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CKD: Hyperphosphatemia (2010)


Kates DM, Sherrard DJ, Andress DL.  Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure.  Am J Kidney Diseases 1997;30:809-813.


Worksheet created prior to Spring 2004 using earlier ADA research analysis template.
PubMed ID: 9398125
Study Design:
Cross-Sectional Study
D - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To determine whether there was an association between serum phosphate and circulating calcium, PTH and/or 1,25-dihydroxyvitamin D.
Inclusion Criteria:

1. Unrestricted diet

2. Pre-dialysis

Exclusion Criteria:

1. Diseases other than CRF that would affect calcium, phosphate, vitamin D or PTH metabolism.

2. Taking calcium supplements

3. Taking vitamin D supplements

4. Taking phosphate binders, steroids or anticonvulsant medications

Description of Study Protocol:


84 patients with CRF were recruited from the outpatient clinics at the Seattle VA Medical Center and the University of Washington.

Design:  Cross-Sectional Study

Blinding Used (if applicable):  not applicable

Intervention (if applicable):  not applicable

Statistical Analysis:

Statistical analysis was done using ANOVA. Subjects were placed into 6 groups based on serum creatinine:

Group 1. 1.2-1.6 mg/dL (n=14)

Group 2. 1.7-2.0 mg/dL (n=14)

Group 3. 2.1 -3.0 mg/dL (n=16)

Group 4. 3.1-5.0 mg/dL (n=17)

Group 5. 5.1-7.0 mg/dL (n=14)

Group 6. >7.0 mg/dL (n=9)

Data Collection Summary:

Timing of Measurements:

Blood was drawn after a morning fast for biochemical measurements in serum: creatinine calcium phosphate Intact PTH 25(OH) vitamin D 1,25(OH)2 vitamin D

Dependent Variables:

  • Serum phosphate
  • Serum PTH

Independent Variables

  • 24-hr urine was used for biochemical measurements of creatinine
  • Subjects were placed into 6 groups based on serum creatinine:

    Group 1. 1.2-1.6 mg/dL (n=14)

    Group 2. 1.7-2.0 mg/dL (n=14)

    Group 3. 2.1 -3.0 mg/dL (n=16)

    Group 4. 3.1-5.0 mg/dL (n=17)

    Group 5. 5.1-7.0 mg/dL (n=14)

    Group 6. >7.0 mg/dL (n=9)

Control Variables

Description of Actual Data Sample:

Initial N:

84 patients with CRF were recruited from the outpatient clinics at the Seattle VA Medical Center and the University of Washington.

Attrition (final N):  84

Age:  see Results

Ethnicity:  not mentioned

Other relevant demographics:

Anthropometrics:  The characteristics of the patients were not different by study group except that the majority of the subjects were male.

Location:  Washington

Summary of Results:
































Only 57 (68%) were able to provide 24-h urine for determination of creatinine clearance.

Serum biochemistries by group:








































*P<0.05 vs. group 1

** normal ranges






Using stepwise regression analysis after adjusting for multiple comparisons, we found that serum phosphate correlated directly with serum PTH (r=0.62, P<0.01) in patients with mild to moderate CRF (creatinine <3.0 mg/dL), independent of serum calcium and 1,25(OH)2 D levels. In patients with more severe CRF (creatinine >3 mg/dL), only serum calcium correlated with serum PTH (r=0.47, P<0.01). Serum 1,25(OH)2 in patients with mild CRF was lower than that in age-matched controls (24±3 pg/mL vs. 37±2 pg/mL; P<0.01).

Author Conclusion:

These data demonstrate an independent association of serum phosphate with PTH in patients with mild to moderate CRF and suggest that phosphate may directly enhance PTH secretion in this setting.

Our results suggest the need for early restriction of phosphate intake before serum phosphate exceeds normal levels or before serum creatinine exceeds 3.0 mg/dL.


Funding Source:
Government: Department of Veterans Affairs,
University/Hospital: VA Administration Medical Center, University of Washington, Nichols Institute
Foundation associated with industry:
Reviewer Comments:

Although this study is cross-sectional and cannot demonstrate cause and effect, the results suggest that increased serum phosphate is a marker for early renal failure and is directly correlated with increased PTH and becomes evident when serum creatinine is~3 mg/dL and creatinine clearance is ~30 mL/min.

Secondary hyperparathyroidism should be avoided to prevent metastatic calcification of body tissues.

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) N/A
  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) N/A
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) 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? Yes
  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.) Yes
  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? Yes
  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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? 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? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? 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
  7.1. 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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  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