Despite the advances of medical science over recent decades, hypertension remains a leading cause of death and disability worldwide. Raised systolic blood pressure (SBP) is a major cause and consequence of chronic kidney disease (CKD) and reductions in SBP can delay the progression of CKD. Management strategies to reduce SBP in CKD include pharmacotherapy and dietary sodium/salt restriction. Acidosis (serum bicarbonate <22mmol/l), develops in individuals with CKD and its prevalence increases as CKD advances. Treatment of CKD acidosis can be achieved using sodium bicarbonate/citrate therapy. Concerns exist regarding the potential for the sodium load associated with the use of sodium bicarbonate/citrate to increase blood pressure, despite a lack of evidence directly supporting this. This research aims to systematically review blood pressure response to sodium bicarbonate/citrate therapy in CKD where renal replacement therapy is not used.
Using a population intervention comparison (P.I.O.) framework, a research question was developed which provided the basis for a literature search of academic and grey literature. Databases searched included: MEDLINE (OVID), EMBASE (OVID), CINHAL, AMED, COCHRANE database of systematic reviews (CDSR) and the WHO trials registry. Databases were searched for articles published to September 2017 and re-run in April 2018. Key terms included, but were not limited to: Chronic Kidney Disease, renal insufficiency, acidosis correction, alkali therapy and bicarbonate supplementation. Risk of bias was assessed using the Risk of Bias (RoB) 2.0 or Risk of Bias in Non-Randomised Studies (ROBINS) tools for RCT and NRSi publications respectively. A protocol for this review was written and published on PROSPERO.
A total of 908 studies were identified after duplicates were excluded. Following screening, a total of 6 publications, 4 Randomised Controlled Trial (RCT) and 2 Non-Randomised Studies of interventions (NRSi) were identified, providing 591 participants. All data extracted for SBP and anti-hypertensive /diuretic medication change, was classified as ‘other’ outcome data i.e. not primary or secondary outcome data.
One of the RCT and both NRSi publications were evaluated as high risk of bias. Excess heterogeneity precluded a meta-analysis for blood pressure change following introduction of sodium bicarbonate/citrate. Sub-group and sensitivity analysis demonstrated that in individuals with CKD stage I-V non-renal replacement therapy, the prescription of sodium bicarbonate at a dose of 0.2-0.5mEq/kg is associated with a 0.51 mmHg reduction in SBP (95% CI 0.18-0.84). This result is clinically important since it suggests that sodium bicarbonate does not adversely affect blood pressure. When evaluated using Grading of Recommendations Assessment Development and Evaluation (GRADE) guidance, this outcome was graded as low, which suggests that the true effect is likely to be different from the estimated effect.
A meta-analysis for change in anti-hypertensive and/or diuretic medications as a surrogate for SBP change, was not possible due to a lack of statistical data. A narrative summary of included studies suggests that anti-hypertensive and/or diuretic therapies did not change following the introduction of sodium bicarbonate and exclusion of studies with a high risk of bias or due to high dose of sodium bicarbonate/citrate would not change this result.
Due to the lack of identified studies primarily evaluating the impact of sodium bicarbonate/citrate upon SBP in CKD, this systematic review highlights a gap in research knowledge. Future research is recommended to evaluate the impact of sodium bicarbonate/citrate therapy upon SBP in CKD.
|Date of Award||May 2019|
|Supervisor||Bernice Tighe (Supervisor), Deborah Lycett (Supervisor) & Rizwan Hamer (Supervisor)|