Effect of oral sodium bicarbonate supplementation on progression of chronic kidney disease in patients with chronic metabolic acidosis: study protocol for a randomized controlled trial (SoBic-Study)

Abstract

BackgroundOvert chronic metabolic acidosis in patients with chronic kidney disease develops after a drop of glomerular filtration rate to less than approximately 25 mL/min/1.73 m2. The pathogenic mechanism seems to be a lack of tubular bicarbonate production, which in healthy individuals neutralizes the acid net production. As shown in several animal and human studies the acidotic milieu alters bone and vitamin D metabolism, induces muscle wasting, and impairs albumin synthesis, aside from a direct alteration of renal tissue by increasing angiotensin II, aldosteron and endothelin kidney levels. Subsequent studies testing various therapeutic approaches in very selected study populations showed that oral supplementation of the lacking bicarbonate halts progression of decline of renal function. However, due to methodological limitations of these studies further investigations are of urgent need to ensure the validity of this therapeutic concept.Methods/DesignThe SoBic-study is a single-center, randomized, controlled, open-label clinical phase IV study performed at the nephrological outpatient service of the Medical University of Vienna. Two-hundred patients classified to CKD stage 3 or 4 with two separate measurements of HCO3- of <21 mmol/L will be 1:1 randomized to either receive a high dose of oral sodium bicarbonate with a serum target HCO3- level of 24 ± 1 mmol/L or receive a rescue therapy of sodium bicarbonate with a serum target level of 20 ± 1 mmol/L. The follow up will be for two years. The primary outcome is the effect of sodium bicarbonate supplementation on renal function measured by means of estimated glomerular filtration rates (4-variable-MDRD-equation) after two years. Secondary outcomes are change in markers of bone metabolism between groups, death rates between groups, and the number of subjects proceeding to renal replacement therapy across groups. Adverse events, such as worsening of arterial hypertension due to the additional sodium consumption, will be accurately monitored.DiscussionWe hypothesize that sufficiently balanced acid–base homeostasis leads to a reduction of decline of renal function in patients with chronic kidney disease. The concept of an exogenous bicarbonate supplementation to substitute the lacking endogenous bicarbonate has existed for a long time, but has never been investigated sufficiently to state clear treatment guidelines.Trial registrationEUDRACT Number: 2012-001824-36

Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study

“…Several interventional studies have investigated and are investigating the potential benefits of normalizing low bicarbonate with alkaline therapy in patients with CKD (28,(38)(39)(40). This has not been evaluated in persons without CKD.…”

Oral Sodium Bicarbonate Supplementation Does Not Affect Serum Calcification Propensity in Patients with Chronic Kidney Disease and Chronic Metabolic Acidosis

“…Exclusion criteria were malignant disease or within 5 years of successful treatment of such, morbid obesity (body mass index >40 kg/m 2 ), chronic inflammation (C reactive protein >10 mg/dL, reference: <0.5 g/dL), current immunosuppressive medication, poorly controlled blood pressure (>150/90 mm Hg despite the use of four agents), overt congestive heart failure, or known peanut or soy allergy (both ingredients of study medication). Dependent on randomization, patients were treated with Nephrotrans® 840 mg tablets (sodium bicarbonate; MEDICE Pharma Pütter GmbH & Co. KG, Iserlohn, Germany) according to a treatment algorithm [25]. For patients receiving sodium bicarbonate supplementation the dose was constant for the 4 weeks of follow-up in this study.…”

“…We obtained demographic and medical information as well as a laboratory analysis at randomization as detailed elsewhere (visit 1 and 2 of the SoBic-study) [25]. After 4 weeks all patients underwent visit 3 (week 4) for a subsequent laboratory investigation, assessment of vital signs, body weight, and adverse events (Fig.…”

“…The SoBic-study (EUDRACT: 2012-001824-36, 7/12/2012) [25] is an ongoing randomized-controlled trial in CKD-G3 and G4 patients with chronic metabolic acidosis (serum HCO 3 – ≤21 mmol/L) at the Renal Outpatient Clinic at the Medical University of Vienna. The aim of the parent study is to evaluate the effect of normalizing serum bicarbonate (HCO 3 – ) levels to 24 ± 1 mmol/L (intervention group) compared to serum bicarbonate (HCO 3 – ) levels of 20 ± 1 mmol/L (rescue group) on renal function (MDRD-eGFR) over 2 years.…”

Electrolyte and Acid-Base Disorders in Chronic Kidney Disease and End-Stage Kidney Failure

“…An appropriate upper target is important as studies have shown a U-shaped association between mortality and serum bicarbonate, with elevated serum bicarbonate (>26 mmol/l) being associated with increased mortality risk [51,59]. There are several ongoing randomized clinical trials evaluating the effect of NaHCO 3 on renal function, rate of CKD, mortality, bone turnover markers, muscle strength and quality of life [60,61,62]. The results from these trials will clarify the effects of oral bicarbonate as well as an appropriate upper serum bicarbonate target.…”