Educational Strategies to Reduce Serum Phosphorus in Hyperphosphatemic Patients With Chronic Kidney...

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REVIEW

Educational Strategies to Reduce SerumPhosphorus in Hyperphosphatemic PatientsWith Chronic Kidney Disease: SystematicReview With Meta-analysisDaniel Caldeira, MD,* Tiago Amaral, MD,† Cl�audio David, MD,*‡

and Cristina Sampaio, MD, PhD*§

Objective: To systematically review educational strategies for phosphorus reduction in patients with hyperphos-

phatemia and chronic kidney disease (CKD).

Design: Systematic review with meta-analysis.

Data Sources: CENTRAL, MEDLINE, EMBASE, and mRCT databases were assessed in June 2010.

Study Selection: Randomized controlled trials evaluating educational strategies related to diet in hyperphospha-

temic patients with CKD.

Data Extraction and Synthesis Method: Study characteristics, phosphorus levels, and calcium–phosphorus

product levels were retrieved. Jadad scale was used for quality assessment. Mean difference (MD) and 95% confi-

dence intervals (CIs) were calculated by random effects method.

Results: Seven randomized controlled trials were retrieved with a total of 524 patients with hyperphosphatemia

and CKD. Educational strategies reduced phosphorus levels with an MD of 20.72 mg/dL (95% CI: 21.11 to

20.33, P, .01). Sensitivity analysis of trials with follow-up of,4months did not show any benefit of the intervention,

but educational intervention for $4 months showed an MD of 21.07 (95% CI: 21.49 to 20.64, P , .01). Calcium–

phosphorus product level was improved in 227 evaluated patients from 5 trials with an MD of 25.22 mg2/dL2

(95% CI: 29.48 to 20.98, P 5 .02, and I2 5 58%). Sensitivity analysis removed the source of heterogeneity and re-

sulted in an MD of 23.02 (95% CI: 26.51 to 0.47, P 5 .09).

Conclusions: Education helped reduce phosphorus levels in hyperphosphatemic patients with CKD, particularly

those on dialysis.

� 2011 by the National Kidney Foundation, Inc. All rights reserved.

PATIENTS WITH CHRONIC kidney dis-ease (CKD) often have impairment of min-

eral metabolism, and phosphorus levels increaseas the disease advances.1,2 Hyperphosphatemiais associated with increased mortality3,4 andmorbidities such as high turnover bone disease5

and hyperparathyroidism.6 Increased serum phos-phorus level is also associated with progression ofCKD.7 Elevated calcium–phosphate (Ca 3 P)product level is related to calciphylaxis.8

Hyperphosphatemia management includes die-tary restriction, use of phosphate-binding agents,and dialysis.9

Patients’ knowledge about high-phosphoruscontaining food and compliance to an adequatediet regimen are essential to maintain phosphorus

*Clinical Pharmacology and Therapeutics Laboratory, Faculty of

Medicine, Lisbon, Portugal.

†Nephrology Department, Hospital Santa Cruz, Centro Hospi-

talar Lisboa Ocidental, Lisbon, Portugal.

‡Department of Cardiology, Hospital Santa Maria, Centro Hos-

pitalar Lisboa Norte, Lisbon, Portugal.

§Neurological Clinic Research Unit, Institute of Molecular Med-

icine, Lisbon, Portugal.

This research received no specific grant from any funding agency in

the public, commercial or not-for-profit sectors.

Address reprint requests to Daniel Caldeira, MD, Laborat�orio deFarmacologia Cl�ınica e Terap̂eutica, Faculdade de Medicina da Uni-

versidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028,

Portugal. E-mail: [email protected]� 2011 by the National Kidney Foundation, Inc. All rights

reserved.

1051-2276/$36.00

doi:10.1053/j.jrn.2010.11.006

Journal of Renal Nutrition, Vol 21, No 4 (July), 2011: pp 285–294 285


in acceptable levels. Previous studies suggested thatpatient education may improve phosphate con-trol.10,11 Certain techniques, such as educationalprograms or nutritional counseling, may improvehyperphosphatemia and its complications.

The objective of this review is to assess theefficacy through randomized controlled trials(RCTs) of educational and/or nutritional coun-seling to decrease phosphorus and Ca 3 P prod-uct levels in patients with hyperphosphatemiaand CKD.

