EAL

CKD: Sodium Requirements (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine the effect of sodium intake on the progression of renal failure.

Inclusion Criteria:

1. Patients followed for at least 7 months in an outpatient clinic for CRF at the University of Naples (Italy) between 12/1/84 and 12/31/96.

2. Creatinine clearance of 10-40 ml/min

3. Consuming <100 (LDS) or >200 (HDS) mEq of sodium/d based on urinary sodium constantly above or below these limits, and who had a neutral external sodium balance at each visit.

Exclusion Criteria:

1. Cardiac failure, liver disease or nephrotic syndrome.

2. Clinical evidence of volume depletion or fluctuating renal function.

3. Treatment with ACE inhibitors or diuretics.

Description of Study Protocol:

Recruitment: retrospective study of subjects followed between 12-01-1984 and 12-31-1996 in one renal clinic. A majority of patients included (75% HDS and 70% in LDS) were before 1992, when target BP value was higher.

Design: Cohort Study. Patients were evaluated at each clinic visit by a clinician and dietitian, the frequency determined by the degree of renal impairment.

1. Study diet:

a. kcal: 35-40 kcal/kg/d based on IBW and physical activity

b. protein: 0.6 g/kg/d + protein lost in urine (65- 85% of biological value)

c. phosphate: 6-9 mg/kgIBW/d

d. sodium: individualized to avoid sodium depletion and excessive extracellular volume expansion

e. diet individualized for each patient by the study dietitian

2. Biochemical data: collected at each clinic visit

a. 24-hr urine: urine protein, sodium and creatinine

b. blood: creatinine, phosphorus

Blinding Used (if applicable): Not used - lab tests.

Intervention (if applicable): Individualized study diets.

Statistical Analysis: All values reported as mean ± SEM. Paired and unpaired t-test used for intra- and inter-group comparisons, respectively.

Data Collection Summary:

Timing of Measurements: Unclear, alhtough reported to be similar. For LSD group, pateints were followed for 44± 8 months, with 11±2 visits. FOr HSD group, patients followed for 42 ±7 months, with 10± 2 visits.

Dependent Variables:

GFR
urine protein

Independent Variables:

kcal: 35-40 kcal/kg/d based on IBW and physical activity
protein: 0.6 g/kg/d + protein lost in urine (65- 85% of biological value)
phosphate: 6-9 mg/kgIBW/d
sodium: individualized to avoid sodium depletion and excessive extracellular volume expansion
diet individualized for each patient by the study dietitian

Control Variables: not specified.

Description of Actual Data Sample:

Initial N: 57 subjects met the criteria for study inclusion. The subjects were divided into 2 groups on the basis of urinary sodium: low sodium (LSD): <100 mEq/day or high sodium (HSD): >200 mEq/day

Attrition (Final N): 57 subjects

Age: 52 ± 2 (LSD), 48 ± 3 (HSD)

Ethinicity: not specified

Other relevant demographics:

Baseline Demographic data of subjects:
	LSD	HSD	p
Patients, n	27	30	-
Age, yr	52±2	48±3	NS
Male, %	59	83	-
Follow-up (months)	44±8	42±7	NS
Number of clinic visits	11±2	10±2	NS
Creatinine Clearance(ml/min)	24±2	28±2	0.02
MAP (mm Hg)	112±3	105±3	NS
Urinary protein excretion (g/d)	2.9±0.3	1.5±0.2	0.001

Anthropometrics: body weight: LSD males, 65.9 ± 2.1 kg; females 57.0 ± 4.0 kg. HSD males 70.1 ± 2.3; females 61.4 ± 7.1. No significant differences between groups.

Location: Naples, Italy

Summary of Results:

Differences between study groups at the end of the study:
Dietary protein intake (g/kg/d)	0.51±0.03	0.8±0.05
Urinary sodium excretion (mEq/d)	82±3	232±4	0.05
Urinary protein excretion (g/d)	1.9±0.3	2.4±0.4	0.005
GFR (ml/min/month)	0.25±0.97	0.51±0.09	0.05

An improvement in renal outcome was detected in patients undergoing salt restriction

Author Conclusion:

The present study, although with the limits intrinsic to a retrospective analysis, suggests that efficacious salt restriction in CRF patients per se improves outcome of renal disease with a decline in GFR and proteinuria independent of antihypertensive effects.

Since a lower intake of sodium was found to be coupled with a greater adherence to the prescribed low protein diet, it is impossible to determine whether the low protein intake contributed to the protective effects of the low salt diet.

These data stress the importance of the assessment of urinary sodium output when examining the impact of a low protein diet or other interventions aimed at delaying the progression of CRF. We recommend prospective clinical trials to evaluate the pathophysiological role of salt intake in CRF.

Funding Source:

University/Hospital:

University of Naples 'Federico II'

Reviewer Comments:

A limitation of this study is that it cannot show cause and effect. Also, it is impossible in this type of study to determine if the low protein diet or low sodium diet was responsible for the slower progression of decline in GFR in the low salt/low dietary protein group.

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?		???
	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?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
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)	N/A
	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.)	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?	???
	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?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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?	N/A
	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?	No
	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?	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?	???
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	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
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?	N/A
	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?	No
	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)?	???
	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes