CKD: Dietary Protein (2001)


Fouque D, Wang P, Laville M, Boissel J-P.  Low protein diets delay end-stage renal disease in non-diabetic adults with chronic renal failure.  Nephrol Dial Transplant 2000; 15:1986-1992.

Worksheet created prior to Spring 2004 using earlier ADA research analysis template.
PubMed ID: 11096144
Study Design:
Meta-analysis or Systematic Review
M - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

The purpose of this meta-analysis was to determine the efficacy of low protein diets in preventing the natural progression of chronic renal failure towards end-stage renal disease and therefore, delaying the need for starting maintenance dialysis.

Inclusion Criteria:

1. Randomized controlled trials - random assignment to usual protein diet (0.8 g/kg) or moderate protein restriction (0.6 g/kg) or severe protein restriction (0.3 g/kg) regardless of supplementation with amino acids or ketoacids.

2. Cross-over studies in which starting intervention was randomly allocated.

3. Study period of >12 months.

4. Subjects with a diagnosis of moderate to severe CRF as estimated either by serum creatinine, creatinine clearance or GFR.

Exclusion Criteria:

1. Studies including those with diabetes.

2. Studies including children

Description of Study Protocol:


Study search was done using:

Medine and Embase between Jan 1966 and June 1999

Hand search of Congress abstracts (Am Soc of Nephrology since 1990, European Dialysis Transplant Assoc since 1985 and International Society of Nephrology since 1987).

Contacting authors of published work.


Meta-analysis of randomized controlled trial of usual protein diet (0.8 g/kg) or moderate protein restriction (0.6 g/kg) or severe protein restriction (0.3 g/kg). Cross-over studies in which starting intervention was randomly allocated were also included.

Blinding used (if applicable)

No blinded follow-up of treatment

Intervention (if applicable)

Standard protein intake (0.8g/kg/day) or greater versus a moderate (0.6g/kg/day) to severe protein restriction (0.3g/kg/day) regardless of supplementation with essential amino acids or ketoacids.

Statistical Analysis

The number of patients originally allocated to each treatment group was noted and an “intention to treat” analysis was used.

Odds ratio, percentage difference, Peto, Mantel-Haensze were conducted.

Data was adjusted for a 1-yr period in order to compare treatment efficiency in trials of different durations.

Data Collection Summary:

Timing of Measurements

Trials were conducted from 1975 to 1999. Medline and Embase were searched from January 1966 through June 1999. Congress abstracts; American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, and International Society of Nephrology since 1987.

Dependent Variables

  • Rate of GFR decline measured by plasma clearance of Cr-EDTA
  • Rate of GFR decline measured by plasma clearance of iothalamate
  • Serum creatinine
  • Renal death including death from any cause
  • Starting hemo- or peritoneal dialysis
  • Receiving a kidney transplant

Independent Variables

  • Standard protein intake (0.8g/kg/day) or greater versus a moderate (0.6g/kg/day) to severe protein restriction (0.3g/kg/day) regardless of supplementation with essential amino acids or ketoacids.


Description of Actual Data Sample:

Initial N: 1,494 patients, 753 in the restricted protein groups and 741 in the unrestricted or higher protein intake groups.

Attrition (final N): See above

Age: Mean age of patients in the studies ranged from 44 to 62 years.

Ethnicity: Not mentioned

Other relevant demographics: Gender (Male/Female) was as follows: .54, .37, .54, .58, .67, .63, and .60 reflecting the higher male prevalence of renal disease.


Location:  Worldwide studies

Summary of Results:

Other Findings:

The protein intakes for the 7 studies ranged from 0.4 to 0.8 g/kg/d with a mean intake of ~0.6 gm/kg/d.

The level of renal insufficiency was moderate or severe. There was no heterogeneity between studies (P=0.59). There was some heterogeneity between diets.

Based on urinary urea excretion, the actual reduction in dietary protein intake between groups in each study was less than expected and close to 0.2 g/kg/d, 0.25 g/kg/d, 0.3 g/kg/d and 0.35 g/kg/d.

 242 renal deaths were recorded, 101 in the low protein diet group and 141 in the higher protein diet group, giving an odds ratio of 0.61 with a 95% CI of 0.46 to 0.83 (P=0.006).

There was a 39% relative risk reduction in renal death in favor of a restricted protein intake.

Reduction in the Odds of Renal Death in Seven Prospective Randomized Studies of Protein Restriction


Experimental (n/N)

Control (n/N)

Odds Ratio (95% CI fixed)

Jungers 1987



.29 [.04,2.11]

Malvy 1999



.37 [.12,1.17]

Williams 1991



1.09 [.39,3.02]

Ihle 1989



.26 [.07,.89]

Rosman 1989



.73 [.41,1.30]

Locatelli 1991



.61 [.34,1.09]

Klahr 1994



.65 [.35,1.21]

Total (95% CI)



.61 [.46,.83]

Author Conclusion:

The fact that the actual patient protein intake was greater than prescribed in all studies suggests that regular dietitian services be proposed. Moreover, it has been demonstrated that patients with CRF without intervention by the dietitian will express a progressive decline in protein and energy intakes, potentially contributing to the decline in nutritional markers.

In contrast, feasibility of low protein diets has been shown in large studies with convincing results, highlighting the fact that interested teams can motivate patients to the point of excellent compliance and optimal nutritional benefit, a goal that should be reached for most patients in all renal units. Factors other than diet therapy have demonstrated a renal protective effect and to delay end-stage renal disease. These include angiotensin-converting enzyme inhibitors, blood pressure control, and optimal glucose monitoring in diabetic patients.

It cannot be derived from this meta-analysis that low protein diets reduce the progression of kidney disease since the decision to begin dialysis is often based on BUN and lower intakes of dietary protein would lower serum BUN, postponing dialysis.

Funding Source:
University/Hospital: Hopital Edouard Herriot, University of California
Reviewer Comments:

A limitation of some of the studies included in this meta-analysis was the use of serum creatinine rather than GFR as a marker for renal disease. Based on these studies, even a small reduction in dietary protein intake will postpone renal replacement therapy—dialysis or transplant.

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