Methods

Searching

A searching strategy was developed using CEN-TRAL (Cochrane Library issue April 2010),MEDLINE (until June 2010), and EMBASE(until June 2010) databases for identification ofRCTs. Database mRCT (June 2010) was alsosearched for completed and/or unpublished clini-cal trials. The following termswere used and com-bined with Boolean operators AND and OR:‘‘education*,’’ ‘‘counsel*,’’ ‘‘phosphorus,’’ ‘‘phos-phate,’’ ‘‘hyperphosph*,’’ ‘‘chronic,’’ ‘‘end-stage,’’‘‘renal,’’ ‘‘kidney,’’ ‘‘failure,’’ ‘‘injury,’’ ‘‘dialysis,’’and ‘‘hemodialysis.’’ No language limitation wasapplied. Articles references were also searched inan attempt to identify any missing study.

Selection

Search method was developed to obtain RCTsassessing educational interventions to reducephosphorus levels in patients with CKD andhyperphosphatemia. We included all patientswith CKD considered to be hyperphosphatemicby the authors, irrespective of the cutoff value.

Any kind of educational or counseling inter-vention related to diet was allowed in the interven-tional group. Passive and active comparators, suchas standard renal dietitian advice, were allowed.

Primary outcome was phosphorus level,whereas secondary outcome was Ca 3 P productlevel. End-study results were used for pooledanalysis.

Validity Assessment

Studies were evaluated according to the Jadadscale. No studies were excluded on the basis ofthe reported quality.

Data Abstraction

Studies that met the criteria outlined previouslywere assessed byone reviewauthor and checked byanother. Patients’ data, study size, population age,follow-up, interventions, and outcomes wereretrieved. Serum phosphorus and Ca3 P productlevels were converted to mg/dL and mg2/dL2,respectively (conversion ratios: 1 mmol/L 5 3.10mg/dL; 1 mmol2/L2 5 12.35 mg2/dL2). Dataentry into software was also double-checked. Alldisagreements were solved by consensus.

Quantitative Data Synthesis

The statistical analyses were performed usingthe RevMan software (version 5.0.23) developedby The Nordic Cochrane Center. Outcomeswere analyzed by the Mantel–Haenszel methodand themean difference (MD)was calculated. Re-sult uncertainty was expressed using 95% confi-dence intervals (CIs). The results estimates werebased on a fixed-effects model or random-effectsmodel in accordance with heterogeneity. Hetero-geneity was assessed using the I2 test. Heterogene-ity was assumed when I2 was .50%.Subgroup analysis was performed accordingly

in either dialysis or nondialysis state. Sensitivityanalysis was conducted in accordance with eitherfollow-up period ($4 months or ,4 months) orheterogeneity source.

Results

Search filters were applied in MEDLINE,CENTRAL, EMBASE, and mRCT and weobtained 48 citations in the different databases.Duplicated records were removed leaving a totalof 28 studies. From these, 17 studies were rejectedon the basis of abstract evaluation. From theremaining 11 studies, full-text assessment was per-formed for possible study eligibility. Four trialswere then excluded because they involved testingof phosphate-binding agents (2 studies), enteralnutrients, or education in patients without hyper-phosphatemia. Seven trials12–18 were included forqualitative and quantitative analysis. Two of themwere unpublished studies retrieved from mRCT(Fig. 1).14,18 Data from the study by Foley wereobtained after contacting the study coordinator.Table 1 shows the main characteristics of trials

and their conclusions. All trials were randomized.The study by Degen18 was the only one with

CALDEIRA ET AL286


adequate allocation concealment, whereas allother studies were unclear about this information.

Table 2 showsmethodological assessment of tri-als’ quality with Jadad score ranging from 1 to 3.

The 7 selected studies had 524 patients withhyperphosphatemia and CKD—6 studies assessed509 patients on dialysis and 1 study reported out-comes that evaluated 15 predialysis patients.Mean age of the patients was .50 years andfollow-up period ranged between 4 weeks and12 months. Methods used in the interventionswere variable, but they aimed to reduce phospho-rus levels through counseling or education in die-tary changes (Table 1).

The trial by Ashurst and Dobbie12 reportedmean serum phosphorus and Ca 3 P productlevels but did not report their standard deviations(SDs). For serum phosphorus level, mean SD ofboth intervention was calculated considering theP value to be .02 (authors reported a P value of,.02). For Ca3 P product level, because P valuewas nonsignificant, the worst known scenario wasconsidered. In the trial by Yokum et al.,15 SD wasused for educational intervention, whereas in thetrial by Morey et al.16 it was used for control.

These SD values were the highest among alltrials.19

End-study results were analyzed by random-effects methods because of the different nature ofeducational interventions.For the primary outcome, there was no hetero-

geneity in overall and subgroups pooled analysis.MD for phosphorus levels was 20.72 mg/dLand 95% CI ranged from 21.11 to 20.33 (P 5.0003). Although subgroup analysis showed thatthe intervention was effective for patients on dial-ysis with an MD of 20.75 mg/dL and 95%CI ranging from 21.23 to 20.28 (P 5 0.002), itdid not show statistical significance in patientsnot on dialysis who had an MD of 20.53 with95% CI ranging from 21.27 to 0.21 (P 5 .16)(Fig. 2).Sensitivity analysis of phosphorus level was con-

ducted in accordance with follow-up periods ofthe trials (Fig. 3). Trials with follow-up periodsof ,4 months did not show superiority of educa-tional intervention (MD: 20.38; 95% CI: 20.91to 0.15, P 5 .16), whereas those with longerfollow-up periods showed the benefits of a longereducational intervention with a weighted MD of

Figure 1. Flow chart ofstudies selection.

EDUCATION TO REDUCE SERUM PHOSPHORUS IN CKD 287


Table

1.Main

CharacteristicsoftheStudies

Study

Ashurstand

Dobbie,200312

Ford

etal.,

200413

Foley,200614

Yokum

etal.,

200815

Moreyetal.,

200816

Sullivanetal.,

200917

Degen,200918

Setting

Hemodialysis

Hemodialysis

Hemodialysis

Hemodialysis

Hemodialysis

Hemodialysis

Nonhemodialysis

Patients

Stable

hemodialysis

patients

with

hyperphosphatemia

Dialysis

patients

with

hyperphosphatemia

Hyperphosphatemic

ESRDondialysis

Stable

hyperphosphatemic

adultsundergoing

regularhemodialysis

Stable

adult

hemodialysis

patients

with

hyperphosphatemia

Hemodialysed

patients

with

hyperphosphatemia

Predialytic

hyperphosphatemic

patients

Numberof

patients

56

63

10

34

67

279

16

Hyperphosphatemia

criteria

Atleast1value

above1.7

mmol

(5.26mg/dL)of

serum

phosphate

inlast3months

Meanserum

phosphorusabove

6.0

mg/dLover3

months

Serum

phosphate

.5.5

mg/dLin

4of6laboratory

evaluationsover

6months

Atleast1Serum

phosphate

value

above.1.8

mmol/L

(5.57mg/dL)in

last

3months

Meanserum

phosphate

persistentlyabove

theUKRenal

Association

Standards

Committeetarget

,1.8

mmol/L,

(5.57mg/dL)

Recentserum

phosphoruslevel

andmeanserum

phosphoruslevelf

ortheprevious3

monthsgreater

than5.5

mg/dL

6-m

onthsmean

serum

phosphorus

.1.35mmol/L

(4.17mg/dL)

Age(years)

53(m

ean)

74%

above

50years

old

55(m

ean)

49(m

ean)

58(m

ean)

53(m

ean)

54(m

ean)

Follo

w-up

6months

6months

4weeks

4months

6/12months

3months

12weeks

Intervention

Educational

interventionand

one-to-onerenal

dietitianteaching

sessiongivenby

arenaldietitian

Monthly

additional

educational

sessionswith

educationaltools

suchasposters,

handouts,puzzles,

andan

individualized

phosphorus

trackingtool.

Weekly

nutritional

counseling

sessionsusing

amodified

versionof

motivational

interviewing

Pharm

acistandrenal

dietitianconsults

Monthly

dietetic

consultations

Educationon

avoidingfoods

withphosphorus

additiveswhen

purchasing

groceriesor

visitingfastfood

restaurants

Dietary

education

usingthe

PhosphorusPoint

System

Tool

Comparator

Norm

almanagement

onthedialysis

unit

withrenal

hemodialysis

dietitian.

Standard

dietitian

care

during

monthly

nutrition

rounds.

Traditionalmonthly

nutritional

counseling

Standard

care

with

renaldietitian

consultbutnot

pharm

acistconsult

Baselineandend-

study(6th

month)

renaldietitian

counseling

Standard

care

from

theirdietitiansand

nephrologists.

Dietitianprovidedlist

offoodshighin

phosphorusto

avoid,andlow

phosphorusfoods

toconsumemore

frequently

Outcomes

Serum

phosphate,

serum

calcium

andCa3

P

product

Before-and-after

knowledgetest

results,serum

calcium,

phosphorus,

parathyroid

horm

one,and

calcium/

phosphorus

productlevels.

Serum

phosphorus

levels

Changein

serum

phosphate

levels,

correctedcalcium,

Ca3

Pproduct

andiPTH

Serum

phosphate,

serum

calcium

andCa3

P

product

Phosphoruslevels,

foodknowledge

score,reads

ingredients

list

andreadsnutrition

facts

label

Serum

phosphorus

levels,dietary

intakeand

satisfactionand

knowledgeof

dietary

phosphorus

content

CALDEIRA ET AL288


21.07 and 95% CI ranging from21.49 to20.64(P , .00001).In 227 patients with hyperphosphatemia and

CKD (212 dialysis patients and 15 predialysispatients), Ca 3 P product level results were het-erogeneous with I2 5 58% for the dialysis sub-group. Education and/or counseling proved tobe superior to controls with an MD of 25.23mg2/dL2 (95% CI: 29.48 to 20.98, P 5 .02),but these results were not reproducible in the pre-defined subgroups. For patients on dialysis, MDwas 25.75 mg2/dL2, which was a statistically sig-nificant result with 95% CI ranging from 211.08to 20.42. The non-dialysis group did not havestatistically significant results with an MD of23.09 mg2/dL2 and 95% CI ranging from29.78 to 3.60 (Fig. 4).Sensitivity analysis of Ca 3 P product level in

accordance with follow-up periods of the trialscould not be conducted, although this outcomewas analyzed in accordance with heterogeneitysource (Fig. A1). Excluding the trial by Fordet al.13 helped remove heterogeneity, thus chang-ing the results in the overall and dialysis subgroups.Dialysis subgroup weighted MD was23.00 mg2/L2 with 95% CI ranging from 27.09 to 1.09.Overall mean reduction of Ca 3 P product levelwas 23.02 mg2/L2 (95% CI: 26.51 to 0.47),without any statistically significant differences.

Discussion

These results show that educational strategies inpatients with hyperphosphatemia and CKD canbe useful in the reduction of serum phosphoruslevels. This was well documented in the dialysisgroup, whereas education and/or counseling inpatients not on dialysis was not statistical signifi-cant in both outcomes. Reduced sample sizewith 15 patients underpowered comparison inthis latter subgroup.Analyzing trials with patients on dialysis, end-

study mean serum phosphorus Kidney DiseaseOutcomes Quality Initiative (K/DOQI) targetlevel of ,5.5 mg/dL20 was achieved in 50% ofthe analyzed studies, whereas none of the controlswere able to reach these values (5.7426.70 mg/dL). The pooled analysis showed that a decreaseof 0.75 mg/dL in phosphorus levels can beobtained in these patients when compared withthe controls.Sensitivity analysis suggested that maintaining

a long-term intervention may be important.

Conclusions

Educational

intervention

decreased

phosphate

levels

Extraeducational

sessionshowed

decreaseof

phosphorus

levels

Aggressive

counselingdid

notresultin

lower

serum

phosphoruslevels

withthis

patient

population.Larger

sample

sizeand/

orlongerfollo

w-

upcould

have

beenshownto

bebeneficial

Thephosphate

management

protocolwas

effective,andits

implementationwas

associatedwith

significantlybetter

serum

phosphate

control

Monthly

dietetic

consultations

improvedshort-

term

phosphate

levels

Educationof

patients

with

ESRDresultsin

modest

improvements

in

hyperphosphatemia

Analyze

dpopulation

wasvery

smallfor

definite

conclusions,but

educationdid

notreduce

significantlythe

phosphoruslevels

iPTH,intactparathyroid

horm

one;ESRD,end-stagerenald

isease

.



Pooled analysis of trials with longer follow-up ($4months) resulted in statistically significant de-creases of phosphorus levels, whereas short-termtrials did not achieve superiority of the interven-tion as compared with standard care.

