title: 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: BACKGROUND
  Overt 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
  The 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.
  
  
  CONCLUSIONS
  We 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.
  
  
  BACKGROUND
  EUDRACT Number: 2012-001824-36.
authors.forename: Martina
authors.initials: M
authors.lastname: Gaggl
authors.forename: Daniel
authors.initials: D
authors.lastname: Cejka
authors.forename: Max
authors.initials: M
authors.lastname: Plischke
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.forename: Melanie
authors.initials: M
authors.lastname: Fraunschiel
authors.forename: Alice
authors.initials: A
authors.lastname: Schmidt
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Gere
authors.initials: G
authors.lastname: Sunder-Plassmann
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000138:Acidosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000284:Administration, Oral; D001317:Austria; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D018450:Disease Progression; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012107:Research Design; D017693:Sodium Bicarbonate / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D017693:Sodium Bicarbonate