Endstager enalfailur eandr iskfactor sinPer u

Dr .AbdiasHur tado
HospitalAr zobispoLoayza

Endstager enalfailureandr iskfactor sinPer u. Theincreaseintheprevalenceof

chronic kidney disease(CKD) has been widely documented around the world.Peru
hasoneofthelowestprevalenceratesin LatinAmerica,duetotheeconomicsituation
of the country and the fact of having an unequal health system, in which onlythe
patients with health insurance have access to renal replacement therapy. The
alternatives,suchasincreasing thecoverageofsocialsecurityforall thepopulation or
rising the health expenses are not realistic at the present time. Currently there is
information in Peru aboutprevalence of the diseases with higher risk of developing
end stage renal failure, such as hypertension and diabetes. The implementation of a
kidney health program which prime objective is the screening of chronic kidney
disease isa goodalternative.Thecostbenefitanalysis,donewiththisinformation
on hypertensive patients older than 50 years, shows that this strategy could save
economicresourcesandisoflowercost.

Keywor ds:prevention,renaldisease,costs,

The increase in the prevalence of chronic kidney disease (CKD) has been widely
documentedindevelopedcountries(13)anditisexpectedthatinthefollowingyears
thisnumberwillincrease(45).InLatinAmericathereisasimilartendencybutwith
fewer numberof patientsonrenal replacement therapy (RRT) when compared with
developed countries (6, 7). The reason for this difference is that in Latin America,
many patientswhodevelopendstagerenalfailure(ESRF)donothaveaccesstoRRT
asthey havenomedicalinsurance,lackcoveragefromsocialsecurity,andhavealow
income such that they are unable to pay for RRT. This problem is clearly
demonstrated when we compare the prevalence of patients in RRT with the gross
domesticproduct(8).

CURRENTSITUATIONOFENDSTAGERENALDISEASEINPERU
TheprevalenceofpatientsondialysisinPeruwas166patientspermillion(ppm)in
2003, which is one of the lowest prevalence rates in Latin America (7). A major
reasonforthislowrateisthecountryseconomicsituation,asonly 4.4%ofthegross
domesticproductisinvestedinHealth.ThisfigurecontrastswithforLatinAmerica
in general(9). We also have to takeinto account that the Health Service in Peru is
unequaland fractured (10). InPeru,onlythosewith stable jobscarrysometypeof
medical insurance (private insurance, social security or army) and only these
individuals haveaccess to RRT programs. Theprevalenceof patientson dialysis in
Peruwhohaveoneofthesetypesofinsuranceisverysimilartodevelopedcountries
or to other countries in Latin America such as Uruguay or Puerto Rico, where the

accesstoRRTprogramsisuniversal(Table1).InPeru,themajority ofpeopledonot
havemedicalinsuranceandforthisreason,theyattendPublicHospitalswherethere
islimitedornoaccesstoRRTprogramsandconsequentlythesepatientsdiewithout
treatment.Public hospitals inPeruonlyprovidedialysiscoverageforpatientsunder
18yearsaspartoftheSeguroIntegraldeSalud(11).

CHARACTERISTICSOFTHEDIALYSISPOPULATION
TheaverageageofthepatientwithESRF inPeruis56.718 years57%aremen
and86%areonhemodialysiswithamonthlycostperpatientof$594.Theremaining
14%getambulatoryperitonealdialysiswithamonthlycostof $727.

In 40% of patients who begin RRT there is no etiological diagnosis for the ESRF.
Glomerulonephritis is the second most common diagnosis of ESRF, with a 20%
prevalence rate and is more common in patients under 50 years (Fig.1). This is
followed by diabetic nephropathy (16%) and hypertensive nephrosclerosis (11%).
Thesetwoaremorecommoninpatientsover60years.

There is an annual increase in the incidence of patients with ESRF of uncertain

diagnosis, diabetic nephropathy and nephrosclerosis of 20%, 12% and 22%,
respectively. In contrast, the incidence of glomerulonephritis is decreasing (9%).
(Fig. 2). This is consistent with the worldwide trend of a dramatic increase in
diabetes, obesity/metabolic syndrome, and hypertension in both developing and
developedcountries.

