DM: Protein (2007)


Meloni C, Morosetti M, Suraci C, Pennafina MG, Tozzo C, Taccone-Gallucci M, Casciani CU.  Severe dietary protein restriction in overt diabetic nephropathy: Benefits or risks?  J Renal Nutr 2002;12:96-101.

PubMed ID: 11953922
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To evaluate the influence of dietary protein intake on progression of chronic renal failure in patients with overt diabetic nephropathy as well as their risk of malnutrition.
Inclusion Criteria:
  • Type I or II diabetes controlled by insulin
  • Nephropathy (not defined specifically)
  • Hypertension controlled for at least 3 months with ACE inhibitors and Ca channel blockers


Exclusion Criteria:
  • Clinical or biochemical signs of malnutrition
Description of Study Protocol:

Recruitment - Nephrology clinic outpatients meeting criteria

Design - Randomized Controlled Trial.

Blinding used:  not possible - lab tests.

Intervention - low protein diet (0.6g/kg/d) or usual protein intake for 12 months

Statistical Analysis - Student t test and ANOVA were used as statistical analysis. 

Data Collection Summary:

Timing of Measurements - monitored monthly, but data only given for baseline and 12 months

Dependent Variables

  • Glomerular filtration rate by 51Cr EDTA
  • Serum albumin and prealbumin
  • Body weight and obesity index
  • Blood pressure

  • Glycemia

  • Hemoglobin A1C 

Independent Variables

  • Dietary protein - monitored by diet questionnaire and 24 h urinary N; only questionnaire data given
  • Dietitian staff also controlled dietary adherence at the patient's home during the study period

Control Variables:


Description of Actual Data Sample:

 Initial N: 69 subjects, 38 M, 31 F

Attrition (final N): 69 subjects.  34 in free-protein diet, 35 in low-protein diet.

Age: 54.4 + 15.3 y

Ethnicity: white

Other relevant demographics:

Anthropometrics: groups matched for similar mean GFR value and nutritional status using standard laboratory values at baseline

Location: Nephrology and Dialysis, S Eugenio Hospital, Rome, Italy


Summary of Results:



Low Protein Treatment Group

12 mon

Usual Protein Control group

12 mon

Statistical Significance of Group Difference

Dietary protein 0.68 + 0.40 1.38 + 0.30 <0.01
Energy intake 1823 +/- 239 2217 +/- 304 <0.05
GFR decline 6.15 +/- 1.61 6.26 +/- 1.84 NS
Serum phosphate 4.0 + 0.7 5.1 + 0.7 <0.05
Serum prealbumin 23.5 + 9.7 40.9 + 3.2 <0.05

Serum albumin

 3.7 + 0.4

 4.3 + 0.3


Proteinuria g/24h

 1.3 + 0.5

 2.4 + 1.0


Other Findings

The protein intake was significantly different in the 2 groups of patients, whereas the average decline of GFR during follow-up was comparable.  Decline in GFR was similar between patients with type 1 and type 2 diabetes.

In the low-protein diet group, serum prealbumin concentration significantly decreased after 9 months, whereas serum albumin decreased at the end of the study.

The mean body weight and obesity index decreased significantly in the low-protein group after 12 months (both P < 0.01) whereas it remained stable in the free protein group.

Author Conclusion:
Our data show that severe dietary protein restriction does not seem to delay the progression of renal disease in patients with over diabetic nephropathy.  Severe restrictions of dietary protein intake for long periods of time are not indicated in diabetic patients with overt diabetic nephropathy.  In fact, the progression of renal failure is not slowed down, and the risk of malnutrition is present.
Funding Source:
University/Hospital: S. Eugenio Hospital Rome Italy, Tor Vergata
Reviewer Comments:
The conclusions are severely compromised by the loss of weight in the low-protein group, which may have offset the benefits, such as decrease in proteinuria.  The authors also point out that dietary protein restriction may only be beneficial in earlier stages of diabetic nephropathy than found in the patients studied.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes