CKD: Hyperphosphatemia (2010)

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

The purpose of this study was to assess the long-term effects on phosphate and calcium metabolism of a low phosphorus diet (5-7 mg/kg/IBW/day) and low protein diet (0.4 g/kg/IBW/day supplemented with keto and amino acids), and 400 to 800 mg calcium carbonate/day and 1000 IU vitamin D2/day.

Inclusion Criteria:

1.  GFR < 20 ml/min

2.  Follow-up data available for 2 years

3.  Compliant to study diet (+20%)for dietary protein as determined by dietary interviews and urinary nitrogen.

Exclusion Criteria:

1. Diseases altering calcium and phosphate metabolism.

2. Use of medications: steroids, anticonvulsant drugs, calcium supplements, aluminum containing antacids or other phosphate binders.

Description of Study Protocol:

Recruitment

Ambulatory patients with advanced renal failure were retrospectively selected for the study because of the duration of their follow-up and their good compliance with the dietetic prescriptions.

Design:  Cohort Study

Blinding Used (if applicable):  not applicable

Intervention (if applicable):

Study diet:

a. 0.4 g protein of vegetable origin /kg, 5-7 mg phosphorus/kg and 300 mg calcium and supplemented with essential amino acids and ketoanalogues to provide 75 mg nitrogen and 3.4 mg calcium/ 5 kg body weight.

b. 35 kcal/kg/d; 67% carbohydrate, 30% fat, 3% protein

c. calcium carbonate: 1-2 g/d to maintain serum calcium between 2.1 and 2.5 mmol/L.

d. iron and multiple vitamin with 1,000 IU vitamin D2/day.

Statistical Analysis

The effect of low-protein diet on different parameters with time was evaluated by one-way ANOVA.  Multiple regression analysis was applied to correlate the concentrations of intact plasma PTH with several variables.  Linear regression analysis was used to determine the correlation between two variables.

 

 

Data Collection Summary:

Timing of Measurements

Before the study and monthly data: 24-hr urine for creatinine, urea, calcium, phosphate and fasting (plasma) creatinine, urea, calcium, phosphate, bicarbonate, alkaline phosphatase, osteocalcin, intact-parathyroid hormone (PTH).  Before the study, and after 12 and 24 months, blood samples were taken during the same season of the year for determinations of calcidiol and calcitriol.  GFR evaluated every 3 months based on clearance of 51Cr-EDTA from plasma and urine samples.

Dependent Variables

  • Intact-PTH
  • Total calcium
  • Serum phosphorus

Independent Variables

Study diet:

a. 0.4 g protein of vegetable origin /kg, 5-7 mg phosphorus/kg and 300 mg calcium and supplemented with essential amino acids and ketoanalogues to provide 75 mg nitrogen and 3.4 mg calcium/ 5 kg body weight.

b. 35 kcal/kg/d; 67% carbohydrate, 30% fat, 3% protein

c. calcium carbonate: 1-2 g/d to maintain serum calcium between 2.1 and 2.5 mmol/L.

d. iron and multiple vitamin with 1,000 IU vitamin D2/day.

Compliance to study diet assessed by diet interviews and 4-day food records every 3 months and month measurement of urinary urea and phosphorus excretion.

Control Variables

Description of Actual Data Sample:

Initial N:  29 patients had complete data for study inclusion

Attrition (final N):  29

Age:  see table

Ethnicity:  see table

Other relevant demographics:

Demographic data:

Variable

 
Age, years 56.1 +/- 13.4

Male, %

68.9

Causes of CKD, %

 

Glomerulonephritis

17.2

Chronic pylonephritis

20.7

Polycystic kidney

17.2

Benign nephrosclerosis

17.2

Anthropometrics:

Location:  France

 

Summary of Results:

Evaluation after 2-yr of study:
  0 2 yr P

GFR, ml/min

13.7±4.5

11.1±3.7

0.0001

Urine urea (mmol/24-hr)

209±74

96±36

0.0001

Urine phosphorus (mmol/24-hr)

16.5±4.9

7.2±3.4

0.0001

Ionized calcium (mmol/L)

1.21±0.15

1.27±0.14

NS

Serum phosphorus (mmol/L)

1.57±0.33

1.32±0.24

0.001

Serum bicarbonate (mmol/L)

23.5±2.6

23.8±2.5

NS

Intact-PTH (pg/ml)

144±95

88±78

0.01

Calcitriol (pg/ml)

15.4±4.5

14.6±4.1

NS

Alkaline phosphatase (IU/L)

85.1±29.9

68.1±22.2

0.005

Osteocalcin (pg/ml)

48.6±31.1

39.7±3.6

0.01

Albumin (g/L)

38.7±3.5

39.7±3.6

NS

Other Findings

At the start of the study, biologicval evidence of hyperparathyroidism (HPT) was present with increased plasma PTH (144+95 mg/ml), increased plasma phosphorus (1.57+0.33 mmol/L), an increase in alkaline phosphatase activity and plasma osteocalcin. Plasma PTH was positively correlated with plasma phosphorus and inversely with calcium and GFR. Phosphorus and protein restriction induced a significant correction of HPT within 3 months after starting the diet.

After 2 yr on the diet, despite the decrease in GFR, plasma PTH was still lower than at the start of the diet (88+57 pg/ml P<0.01) as was plasma phosphorus (1.32+0.24 mmol/L, P<0.001), total calcium higher (P<0..01).

Author Conclusion:

The results of the present study suggest that phosphorus and protein restriction with calcium supplementation and without calcitriol supplementation in patients with advanced CKD may induce a lasting correction of HPT, potentially mediated by the decrease of plasma phosphorus and increase in plasma calcium independent of plasma calcitriol.

Funding Source:
University/Hospital: Hopital Pelegrin, Hopital Universitaire d'Amiens (France)
Reviewer Comments:

Vitamin D was measured in only 14 patients. The concentration of vitamin D was below the normal range.

A diet low in phosphorus(~360 to 480 mg/d), supplemented with 1-2 g calcium and 1,000 IU vitamin D2 prevented the development of HPT in this retrospective study.

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? 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
  2.2. 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? N/A
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  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? N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? 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? Yes
4. Was method of handling withdrawals described? Yes
  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%.) 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
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.4. 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
  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. 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
  5.1. 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
  5.2. 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? Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  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? 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? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  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? ???
7. Were outcomes clearly defined and the measurements valid and reliable? ???
  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
  7.4. 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? No
  7.7. Were the measurements conducted consistently across groups? No
  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? ???
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  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? No
  9.2. Are biases and study limitations identified and discussed? No
  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