Meta-analysis or Systematic Review

M - Click here for explanation of classification scheme.

POSITIVE: See Quality Criteria Checklist below.

To assess the effects of dietary protein restriction on the progression of diabetic nephropathy in patients with diabetes.

• Trials with interventions that lasted a minimum of four months
• Four months was selected because it allows serum creatinine levels to reach a steady state (according to Zeller 1991)
• Trials involving people of any age with either type 1 or type 2 diabetes and nephropathy
• Studies published in any language were included.

• Any designs that were flawed or included a flawed analysis
• Insufficient details of diet given or if the intervention was immediately pre-dialysis
• If results for individuals with diabetes were not given separately.

Recruitment

• The Cochrane Library (issue 3, 2006), Medline (until May 2006), EMBASE (until May 2006), ISI Proceedings (until July 2006) and the Science Citation Index Expanded (until July 2006) were all searched to identify trials
• All records from each database were imported to the bibliographic package, Reference Manager version 10, and checked for duplicates and merged into one core database
• After reviewing titles and abstracts, full articles were retrieved for further assessments if the information given suggested the study might be relevant
• Study selection was independently performed by two reviewers.

Design

Systematic review.

Intervention

A modified or restricted protein diet for at least four months.

Statistical Analysis

• Data concerning details of the study population, intervention and outcomes were extracted independently by two reviewers using a standard data extraction sheet. Data on participants, interventions and outcomes were abstracted.
• Assessment of the methodological quality of reporting of RCTs was based largely on the quality criteria specified by Schulz and Jadad
• In the event of substantial clinical or methodological or statistical heterogeneity, study results were not planned to be combined in a meta-analysis
• Funnel plots were planned to be used in exploratory data analyses to assess for the potential existence of small study bias
• Data on changes in glomerular filtration rate (GFR) were summarized in a meta-analysis for trials with people with type 1 diabetes (only RCTs)
• Sub-group analyses were planned to be only performed if one of the primary outcome parameters demonstrated statistically significant differences between treatment groups. Sub-group analyses such as gender, age and type 1 vs. type 2 diabetic people were performed.
• Sensitivity analysis was performed in order to explore the influence on effect size
• The robustness of the results was also tested by repeating the analysis using different measures of effect size (risk difference, odds ratio, etc.) and different statistical models (fixed and random effects models).

 Dependent Variables

• Primary outcomes included all-cause mortality, end-stage renal disease, and glomerular filtration rate (GFR)
• Secondary outcomes included adverse effects including nutritional status, measures of compliance with low-protein diet (LPD), health related quality of life and costs.

Independent Variables

• A modified or restricted protein diet for at least four months
• In all studies, the comparison intervention was usual (free or uncontrolled) protein diet (actual protein intake 1g to 2g per kg per day)
• In all studies, the intervention was a LPD containing from 0.3g to 0.8g per kg per day
• In two studies the intervention diet was a low-protein vegetarian diet.

• Initial N: A total of 12 studies (nine RCTs, three before and after) including from eight to 160 people with type 1 and type 2 diabetes
• Attrition (final N): A total of 12 studies (nine RCTs, three before and after) including from eight to 160 people with type 1 and type 2 diabetes
• Location: Worldwide studies.

 

Key Findings

• Only one study explored all-cause mortality and end-stage renal disease (ESRD) as endpoints
• The relative risk (RR) of ESRD or death was 0.23 (95% CI: 0.07 to 0.72) for patients assigned to a low protein diet (LPD)
• Pooling of the seven RCTs in patients with type 1 diabetes resulted in a non-significant reduction in the decline of glomerular filtration rate (GFR) of 0.1ml per minute per month (95% CI: -0.1 to 0.3) in the LPD group
• For type 2 diabetes, one trial showed a small insignificant improvement in the rate of decline of GFR in the protein-restricted group and a second found a similar decline in both the intervention and control groups
• Actual protein intake in the intervention groups ranged from 0.7g to 1.1g per kg per day
• One study noted malnutrition in the LPD group
• No data was found on the effects of LPDs on health related quality of life and costs.

• Based on 12 studies, the results show that reducing protein intake for at least an average four-month period appears to slightly slow progression of diabetic kidney disease to renal failure but not statistically significantly so.
• Questions concerning the level of protein intake and compliance remain, as a low-protein diet can be difficult to adhere to, especially over the long term. Further long-term research on large representative groups of patients with type 1 and type 2 diabetes mellitus is necessary.
• Because of variability amongst patients, there might perhaps be a six-month therapeutic trial of protein restriction in all individuals, with continuation only in those who responded best.
• Trials are required of different types of protein; reducing the amount of animal protein is the usual method but some evidence suggests that a shift from red meat to white meat and fish or vegetables may give similar results.
• We found no data on the effects of low-protein diet on health-related quality of life and costs.

Other:

Funding not declared

The authors noted that the present body of evidence is limited and studies that are long term and that report outcomes such as end-stage renal disease (ESRD) are needed. These studies also need to examine the balance between efficacy, adverse effects and compliance.