CHARACTERISTICSOFDISEASESWITH CHRONICRENALDISEASE
RISK INPERU
Hypertension: In 2004, a study performed on 14,256 patients older than 18 years
among26citiesshowedthat23.7%hadhypertension. Ofthesepatients,55%didnot
knowabouttheirdiagnosisandonly14.7%hadadequatetreatment.Theprevalenceof
hypercholesterolemia was 10% (12). This frequency of hypertension is less than
observedindevelopedcountriessuchastheUnitedStateswheretheprevalencerateis
currently31%,butisconsistentwiththerisingfrequencyofthisconditionthroughout
theworld.
Diabetesmellitus: In 1999 astudy in Peru reported that the prevalence ofdiabetes
mellitus was 7.6% in urban areas witha lower prevalence in rural areas and inthe
populationlivingathighaltitude.Othercardiovascularriskfactorsfoundinthisstudy
were: obesity (22.8%), tobacco use (16.5%), alcohol consumption (23.6%) and
sedentary lifestyle(66%)(13).
Primary Glomer ulonephr itis: In Peru glomerulonephritis is the second most
common

cause

of

ESRF.

Focal

segmental

glomerulosclerosis

and

membranoproliferative glomerulonephritisarethemostcommondiagnoses inadults

(14).Therateof newcasesofglomerulonephritis diagnosedbyrenalbiopsyis14.5
ppm.
Children with low birth weight have an increased risk of developing cardiovascular
disease,diabetes,hypertensionandrenaldisease(15).InPeruapproximately 14%of
allbirthshavealowbirthweight(9).

CHALLENGESOFRENALDISEASEINPERU

Onealternativetosolvetheproblemofthenumberofpatientswhodonothaveaccess
toRRTwouldbetoincorporatethemajorityofthepopulationintothesocialsecurity
system(16). Thisisunrealisticintheshorttermandwouldalsoresultinanincrease
incostthatthecurrentsocialsecuritysystemcouldnotsustain.Currentlytheannual
investmentinhealthisaround601milliondollarstheinvestmentinRRTrepresents
6%of this budget. If Peru were to provide a similar coverage as the average Latin
American country that provides RRT to a mean of 380 individuals per million
population, the total health care costs for providing this service would increase to
12.8%. This proposal would cause some conflict with the Health Board as their
prioritiesarefocused onmoreprevalentdiseasessuchasinfectiousdiseasesandother
conditionssuchaschronicmalnutrition inchildrenandinfantmortality (10).
The current viewpoint is that the best way to attack the rising frequency of kidney
diseaseinPeruistofocusattentiononprevention. PreventingtheriseinESRFwill
bothbenefitthepatientssufferingfromtheseconditionsandalsolimitthehealthcare
costswhicharescarceandunlikelytoincreaseintheshortterm.

BenefitCostAnalysisofaPr ogramforthePreventionofChronicKidney
DiseaseinHyper tensivepatientsinPer u
ThescreeningforconditionsconsideredasriskfactorsforCKD,isaninternationally
recommended strategy (17, 18) and has the purpose to develop and implement
preventionapproachestodelaytheprogressionofCKDandtodecreasetheburdenin
health careexpenditure.
Abenefit cost analysis for the prevention ofthe progression of CKD was done in
hypertensiveadultsover50years.Thepurposewastodeterminewhetherascreening
programinvestigating the presenceofproteinuria with initiation oftreatment would

be favorable. Adecisionanalysis was made to comparestrategies: annual screening

vs.noscreening,followedbytreatmentwithenalaprilinthosewithproteinuria.The
NHANESIIIstagesofCKDwereusedindefiningthismodel (19).

