There is limited evidence from three small trials suggesting that the correction of metabolic acidosis trials may have some beneficial effects on both protein and bone metabolism

Roderick PJ, Willis NS, Blakeley S, Jones C, Tomson C

Published Online:

July 8, 2009

In health, protein and amino acids remain in equilibrium however in CKD this balance is disturbed. Metabolic acidosis has been shown to have deleterious effects on protein balance, leading to a negative nitrogen balance, increased protein degradation, increased essential amino acid oxidation, reduced albumin synthesis and a lack of adaption to a low protein diet, and hence is associated with protein energy malnutrition, loss of lean body mass and muscle weakness. Metabolic acidosis is also a factor in the development of renal bone disease, as bone acts as a buffer for excess acid, with loss of mineral resulting from the increase in acid. This review found three small trials in adult haemodialysis patients (n = 117). The evidence for the benefits and risks of correcting metabolic acidosis is very limited with no RCTs in pre-ESRD patients and none in children. These trials suggest there may be some beneficial effects on both protein and bone metabolism but the trials were underpowered to provide strong evidence.

Abstract (click to read)

Background:

Metabolic acidosis is a feature of chronic kidney disease (CKD) due to the reduced capacity of the kidney to synthesise ammonia and excrete hydrogen ions. It has adverse consequences on protein and muscle metabolism, bone turnover and the development of renal osteodystrophy. Metabolic acidosis may be corrected by oral bicarbonate supplementation or in dialysis patients by increasing the bicarbonate concentration in dialysate fluid.

Objectives:

To examine the benefits and harms of treating metabolic acidosis in patients with CKD, both prior to reaching end-stage renal disease (ESRD) or whilst on renal replacement therapy (RRT), with sodium bicarbonate or increasing the bicarbonate concentration of dialysate.

Search strategy:

We searched CENTRAL (The Cochrane Library, issue 4 2005), Cochrane Renal Group's specialised register (November 2006), MEDLINE (1966 - October 2005) and EMBASE (1980 - October 2005).

Selection criteria:

Randomised controlled trials (RCTs), crossover RCTs and quasi-RCTs investigating the correction of chronic metabolic acidosis in adults or children with CKD.

Data collection and analysis:

Outcomes were analysed using risk ratio (RR) and mean difference (MD) for continuous measures.

Main results:

We identified three trials in adult dialysis patients (n = 117). There were insufficient data for most outcomes for meta-analysis. In all three trials acidosis improved in the intervention group though there was variation in achieved bicarbonate level. There was no evidence of effect on blood pressure or sodium levels. Some measures of nutritional status/protein metabolism (e.g. SGA, NP NA) were significantly improved by correction in the one trial that looked in these in detail. There was heterogeneity of the effect on serum albumin in two trials. Serum PTH fell significantly in the two trials that estimated this, with no significant effect on calcium or phosphate though both fell after correction. Complex bone markers were assessed in one study, with some evidence for a reduction in bone turnover in those with initial high bone turnover and an increase in low turnover patients. The studies were underpowered to assess clinical outcomes, in the one study that did there was some evidence for a reduction in hospitalisation after correction.

Authors' conclusions:

The evidence for the benefits and risks of correcting metabolic acidosis is very limited with no RCTs in pre-ESRD patients, none in children, and only three small trials in dialysis patients. These trials suggest there may be some beneficial effects on both protein and bone metabolism but the trials were underpowered to provide robust evidence.

This record should be cited as:

Roderick PJ, Willis NS, Blakeley S, Jones C, Tomson C. Correction of chronic metabolic acidosis for chronic kidney disease patients. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD001890. DOI: 10.1002/14651858.CD001890.pub3

Assessed as up to date:

November 13, 2006

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Primary Review Group:

Renal Group

Health topics:

Kidney disease > Chronic kidney disease > Acidosis control

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

There is limited evidence from three small trials suggesting that the correction of metabolic acidosis trials may have some beneficial effects on both protein and bone metabolism

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