD. It is known that the intrarenal renin-angiotensin system (RAS) is stimulated during metabolic acidosis, but it's specific role in the renal response on changes in the acid-base balance is unknown. Correction of metabolic acidosis by administration of bicarbonate is a common intervention in patients with metabolic acidosis due to chronic kidney disease. It is proven to slow down progression of CKD. There is no knowledge on the effect this therapy has on the intrarenal RAS. Since acidosis does not change serum renin levels, and bicarbonate therapy has no effect on blood pressure, it seems to have no effect on the systemic RAS. The investigators hypothesize that bicarbonate therapy diminishes intrarenal RAS activity without affecting the systemic RAS.

Study Timeline

• Study First Submitted: 2016-08-18
• Study Start: 2016-09
• Study First Submitted QC: 2016-09-09
• Study First Posted: 2016-09-12
• Primary Completion: 2018-12-27
• Study Completion: 2018-12-27
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-19
• Last Update Posted: 2019-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• male or female adult (≥18 years)
• chronic kidney disease stage 4, i.e. estimated glomerular filtration rate (MDRD) 15-30 ml/min
• plasma bicarbonate concentration of 15-24 meq/L

Exclusion Criteria

• bicarbonate level >24 meq/L or <15 meq/L, the latter because in that case it seems highly recommended to start sodium bicarbonate suppletion and not to postpone this
• sodium bicarbonate use in the 1 month preceding the study
• heart failure
• liver cirrhosis
• blood pressure >140/90 mmHg despite the use of 3 different antihypertensives
• a kidney transplant in situ
• a history of nonadherence to medication
• use of calcineurin inhibitors (these immunosuppressive drugs are known to induce metabolic acidosis and influence electrolytes and acid-base balance)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium bicarbonate	Sodium bicarbonate	Oral sodium bicarbonate tablets three times daily 1000mg
Sodium chloride	Sodium chloride	Oral sodium chloride capsules two times daily 1000mg

Primary Outcome Measures

Name	Time	Method
Urinary renin concentration	4 weeks

Trial Locations

Locations (1)

Erasmus MC; 🇳🇱 Rotterdam, Zuid Holland, Netherlands