Correction of chronic metabolic acidosis for chronic kidney disease patients: Cochrane systematic review

Abstract

Assessed as up to date: 2013/03/04

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 methods

We searched the Cochrane Renal Group's Specialised Register [up to 4 March 2013] through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

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.

Author(s)

Roderick Paul J, Willis Narelle S, Blakeley Sara, Jones Chris, Tomson Charles

Summary

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

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.

Reviewer's Conclusions

Implications for practice

  • There is no randomised evidence to support the correction of acidosis in pre-ESRD patients by sodium bicarbonate supplementation or in children. Evidence in dialysis patients is very limited.
  • Sodium bicarbonate is an inexpensive and well tolerated drug, and increasing bicarbonate concentration in dialysis fluid is relatively straightforward: both are effective in correcting acidosis. These considerations no doubt help support positive guideline recommendations for acidosis correction.
  • Current guidelines have to rely on extrapolation from the few dialysis trials, non randomised data and consensus. KDOQI recommends maintaining predialysis bicarbonate ≥ 22 mEq/L in all patients (KDOQI 2000), the UK Renal Association has different targets for CAPD (25-29 mmol/L) and HD (20-26 mmol/L) and a non specific target 'within normal range' for pre-ESRD patients (UKRA 2002). The Australian CARI Guidelines for pre-ESRD patients recommend correction to over 22 mol/L based on Grade III evidence (CARI 2005).
  • However it is not known how rigorously identification and correction of acidosis is achieved in pre-ESRD patients. Registry data enable audit in dialysis patients. The potential adverse consequences of volume loading in patients at risk of fluid retention, or of over-correction leading to alkalosis which may precipitate calcium phosphorus and lead to symptomatic hypotension have not been fully addressed. Whether mild acidosis is actually beneficial in dialysis patients as indicated by observational data or whether this is just reverse epidemiology reflecting higher protein intake is uncertain.

Implications for research

RCTs are needed to determine the benefits and risks of correction of acidosis in both pre-ESRD and dialysis patients and could consider at what bicarbonate level to initiate correction and what target level to achieve.

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