KDIGO recommends that patients with CKDstages 3 to 5 should maintain serum phosphoruslevels in the normal range.21 K/DOQI recom-mendations target phosphorus levels of ,5.5mg/dL for both CKD stage 5 and dialysis patients.Stages 3 and 4 target phosphorus levels should be2.7 to 4.6 mg/dL.20 The trial by Degen initiallyenrolled 24 predialysis patients: 14 in CKD stage5, 8 in stage 4, and 1 in CKD stage 3.18 However,end-study results were only available for 15patients. Mean serum phosphorus levels in theintervention group were within the target values.Standard care did not meet stage 3 and 4 objec-tives, but because most of the patients were inCKD stage 5, results obtained can be consideredto be in the acceptable range of phosphorus levels.

Educational intervention showed superiority tocontrols in the reduction of the secondary out-come, that is, Ca3 P product level. After sensitiv-ity analysis, the tendency of pooled resultsremained in favor of the intervention, but withoutany statistically significant difference. For this pur-pose, the trial by Ford et al. was removed because itwas the main cause of heterogeneity in this out-come. This study had a very positive influence inthe meta-analysis, probably because of the superi-ority of the intervention group on food knowl-edge at baseline and after intervention.13

According to K/DOQI guidelines, Ca 3 Pproduct level should be maintained at ,55 mg2/dL2 in patients with CKD.20 Five studies evaluatedthis outcome, and mean Ca 3 P product levelfrom the interventions equivalent to that of theK/DOQI target Ca 3 P product level wasachieved in 4 trials. Only in 1 trial, standard caregroup was successful in reaching values of,55 mg2/L2.18 Educational strategies can be

Table 2. Quality Assessment of Studies

Trials Randomized

Randomization

Methods Double-blind

Blinding

Methods

Withdrawal and

Dropouts

Jadad

Score

Ashurst and Dobbie, 200312 X 21 (alternated) – – X 1

Ford et al., 200413 X X – – – 2

Foley, 200614 X X – – X 3Yokum et al., 200815 X X – – X 3

Morey et al., 200816 X X – – X 3

Sullivan et al., 200917 X X – – X 3

Degen, 200918 X X – – X 3

Figure 2. Forest plot evaluating end-study phosphorus levels. For interpretation of the references to color inthis figure legend, the reader is referred to the web version of this article.

CALDEIRA ET AL290


beneficial to achieve K/DOQI target Ca 3 Pproduct level.

Interfering factors, such as parathyroid hor-mone (PTH) levels and drug-use, were similar be-tween control and intervention groups in most ofthe studies. Only in the study by Sullivan et al.,was the PTH lower in the control group. Inter-group use of phosphate-binding drugs was similarwithin the studies that reported this informa-tion.13,14,16–18 Three studies reported the use of

vitamin D analogs. Two of them showed nodifferences between groups,16,17 whereas in thestudy by Ford et al., the use of vitamin D analogswas lower in the control group.13 Only 1 trialshowed baseline use of calcimimetics, but no dif-ferences were stated between intervention andstandard care groups.17

There is a close relationship between phospho-rus and protein intake.22 K/DOQI recommendsprotein intake of 0.6 to 0.75 g/kg/day for patients

Figure 3. Forest plot of sensitivity analysis of phosphorus levels in accordance with the follow-up periods ofthe trials. For interpretation of the references to color in this figure legend, the reader is referred to the webversion of this article.

Figure 4. Forest plot evaluating calcium–phosphorus product levels. For interpretation of the references tocolor in this figure legend, the reader is referred to the web version of this article.



with CKD stages 1 to 4.23 Protein restriction forthese patients can slow down disease progres-sion.24 Same guidelines recommendminimal dailyprotein intake of 1.2 g/kg/day for patients ondialysis to maintain good nutritional status becauselow protein intake can increase morbidity rate.25

Patients on dialysis often suffer from anorexia,and phosphorus-based food additives can be usedas flavor enhancers to help reach nutritional objec-tives,26 but they can also worsen phosphorus levels.Further, some studies showed that the recommen-ded amount of protein intake can lead to hyper-phosphatemia.27 In the selected trials, Morey et al.showed that educational strategy did not changenutritional parameters such as body mass index,albumin, handgrip strength, and mid-upper-armcircumference.16 In the study by Degen, serumcreatinine, albumin, weight, and body mass indexwere found to be similar between interventions.18

However, the follow-up periods in these studieswere short, preventing speculation of its resultsin long-term interventions, thus suggesting thateducational intervention may reduce serum phos-phorus without interfering with nutritional status.Some studies have showed that ingestion ofproteins with low phosphorus contents (lowphosphorus to protein ratio) could avoidmalnutri-tion and reduce mortality rate.28,29 Only 1 trialfrom the selected studies evaluated educationalintervention without a clear focus on protein–phosphorus restriction; Sullivan et al. successfullyused an intervention to avoid phosphorus-basedfood additives.17

