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

Chronic Kidney Disease Clinical Trial

— BIC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02896309
• Other study ID #: NL44415.078.13
• Status: Completed
• Phase: N/A
• Start date: September 2016
• Est. completion date: December 27, 2018

Study information

• Verified date: June 2019
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 27, 2018
• Est. primary completion date: December 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acidosis
• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Sodium bicarbonate

• Sodium chloride

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam	Zuid Holland

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (4)

de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009 Sep;20(9):2075-84. doi: 10.1681/ASN.2008111205. Epub 2009 Jul 16. — View Citation

Henger A, Tutt P, Riesen WF, Hulter HN, Krapf R. Acid-base and endocrine effects of aldosterone and angiotensin II inhibition in metabolic acidosis in human patients. J Lab Clin Med. 2000 Nov;136(5):379-89. — View Citation

Nagami GT. Role of angiotensin II in the enhancement of ammonia production and secretion by the proximal tubule in metabolic acidosis. Am J Physiol Renal Physiol. 2008 Apr;294(4):F874-80. doi: 10.1152/ajprenal.00286.2007. Epub 2008 Feb 20. — View Citation

Ng HY, Chen HC, Tsai YC, Yang YK, Lee CT. Activation of intrarenal renin-angiotensin system during metabolic acidosis. Am J Nephrol. 2011;34(1):55-63. doi: 10.1159/000328742. Epub 2011 Jun 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary renin concentration		4 weeks