CKD: Dietary Protein (2001)

Citation:

Kasiske BL, Lakatua JD, Ma JZ, Louis TA.  A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function. Am J Kidney Dis. 1998; 31:954-961.

Worksheet created prior to Spring 2004 using earlier ADA research analysis template.
PubMed ID: 9631839
 
Study Design:
Meta-analysis or Systematic Review
Class:
M - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
The purpose of this study was to examine the effects of different levels of dietary protein restriction on the rate of decline in GFR in both randomized and nonrandomized controlled trials.
Inclusion Criteria:

Studies published between 1980 through the end of 1996. Medline and bibliographies found in published reviews were used to locate studies.

1. Studies evaluating the effect of protein intake on the rate of decline in renal function over at least 6 months.

2. Controlled studies with either RCT, prospective study (not RCT), or evaluation period preceding the study period.

3. Data on rate of decline in renal function reported for both control and study groups.

4. Random effects and fixed effects models were used for data analysis.

Exclusion Criteria:

1. Trials that reported retrospective data on treatment.

2. Clinical trials of children because the amounts of dietary protein in both treatment and control groups were substantially higher than those used to study adults.

3. Trials that appeared to report data on the same patient.

Description of Study Protocol:

Recruitment

Studies published from 1980 through the end of 1996 using Medline and bibliographies found in published reviews.

Design

Meta-analysis.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Studies were reviewed independently by two of the authors. Study quality indicators were examined: (1) publication as a peer-reviewed report, (2) random allocation to treatment and control group (3) use of parallel control group design, (4) assessment of dietary protein intake measuring urea nitrogen accrual, and (5) analysis of results by intention to treat.

24 controlled (randomized and nonrandomized) trials:

13 RCT: unweighted mean dietary protein content was .68 +/- .11 g/kg/d in treatment groups (.66 +/- .10 g/kg/d in nine studies that included mostly nondiabetic patients and .73 +/- .15 g/kg/d in the four studies that included mostly diabetic patients) and 1.01 +/- .32 g/kg/d in the control groups.

11 nonrandomized trials: mean dietary protein content was .61 +/- .14 g/kg/d in the treatment groups and 1.02 +/- .28 g/kg/d in the control groups.

Statistical Analysis

Weighted regression analysis was used to determine the reasons for the differences in the results of the 13 randomized trials along with the 11 other nonrandomized controlled trials.

 

Data Collection Summary:

Timing of Measurements

Studies published from 1980 through the end of 1996 using Medline and bibliographies found in published reviews.

Dependent Variables

  • The rate of decline in renal function using the slope of serial GFR
  • Creatinine clearance
  • Urea nitrogen.

Independent Variables

  • Randomized Trial:  Dietary protein intake .68 +/- .11 g/kg/d in treatment groups (.66 +/- .10 g/kg/d in nine studies that included mostly nondiabetic patients and .73 +/- .15 g/kg/d in the four studies that included mostly diabetic patients) and 1.01 +/- .32 g/kg/d in the control groups.
  • Nonrandomized Trial:  Dietary protein intake .61 +/- .14 g/kg/d in the treatment groups and 1.02 +/- .28 g/kg/d in the control groups.

Control Variables

Description of Actual Data Sample:

Initial N: 13 randomized controlled trials included 1,919 patients (range, 14 to 840 patients/study).  The other 11 nonrandomized controlled trials included 2,248 patients (range 12 to 840 patients/study).

Attrition (final N): See above.

Age: Not mentioned

Ethnicity: Not mentioned

Other relevant demographics: Not mentioned

Anthropometrics:

Location:  Worldwide studies

Summary of Results:

The pooled results demonstrated that protein restriction reduced the rate of decline in renal function by 0.53 mL/min/yr (95% CI, 0.08 to 0.98 mL/min/yr).

It appeared that the magnitude and variability of the treatment effects were inversely proportional to the size of the studies. In a funnel plot of treatment effects vs. study sample size, the smaller studies tended to more often report positive results, indicating possible publication bias in favor of low-protein diets.

With removal of 1 large study with a small difference in protein intake between treatment and control groups, the results of the remaining 12 studies were: Protein restriction reduced the rate of decline in renal function by 0.66 mL/min/yr (95% CI, 0.18 to 1.14 mL/min/yr). The mean protein intake was 0.61+0.14 g/kg/d in the treatment group and 1.02+0.28 g/kg/d in the control group, a difference of 0.41+0.26 g/kg/d.

The effect of dietary protein restriction (GFR decline in treatment – control) was substantially less in RCT vs. nonrandomized (regression coefficient, -5.2 mL/min/yr; (95% CI, -7.8 to –2.5 mL/min/yr; P<0.05) and relatively greater in those with diabetes vs. nondiabetics: 5.4 mL/min/yr; 95% CI, 0.3to 10.5 mL/min/yr; P<0.05), while there was a trend toward greater effects with each additional year of follow-up and the duration of follow-up was short in most trials.

 

Effect of a Low-Protein Diet on the Rate of Change in GFR (Low-Protein Control Diet, mL/min/yr)

Variable

Fixed-Effects Model

Random-Effects Model

Random design

-5.15 (-7.77 to –2.53)

-5.23 (-8.47 to –2.00)

Diabetes

5.40 (0.31 to 10.50)

6.25 (2.07 to 10.44)

Follow-up (yr)

2.08 (-0.05 to 4.20)

1.49 (-0.32 to 3.29)

Constant

1.40 (-1.37 to 4.17)

2.95 (-0.73 to 6.62)

Multiple linear regression coefficients and 95% CIs for independent effects of variables on the difference in the rate of GFR decline between low-protein and control diets. A positive coefficient indicates that the variable favored a low-protein compared with a control diet.

Author Conclusion:

The results of this meta-analysis suggest that reduced dietary protein intake retards the rate of decline in GFR among patients with renal disease. However, the magnitude of the effect of dietary protein restriction was relatively small.

The present analysis indicated that the effects of a low-protein diet may be greater in patients with diabetes. However the number of diabetic patients studied was small.

Analysis suggests that better therapies are needed to retard the rate of GFR decline in patients with renal disease.

Funding Source:
University/Hospital: Hennepin Medical Center, University of Minnesota
Reviewer Comments:

The small benefit of protein restriction in early renal disease makes it difficult to routinely recommend a protein restriction when these patients often have anorexia and protein calorie malnutrition.

Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
 
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes