EAL

CKD: Hyperphosphatemia (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purposes of this study were to determine:

1) the distribution of the types of renal osteodystrophy in both the predialysis and dialysis population in a single geographic area.

2) the correlation between PTH and bone histology in both increased and decreased turnover bone disease in predialysis and dialysis patients.

3) whether dialysis improves the bone response to PTH.

4) whether differences in bone histology and the bone response to PTH are present between CAPD and hemodialysis patients.

Inclusion Criteria:

1. Every patient evaluated for maintenance dialysis or had received maintenance dialysis for >8 months were eligible for the study.

Exclusion Criteria:

1. Parathyroidectomy

2. Anephric

3. Receiving steroid or anticonvulsant

Description of Study Protocol:

Recruitment

The study was done in two hospitals located in the Canary Islands from October 1988 to January 1991.

Design: Cross-Sectional Study

Blinding Used (if applicable): not applicable

Intervention (if applicable): not applicable

Statistical Analysis:

Linear regression analysis was used to correlate PTH levels with bone histologic parameters. Partial correlation analysis was used. Chi-square or Fisher's test were used to compare 2 independent proportions. Comparison between parameters from 2 different groups were performed using unpaired t test. One-way ANOVA follow by Newman-Keuls test was used to assess differences between more than 2 means.

Data Collection Summary:

Timing of Measurements

Bone biopsies were performed after in vivo double tetracycline labeling. Biochemical parameters: Blood samples were taken after an overnight fast during the same week as the bone biopsy; calcium, phosphorus, alkaline phosphatase and intact parathyroid hormone (PTH) were measured.

Dependent Variables:

Bone histomorphometric parameters
Blood samples were taken after an overnight fast and analyzed for calcium, phosphorus, alkaline phosphatase and intact parathyroid hormone (PTH)

Independent Variables

The concentration of the dialysate was 7 mg/dl and the aluminum concentration in the dialysate was <10 µg/L.
Calcium carbonate was used as the primary phosphate binder; aluminum hydroxide was added only if calcium carbonate was not tolerated or did not adequately control serum phosphorus (>5.5 mg/dl)
6 hemodialysis and 12 CAPD patients had received oral 1 a -OHD3 (0.5 µg/d) during the 6 months prior to the bone biopsy; none of the predialysis patients had received vitamin D.

Control Variables

Description of Actual Data Sample:

Initial N: 149 subjects were eligible for the study and 119 (80%) volunteered for the study. 38 subjects were immediately predialysis and had creatinine clearances <10 ml/min/1.73 m2.

Attrition (final N): 119 volunteers.

Age: see Results

Ethnicity: not mentioned

Other relevant demographics:

Anthropometrics:

Location: Spain

Summary of Results:

Patient characteristics:
	Predialysis	HD	CAPD
	n=38	n=49	n=32
Age, yr	47±16	45±16	48±12
Male, %	60.5	71.4	68.7
Diabetic,%	13	10	21
Dialysis, duration (months)	-	41±38	15±4
Serum biochemistries: Calcium, (mg/dL)	8.11±0.82	9.31±0.83a	9.54±0.60c
Phosphorus, (mg/dL)	6.37±1.37	6.06±1.46	4.61±1.07ad
HCO3, (mEq/L)	20.7±3.2	21.3±2.8	21.8±1.9
ALP, (IU/L)	238±109	454±869	260±240
PTH, (pg/mL)	421±413	437±474	273±315
aP<0.01 vs. predialysis
cP<0.001 vs. predialysis
dP<0.02 vs. predialysis

Aplastic bone disease with <5% bone surface aluminum was a common finding (48%, 32% and 48%, in preD, HD, and CAPD respectively). The next most common type of bone disease was osteitis fibrosa followed by mild hyperparathyroidism and then osteomalacia. The distribution was similar among the study groups except for osteomalacia with a very small percentage in the predialysis group.

In all groups, PTH <120 pg/ml was highly predictive of low bone turnover.

Conversely, a PTH level >450 pg/mol was always associated with histologic features of hyperparathyroid bone disease.

The range of PTH needed to obtain a normal osteoblast surface of 1.5% was greater in predialysis than HD or CAPD (300 to 500 vs. 75 to 260 pg/ml, respectively).

Author Conclusion:

Aplastic bone disease without significant bone surface aluminum was a common finding in our predialysis, hemodialysis, and CAPD patients. Maintenance dialysis improved the bone response to PTH. Finally, the results of our study help define a range of intact PTH levels that would be desirable in order to avoid both aplastic bone disease and significant hyperparathyroid bone disease.

Funding Source:

Government:

CAICYT

Reviewer Comments:

Although this study was observational, the data shows a positive association between intact PTH and aplastic bone disease.

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)?	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
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