Therefore, adequate balance should be individ-ually maintained on the basis of nutritional status,phosphorus, and calcium levels. Patients shouldnot consume processed foods, snacks, and softdrinks with large amounts of inorganic phospho-rus, and high phosphorus-to-protein ratio such asdairy products, sausages, or egg yolk. Counselingshould be conducted to reduce total phosphorusintake and to address preference of organic proteinswith low phosphorus-to-protein ratio to avoidmalnutrition. Relatively high phosphorus contentof vegetarian proteins is less absorbable because ofthe interference by phytates.29,30 Boiled food canalso reduce phosphorus content.31

Because only 45% of patients on hemodialysishave acceptable phosphorus levels according toDialysis Outcomes and Practice Patterns Study(DOPPS),32 additional therapeutic options suchas education or counseling are needed.

Psychoeducational interventionswere shown toimprove overall and postdialysis survival in 172predialysis patients versus 163 patients with pre-dialysis standard care, in a RCT with a meanfollow-up of 8.5 years.33 This result was also sup-ported by an observational study that analyzed 287predialysis patients assigned to multidisciplinaryeducation and 286 without this intervention.Mean follow-up was 11.7 months. Patients withmultidisciplinary education had lower mortalityand were less likely to initiate dialysis. Multidisci-plinary predialysis education was an independentprognostic factor for mortality rate in patientsnot on dialysis.34 Although the referred trialspointed out that education can be useful in pre-dialysis,33–35 RCTs are required to elucidatewhether education can improve phosphorusand Ca 3 P product levels in patients withhyperphosphatemia and CKD, irrespective ofwhether or not they are on dialysis.Independently of the methods used in educa-

tional and/or nutritional counseling actions, ourstudy showed that these nonpharmacologicalinterventions related to diet were effective in theimprovement of phosphorus levels in patientswith CKD and hyperphosphatemia. Educationmay also play an important role in reducing Ca 3P product level.

Implications to the Practice

These results are important for patients andhealthcare providers because beyond pharmaco-logical interventions, educational and/or counsel-ing interventions can be an additional resource toachieve desired phosphorus and/or Ca3 P prod-uct levels. For policy makers, this may be an effec-tive intervention to decrease high phosphorusburdens in CKD.Presented data support the fact that educational

interventions related to diet might be beneficial ifmaintained for a period of $4 months.

Implications to Research

Further studies using Ca3 P product level as anoutcome are required to possibly establish the ben-efit of the intervention in this outcome. The effectof education and/or counseling for patients onperitoneal dialysis is still unknown; therefore,more studies are needed to assess the efficacy ofthis intervention in peritoneal dialysis.

CALDEIRA ET AL292


Efficacy trials of these interventions with clini-cal outcomes, such as hyperphosphatemia-associatedmorbidities, are also essential to establisha definite role for educational strategies in thesepatients.

Assessment of mortality rate on educationand/or counseling evaluating patients withhyperphosphatemia and CKD is lacking, andgeneral CKD requires more powerful studiesthan those published for psychoeducationalinterventions.33,35

Limitations

Reduced number of trials with small number ofpatients and short-term follow-up periods werethe limitations for this study.

Overall, included studies had low quality (Jadadscore between 1 and 3), with a small number ofstudies reporting allocation concealment.

Studies by Foley and Yokum et al. could under-estimate effects of intervention because baselinephosphorus and Ca3 P product (in the latter trial)levels were lower in the control group and werenot statistically different.14,15

Patients not on dialysis were evaluated in only 1trial and its sample size was very small (n 5 15),thus making results in this subgroup inadequateto draft reliable conclusions.

Morey et al. enrolled 67 patients but phospho-rus levels of both intervention and control groupswere only supplied at the 12-month follow-up for48 patients.16 These were the results applied in thepooled analysis.

Conclusions

Educational interventions were effective inreducing phosphorus levels in patients with hyper-phosphatemia on dialysis. In comparison withcontrols, longer interventions ($4 months) wereefficient, whereas those with ,4 months follow-up were not. Education might play a role indecrease of Ca 3 P product levels.

AcknowledgmentsWe thank Dr. Sharon Foley for providing unpublished data.

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Figure A1. Forest plot of sensitivity analysis of calcium–phosphorus product levels.

Appendix

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