Thescreeningprogramconsistedofoneannualvisittothegeneralpractitioner,who
checked for proteinuria with a urine dipstick test on three consecutive days and
measuredserumcreatinine(tocalculatetheglomerularfiltrationrateandthestageof
CKD).Thepatientswithpersistentproteinuria(definedastwopositiveresults)hada
24 hour urine collection performed for proteinuria. The patients with CRF stage 1
were followed and treated with enalapril by their general practitioner. The patients
with stages 24 were referred to a nephrologist. The appointments timing was as
follows:atbooking,day7and15,6months,andthereaftereveryyearupto5years.
Serum creatinine was measured once a year as well as urine dipstick looking for
transitionofCKDfromonestagetothenextone.
The no screening strategy consisted in the diagnosis and treatment of hypertension.
CKD was diagnosed at the annual evaluation as an incidental finding based on
symptoms.
ThepotentialbenefitsofscreeningincludedthereductionoftheprogressionofCKD
tomoreadvancedstageswhichwouldrequiretreatmentwithEnalapril(2022).The
estimatedreductioninprogressionwasprojectedtobe30%(23).

The costs of annual screening included: urine dipstick, 24 hour urine proteinuria,
serum creatinine, medical consult (general practitioner and nephrologist) and the
treatmentwithenalapril.Treatmentforstages2,3,and4suchascalcium,vitamins,
iron and erythropoeitin were also included as well as other drugs to improve blood
pressurecontrol,andthecostsofRRT(hemodialysisandotherdrugs).

DataAnalysis: Thevariationsintheprobabilityofeventsandinthecostsofdiagnosis
and treatment process were evaluated with an sensitivity analysis, and for this, the
time span for the evaluation of events was considered as 1 year or more for
progressiontostages24,andfiveyearsforprogressiontoESRF.SoftwareDATA
TreeforHealth Careversion 3.5wasused(24).
ThemainoutcomemeasurewastheamountofAmericandollarsthatweresavedat
the end of the 5 year period of annual screening with treatment with enalapril in
patientsolderthan50years.Thiswascomparedwiththenointerventiongroup.The
secondary outcome measure was the amount of American dollars saved per patient
peryear.
Results: Considering an initial population of 1667,733 hypertensive patients older
than50years,whichrepresent50%ofhypertensivepopulation inPeru,andassuming
a sensitivity to detectproteinuria withthe urine dipstick that varies between 75 and
90%(23,25),thestatisticalprobabilityforCKDprogressionforpatientswithnormal
or diminished renal function are shown in Fig. 3. The results in the group of
evaluatedhypertensivepatientsareshownintable2.
The study shows that the proposed screening intervention program using a simple
urine dipstick followed by treatment for persistent proteinuria with enalapril in
hypertensive subjects older than 50 years is cost beneficial with an average total
saving,ifESRFstageisavoided,of$188,518,645overfiveyearsandof$19.70per
patient peryear.
CONCLUSIONS
TheprevalenceofpatientsondialysisinPeruisoneofthelowestinLatinAmerica.A
majorreasonforthislowrateisthecountryseconomicsituation andtheexistenceof
anunequalhealthsystem,whichonlyallowsaccesstoRRTprogramstopatientswith

medical insurance. The alternative would be to incorporate the majority of the

population into the social security system this is unrealistic in the short term and
wouldalsoresultinacost increasethatthecurrent social security systemcouldnot
sustain.Presentlywe have informationaboutprevalenceofthediseaseswithriskto
developESRF,suchashypertension,diabetesandglomerulonefritis,forthisreason it
isviabletoproposearenalhealthprogramthatwillhaveasprimeobjectivetheCKD
screeninginthosepathologies.Thecostbenefitanalysis,donewiththisinformation
on hypertensive patients older than 50 years, shows that this strategy could save
economicresourcesanditisoflowercost.

ACKNOWLEDGMENTS
WethankDr.EdmundoAlvafromCentrodeHemodialisis,SeguroSocialdeSalud,
Dr.AugustoSaavedrafromThePeruvianSocietyofNephrology.

