Clinical trial NCT02896309: The Effect of Correction of Metabolic Acidosis in CKD on Intrarenal RAS Activity
Official title: The Effect of Correction of Metabolic Acidosis in CKD on Intrarenal RAS Activity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2016-09-12
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Urinary renin concentration
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid Holland
Study officials:
affiliation: Erasmus Medical Center
name: Ewout J Hoorn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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. doi: 10.1067/mlc.2000.110371.