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CKD: Sodium Requirements (2010)

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

To examine type 2 diabetic patients with early nephropathy and normal levels of serum creatinine and determine whether sodium sensitivity of blood pressure appears before hypertension begins and whether the sensitivity was related to albuminuria during two weeks.

Inclusion Criteria:

Diabetes type 2 with early nephropathy.

Exclusion Criteria:
  • Non-diabetic renal disease
  • Heart disease
  • Urinary tract infection
  • Serum creatinine of greater or equal to 1.1mg/dL
  • Anti-hypertensive drugs.
Description of Study Protocol:

Recruitment

Patients were selected randomly.

Design

Patients were divided into three groups by their level of albuminuria; normoalbuminuria, microalbuminuria and macroalbuminuria. Patients were either on a diet with a low or ordinary sodium level for one week at each sodium intake, in a random order. The calories (30kcal per kilogram) and the amount of protein intake (1.2g per kilogram per day) were kept  constant. On the last day of each regimen, 24-hour urine collection was performed. On the last day of the diet with an ordinary sodium level, renal plasma flow was measured. Biochemistry parameters were measured at the end of each regimen. Only insulin and oral antihyperglycemic agents were used. 

Intervention

  • Low sodium diet: Approximately 80mmol per day
  • Ordinary sodium diet: Approximately 200mmol per day.

Statistical Analysis

For plasma renin activity, urinary excretion of albumin, and the sodium sensitivity index (SSI), values were expressed as medians with the 25th and 75th percentiles. Anova was used to compare the characteristics of the patients at the start of the study and for the SSI among the three groups followed by Scheffe's test and Kruskal-Wallis test, respectively, when statistical differences were found. The significance of differences during the two diets were examined with Student's T-test for paired samples or Wilcoxon's signed-rank test. The correlation coefficients for urinary excretion of albumin on the diet with the ordinary sodium level with the SSI or mean arterial pressure (MAP) were calculated by the least-squares method. A difference with P<0.05 was considered to be significant.

Data Collection Summary:

Timing of Measurements

Sodium, creatinine and albumin urinary were collected during 24 hours during the last three days of each diet. The renal clearance of creatinine and plasma renin activity were measured at the last day of each diet; and the renal plasma flow was measured on the last day of the diet with an ordinary sodium level.

Dependent Variables

  • Systolic and diastolic blood pressure (mmHg) 
  • Urinary sodium excretion (mmol per day) 24 hours of urine
  • Urinary albumin (milligrams per day)
  • Plasma renin activity(ng per ml per hour)
  • BMI (kg).

Independent Variables

  • Low sodium diet
  • Ordinary sodium diet.

Control Variables

  • Gender
  • Age
  • SSI-slope of the pressure-natriuresis curve (urinary sodium excretion as a function of MAP); it reflects sodium sensitivity of the blood pressure
  • Creatinine clearance (milliliters per minute/1.73m2)
  • Renal plasma flow (milliliters per minute/1.73m2).
Description of Actual Data Sample:

Initial N

32; (59% males, 41% females) 

Attrition (final N)

32; (59% males, 41% females) 

Age

Mean age 60.6±9.3

Ethnicity

Japanese

Other relevant demographics

Plasma glucose levels were brought under control during two weeks of hospitalization before the study was performed. All patients had simple rethinopathy. 11 patients had normoalbuminuria; 12 microalbuminuria and nine macroalbuminuria. Serum creatinine was higher between patients with macroalbuminuria.

Anthropometrics

BMI was well matched between groups

Location

Osaka City General Hospital; Japan

 

Summary of Results:

 Characteristics of diabetic patients at the start of the study

 

Patients with normoalbuminuria (N=11)

Patients with microalbuminuria (N=12)

Patients with macroalbuminuria (N=9)
BMI (kg) 22.0+2.1 24.4+4.4 22.8+4.3
Fasting plasma glucose (mmol/l) 6.81+0.94 6.74+0.71 7.19+1.00
HbA1c (percentage) 8.6+1.1 8.1+1.8 8.5+1.6
Serum creatinine (mmol/l) 53.8+13.9 60.4+13.5 72.7+16.4*
Systolic blood pressure (mmHg) 132+11 136+9 144+8**
Diastolic blood pressure (mmHg) 73.7+7 82+6& 85+7#

 

 

 

 

 

 

 

* P=0.025; ** P= 0.024; & P =0.016; # P= 0.0012  vs. patients with normoalbuminuria

Other Findings

  • The SSI and MAP were higher in micro and macroalbuminuric patients than in normoalbuminuric patients; P<0.001.
  • With an ordinary level of sodium intake, 18 patients had normal systemic pressure (<140/90mmHg) and among them, 10 patients had blood pressure less than 130/85mmHg. For these 10 patients, the index in those with albuminuria was higher than in those with normoalbuminuria; P<0.011.
  •  Only patients without hypertension, on diet with ordinary salt level, the albumin excretion was correlated with SSI (r=0.67; P<0.0016) but not MAP (r=0.40). 
  • In patients without hypertension but with albuminuria, the blood pressure and albumin excretion were decreased by sodium intake restriction; P<0.02.

 

 

Author Conclusion:

In type 2 diabetic patients with albuminuria but normal serum creatinine levels,sodium sensitivity of blood pressure appears before hypertension and is related to albuminuria. Restriction of sodium intake is one treatment of early diabetes nephropathy, even without hypertension.

Funding Source:
University/Hospital: Osaka City General Hospital for medical research, Japan
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

There is washout period between the two diets. Short period of follow-up.

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) ???
  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? No
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) Yes
  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? 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%.) N/A
  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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? 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.) 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? ???
  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? No
  6.6. Were extra or unplanned treatments described? No
  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? ???
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? ???
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. 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? No
9. Are conclusions supported by results with biases and limitations taken into consideration? No
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
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