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

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.

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.

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)

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