EAL

Chronic Kidney Disease and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the effects of phosphorus supplementation for 15 days on mineral metabolism in patients with successful kidney allografts.

Inclusion Criteria:

Subjects with kidney transplant; stable allograft function with serum creatinine consistently less than 2.0mg per dL and phosphate equal or less than 3.5mg per dL at the time of the study.

Exclusion Criteria:

None except not meeting all inclusion criteria.

Description of Study Protocol:

Recruitment

The study was performed during January and February 1997. However, there is no mention as to how patients were recruited.

Design

Kidney transplant recipients with 41±18 months of transplantation took part in the study. After a wash-out period of one month in which oral phosphorus supplementation was discontinued, biochemical parameters were measured in the baseline period (FO period). Then patients received 1.5g per day of oral phosphorus for 15 days, and the same parameters were determined (F1 period). Blood and 24-hour urine were collected for the measurements of all biochemical parameters. All patients were advised to continue with their habitual diets during these 15 days. All of them were on triple immunosuppressive therapy. None of them received allopurinol, anticonvulsants, vitamin D supplements, antacids or other drugs.

For data analysis, patients were divided into two subgroups according to allograft function; optimal group with a creatinine clearance of more than 70ml per minute per 1.73m²and an suboptimal group with a CrCl ranging between 46ml and 69ml per minute per 1.73m².

Intervention

Oral phosphorus, 1.5g per day (750mg tablet each).

Statistical Analysis

Paired T-test was used for before and after the supplementation, and T-test for comparisons between subgroups. The correlation between continuous variables was measured by Pearson's test. Stepwise multiple linear regression was utilized to establish the best determinants over the PTH changes after supplementation. P<0.05 was considered to be statistically significant.

Data Collection Summary:

Timing of Measurements

Biochemical parameters from blood and urine samples were determined at baseline and after 15 days of oral phosphorus supplementation.

Dependent Variables

PTH
Serum bicarbonate
25 hydroxycholecalciferol
1,25 dihydroxycholecalciferol
Uric acid
Total calcium corrected to albumin
Phosphate
Alkaline phosphatase
Serum bicarbonate
Creatinine
Creatinine clearance.

Independent Variables

Oral phosphate.

Description of Actual Data Sample:

Initial N: 32 (15 females, 17 males)
Attrition (final N): 32 (15 females, 17 males)
Age: Mean age, 50+12
Other relevant demographics: Only three patients received diuretics (furosemide 40mg per day). The PTH concentrations obtained immediately before kidney transplantation were available in all patients. None of the patients had acute or chronic inflammatory, infectious, tumoral or liver disease, diabetes or proteinuria greater than 1.0g per 24 hours.
Anthropometrics: No measurements
Location: Badajoz, Spain.

Summary of Results:

Biochemical Characteristics for the Whole Group at Baseline (F0) and After Phosphorus Supplementation (F1)

Variables	F(0)	F(1)	Statistical Significance of Group Difference
Serum creatinine (mg per dL)	1.23±0.34	1.23±0.34	INS
Creatinine clearance (ml per minute per 1.73m ²)	79±21	82±22	NS
Serum calcium (mg per dL)	10.53±0.9	10.23±0.7	0.0003
Serum phosphatase (mU per ml)	2.62±0.58	3.37±80	0.0001
Serum bicarbonate (mEq per L)	24.6±1.5	23.8±1.7	0.0025
PTH (pg per ml)	132±97	172±138	0.0001
1,25(OH)₂D (pg per ml)	40.5±15.9	33.8±12.8	0.0006
Urinary calcium (mg per 24 hours)	189±10.6	122±72	0.0001
Urinary phosphorus (mg per 24 hours)	824±332	1,668±478	0.0001

In the F0 period, PTH concentrations correlated with pre-transplant PTH concentrations (R=0.67; P<0.0001), but not with the time elapsed since transplantation.

Other Findings

Patients with optimal allograft function (CrCl more than 70ml per minute per 1.73m²) had significantly lower PTH (P<0.05) and higher 1,25(OH)2D (P<0.05) concentrations than patients with suboptimal allograft function (CrCl = 46 to 69ml per minute per 1.73m²) at baseline
After phosphorus supplementation changes in 1,25(OH)2D, expressed as the percentage of the initial concentration, correlated positively with the percentage changes in PTH concentrations for whole group and subgroup.

Author Conclusion:

Oral phosphorus supplementation led to a significant increase in PTH concentration of kidney transplant recipients. This observation suggests that phosphorus administration should be avoided after kidney transplantation as much as possible.

Funding Source:

Other:

No data

Reviewer Comments:

The study does not consider the content of phosphorus in the diet, nor does it look at nutritional status. The small sample increases the risk for type two error. Table 2 is confusing due to the lack of legends.

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)	No
	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?		No
	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?	No
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?		???
	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%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	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?	???
	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?	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
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?	N/A
	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
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	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?	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?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	No
	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?	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)?	No
	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?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???