EAL

CKD: Hyperphosphatemia (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine the relationship between creatinine clearance and iPTH in patients with renal insufficiency.

Inclusion Criteria:

1. Renal impairment

2. Not on chronic dialysis

Exclusion Criteria:

1. Taking medications that might alter iPTH (vitamin D, estrogens)

2. Liver dysfunction

Description of Study Protocol:

Recruitment

Patients were recruited from outpatient Renal and Endocrine clinics at the Brigham and Women’s Hospital, Boston. Patients were recruited for the study during routine clinic visits.

Design: Cross-Sectional Study

Blinding Used (if applicable): not applicable

Intervention (if applicable): not applicable

Statistical Analysis:

Kruskal-Wallis test for populations with nonparametric distributions was used to determine significance of differences among groups. Correlation analysis was used to evaluate a relationship between pairs of variables, and multiple regression was used to determine the influence of several variables on iPTH and alkaline phosphatase.

Data Collection Summary:

Timing of Measurements:

Blood samples were taken between 9 a.m. and 12 noon. for assays for iPTH, n-terminal PTH, 25(OH)D, and 1,25(OH)2D, creatinine, phosphate, alkaline phosphate, and routine chemistries.

Dependent Variables

iPTH, n-terminal PTH, 25(OH)D, and 1,25(OH)2D, creatinine, phosphate, alkaline phosphate, and routine chemistries
24-hr urine collections for creatinine clearance
Radiographs of clavicles, hands, spine and pelvis for identifying renal osteodystrophy

Independent Variables

Patients consumed usual diet prior to the study

Control Variables

Description of Actual Data Sample:

Initial N:

66 patients were screened for the study, 7 were excluded based on criteria.

Attrition (final N): 59 subjects (21 men and 37 women) participated in the study. 39 subjects collected 24-hr urines and 29 subjects had radiographs.

Age: aged 20 - 81 years

Ethnicity: not mentioned

Other relevant demographics:

Anthropometrics:

Location: Massachusetts

Summary of Results:

Causes of kidney disease in subjects:
	%
Hypertension	57.6
Diabetes	22.0
Hypertension + Diabetes	18.6

Medications:
	%
Phosphate binders
Calcium carbonate	23.7
Aluminum binders	3.3
Calcium channel blockers	25.4
Furosamide	13.5
ß- blockers	16.9
Ace inhibitors	13.5

Relationship between iPTH and creatinine clearance: Analysis of parameters of bone metabolism by groups based on severity of kidney disease: Effects of kidney disease on bone:

**Comparison of metabolic parameters by severity of renal insufficiency:**
	Mild	Moderate	Severe
	n=13	n=14	n=18
CrCl (ml/min)	81±5	44±3	10±1
IPTH (pg/ml)	37±5	95±29	271±43
Calcium (mg/ml)	9.3±0.2	9.1±0.2	8.6±0.2
Phosphate (mg/ml)	3.5±0.1	3.7±0.2	5.3±0.4
1,25 D (pg/ml)	38±9	29±5	11±4
Alk-phos (IU/L)	88±6	97±6	144±15

Serum alkaline phosphatase activity was very tightly correlated with iPTH levels (r=0.77, P<0.001) and less tightly correlated with creatinine clearance (r=-0.43, P<0.01). Using multiple regression analyses, iPTH was the only variable contributing independently to changes in alkaline phosphatase. No patients with mild renal insufficiency had positive radiographs and 2 out of the 22 with severe renal disease showed renal osteodystrophy.

IPTH, alkaline phosphatase activity and serum phosphate were significantly increased in the group with severe renal failure as compared with the 2 other groups (P<0.01) while 1,25(OH)2D was significantly decreased in those with severe renal disease compared with the mild and moderate renal insufficiency groups.

The single most important determinant of iPTH was renal function. By simple regression analysis, iPTH correlated equally well with both creatinine clearance and serum creatinine. Creatinine clearance: (r=0.60, P<0.001) Serum creatinine: (r=0.52, P<0.001); iPTH increased above normal range (10-65 pg/ml) when the creatinine clearance decreased to 60 ml/min. Serum calcium and phosphate showed weaker, but still significant correlation with iPTH levels (calcium, r= - 0.39, P<0.01; phosphate, r = 0.31, P<0.05).

Author Conclusion:

Intact PTH (iPTH) can be elevated in patients with milk to moderate renal insufficiency, thus efforts to prevent the development of secondary hyperparathyroidism in renal failure should be undertaken early in the course of renal insufficiency.

We found iPTH levels to be increased in nonnephrotic patients with mild to moderate renal failure, before abnormalities in serum calcium, phosphate, or vitamin D became apparent. Since iPTH is less dependent on renal function for its clearance than both active and inactive PTH fragments, these observations represent parathyroid hypersecretion in patients with mod to moderate renal insufficiency. Studies are needed to determine the pathogenesis of hyperparathyroidism in early renal disease.

Funding Source:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Since this study was cross-sectional, the results do not demonstrate cause and effect. However, the results are consistent with other studies in that as creatinine clearance begins to decrease below 60 ml/min, there are changes in metabolic parameters related to calcium and bone metabolism.

As CrCl decreases below 60 ml/min, iPTH increases, serum phosphate increases, and serum calcium decreases.

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?		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?		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
	3.3.	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
	3.5.	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?	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?	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