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CKD: Sodium Requirements (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To investigate the blood pressure (BP) effect of sodium intake and weight changes in a subset of  the modification of diet in renal disease (MDRD) in study patients who were hypertensive at the start of the trial.

Inclusion Criteria:
  • Subset of patients who were hypertensive in the beginning of the MDRD study
  • Mean arterial pressure (MAP) of less than 107mm Hg for patients 60 years of age or younger and less than 113mm Hg for patients older than 60 years old
  • MAP with goals of less than 92mm Hg for younger patients and less than 98mm Hg for older patients.
Exclusion Criteria:

Not specified.

Description of Study Protocol:

Recruitment

States these have been previously published and lists references.

Design

States these have been previously published & lists references.

  • Eligible MDRD study subjects were first stratified by baseline renal function and then randomized to a usual or low mean arterial blood pressure (MAP) goal:
    • Study Group A: GFR 25 to 55ml per minute per 1.73m2 
    • Study Group B: GFR 13 to 24ml per minute per 1.73 m2
  • Patients in Group A were randomized to receive 1.3g protein and 16 to 20g phosphorus per kg of standard body weight (SBW) or 0.575g protein and 5 to 10g phosphorus per kg SBW
  • Patients in Group B were randomized to receive 0.575g per kg protein with 5 to 10mg per kg of phosphorus or 0.28g per kg of protein and 4 to 9mg per kg of phosphorus per kg.

MAP (two-thirds diastolic and one-third systolic) goals were:

  • Usual: Less than 107mm Hg if 60 years of age or less and less than 113mm Hg if more than 60 years of age
  • Low: Less than 92mm Hg if 60 years of age or less and less than 98mm Hg if more than 60 years of age.

Patients with hypertension were identified at baseline by medical record review through documentation or use of medications. Medications were adjusted when blood pressure was not at goal or there were side effects.Angiotensin-converting enzyme inhibitors were recommended as the first therapy and calcium channel blockers were used as second therapy. Prescriptions for lifestyle modifications (sodium, weight, alcohol) by the MDRD study physicians based on medical and nutrition history, BMI, urine sodium or MAP.The priority for the MDRD Study was adherence to protein and phosphorus restriction rather than lifestyle modification.

Blinding Used

Not specified.

Intervention Used

Specified (above) levels of protein and phosphorus intake. Secondary interventions included lifestyle modifications. In this study the main interventions were sodium or weight modifications:

  • Sodium alone
  • Weight alone
  • Sodium plus weight. 

Statistical Analysis

Standard descriptive statistics (means, standard deviations) used for baseline and follow-up values for continuous variables. Chi-squared tests used to test associations between groups. Regression analysis completed in two-step manner to control for baseline MAP values when evaluating change in follow-up. Two-sided significance levels of 5% used.

Data Collection Summary:

Timing of Measurements

  • Blood pressure was taken monthly
  • Lifestyle intervention counseling started at the fifth visit after initiation of the low protein and low phosphorus diet portion of the study
  • Estimated sodium intakes were determined using 24-hour urine collection (visits five to 18)
  • Dietary intake was assessed using three-day food records two times at baseline and bimonthly thereafter
  • Physical activity questionnaires were administered at baseline and yearly thereafter to assess kcal expended per week.

Dependent Variables

Blood pressure.

Independent Variables

Protein and phosphorus intake.

Control Variables

  • Antihypertensive drugs
  • Lifestyle modifications
Description of Actual Data Sample:
  • Initial N: 724 subjects 
  • Attrition (final N): 693 subjects.

Age

  • All study participants: 53.1 years, with SD 10.7
  • By MAP group and lifestyle modification status (year, SD)
    • Usual MAP: Modification, 52.3(12.9)
    • Usual MAP: No modification, 52.5(11.9)
    • Low MAP: Modification, 50.0(13.2)
    • Low MAP: No modification.

Ethnicity

  • All study participants: 43.8% male
  • By MAP group and lifestyle modification status:
    • Usual MAP: Modification, 56.2% male
    • Usual MAP: No modification, 60.8% male
    • Low MAP: Modification, 39.2% male
    • Low MAP: No modification. 

Other Relevant Demographics

At baseline the GFR in the usual MAP group was 33.9ml per ml per minute per 1,73m2 and the low MAP was 34.6ml per minute per 1.73m2.

Anthropometrics

BMI was 29.4 and 28.6 for the groups of usual MAP and low MAP, respectively.

Location

15 US clinical centers (no more specifics given).  

Summary of Results:

Other Findings

  • 51.2% of patients were prescribed sodium or weight modification:
    • Sodium or sodium + weight loss: 31.2%
    • Weight loss: 20.0%
  • At baseline the sodium intake was 125.7mmol in the usual MAP group and 128.3mmol in the low MAP group. The baseline sodium urinary output was 162.0mmol per L in the usual MAP group and 1,643.8mmol per L in the low MAP group.Hypertensive patients with low MAP on sodium restrictions showed significant urine sodium reductions from baseline, P<0.01.
  • At 18 months, sodium restriction averaged 4.3mmol per L in the usual MAP group and 20.7mmol per L in the low MAP group
  • Weight loss averaged 2.0kg in the usual MAP group and 1.4kg in the low MAP group
  • Blood pressure decreased more in the low MAP group advised to low sodium or weight (–4.7±11.3 to –5.9±12.1mm Hg; P=0.0002). Patients in the weight loss + low sodium group showed the largest decrease in blood pressure (–7.4±11.4mm Hg; P=0.0002).
Author Conclusion:
  • Planned weight loss and modest sodium reductions were observed in hypertensive MDRD study subjects on concurrent dietary protein and phosphorus and antihypertensive medication interventions. Sodium or weight benefits were greater in those with hypertension randomized to the low MAP group and to the low protein group.
  • Even modest weight loss appeared beneficial for BP management. Weight loss benefits to blood pressure management would be important to confirm in future randomized studies in patients with renal disease and hypertension.
  • The sodium and weight reduction benefit was most pronounced in hypertensive subjects randomized to the low MAP and low protein (0.575g per kg per SBW). The larger benefit may have been related to the greater effort by MDRD health professionals with subjects following more stringent diets.
Funding Source:
Government: NIH, NIDDK
University/Hospital: University of Pittsburgh, Memorial Hospital of Rhode Island, Brown University School of Medicine, Vanderbilt University School of Medicine, Beth Israel Hospital
Reviewer Comments:

Small amounts of weight loss (less than 2kg) improved MAP by 4.7mm Hg. Sodium reductions reported in this study were approximately 500mg per day, resulting in decreased MAP by 5.9mm Hg.

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
  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
  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
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
  1. Was the research question clearly stated? Yes
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.1. 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
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? ???
2. Was the selection of study subjects/patients free from bias? ???
  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? No
  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? No
  2.2. Were criteria applied equally to all study groups? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
  3. Were study groups comparable? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  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
  3.4. 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
  3.5. 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
  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? No
4. Was method of handling withdrawals described? No
  4.1. Were follow-up methods described and the same for all groups? 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%.) No
  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%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? No
  4.4. Were reasons for withdrawals similar across groups? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? 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? No
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? ???
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? ???
  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.) No
  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.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  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
  5.4. 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
  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. 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
  6.1. 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
  6.2. 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
  6.3. 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
  6.4. 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? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments 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
  6.7. 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
  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. 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
  7.1. 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
  7.2. 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
  7.3. 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
  7.5. 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
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? 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. 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
  8.1. 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
  8.2. 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
  8.3. 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)? N/A
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  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
  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. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? 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. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes
  10.2. Was the study free from apparent conflict of interest? Yes