REFERENCES

1. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic

kidney disease and decreased kidneyfunction in the adult US population:Third
National Health and Nutrition Examination Survey. Am J Kidney Dis 41:112,
2003
2. AtkinsRC:Theepidemiologyofchronickidney disease.KidneyInt67(Suppl94):
S14S18,2005
3. El Nahas AM, Bello AK: Chronic kidney disease: the global challenge. Lancet
365:33140,2005
4. XueJL,MaJZ,LouisTA,CollinsAJ:Forecastofthenumberofpatientswithend
stage renal disease in the United States to the year 2010. J Am Soc Nephrol
12:27532758,2001
5. LysaghtMJ:Maintenancedialysispopulationdynamics: Currenttrendsandlong
termimplications.JAmSocNephrol13:S3740,2002
6. Mazzucchi N, Schwedt E, Fernandez JM, et al: Incidencia y Prevalencia del
tratamiento de la insuficiencia renal extrema en Latinoamrica. Nefrologa
Latinoamericana9:191195,2002
7. CusumanoA,DiGioiaC,HermindaO,LavoratoC:TheLatinAmericanDialysis
and Renal Transplantation Registry Annual Report 2002. Kidney Int 68 (Suppl
97):S46S52,2005

8. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: Global overview of

patients, treatment modalities and development trends. Nephrol Dial Transplant
17:20712076,2002
9. RodriguezIturbeB,BellorinFontE:Endstagerenaldiseasepreventionstrategies
inLatinAmerica.KidneyInt68(Suppl98)S30S6,2005
10. Lineamientos de Poltica Sectorial para el Perodo 2002 2012 y Principios
Fundamentales para el Plan Estratgico Sectorial del Quinquenio Agosto 2001
Julio2006,Availableat:www.minsa.gob.pe/portal/Lineamientos/ lineamientos7
.pdf
11. SeguroIntegraldeSalud,Availableon:http://www.sis.minsa.gob.pe/
12. Sociedad Peruana de Cardiologa. Available at: http://www.gestion.com.pe/GM/
archivo/2005/may/22/2actu.htm
13. Seclen S Leey J Villena A et al: Prevalencia de Obesidad, Diabetes Mellitus,
HipertensinArterialeHipocolesterolemiacomoFactoresdeRiesgoCoronarioy
Cerebrovascular enPoblacin Adulta de la Costa, Sierra y Selva del Per. Acta
Med.Peru17:812, 1999.
14. HurtadoA,AsatoC,EscuderoEetal:Distinctpatternsofglomerulardiseasein
Lima,Per. ClinicalNephrology,200053:325332
15. Luyckx V, Brenner B: Lowbirth weight, nephron number, and kidney disease.
KidneyInt68(Suppl97):S68S77,2005
16. Petrera M: Factibilidad Econmica de la EPSS Aplicacin al caso peruano
OPS/OMSPer.Availableat:http://www.paho.org/Spanish/DPM/SHD/HP/hpxi
taller04prespetrera.pdf
17. Li PK, Weening JJ, Dirks JH et al: A report with consensus statements of the
InternationalSocietyofNephrology2004ConsensusWorkshoponPreventionof

10

ProgressionofRenalDisease,HongKong,June29,2004.KidneyInt67(Suppl.
94):S2S7,2005
18. Dirks JH, De Zeeuw D, Agarwal SK et al: Prevention of chronic kidney and
vascular disease: toward global health equitythe Bellagio 2004 Declaration.
KidneyInt68(Suppl98):S1S6, 2005
19. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,
classification,andstratification.AmJKidneyDis39(Suppl1):S1S266, 2002
20. Ihle BU, Whitworth JA, Shahinfar S, ET AL: Angiotensinconverting enzyme
inhibitioninnondiabeticprogressiverenalinsufficiency:acontrolleddoubleblind
trial.AmJKidneyDis27:48995, 1996
21. Jafar TH, Stark PC, Schmid et al:Proteinuria as a modifiable risk factor for the
progressionofnondiabeticrenaldisease.KidneyInt60: 113140, 2001
22. JafarTH,StarkPC,Schmidetal:Progressionofchronickidneydisease:therole
of blood pressure control, proteinuria, and angiotensinconverting enzyme
inhibition:apatientlevelmetaanalysis.AnnInternMed139:244252. 2003
23. Boulware LE, Jaar BG, TarverCarr ME et al: Screening for proteinuria in US
adults:acosteffectivenessanalysis.JAMA290: 31013114, 2003
24. DATA3.5User`sManual.Copyright1999byTreeAgeSoftware,Inc.
25. Gansevoort RT, Verhave JC, Hillege H et al:The validity of screening based on
spot morning urine samples to detect subjects with microalbuminuria in the
generalpopulation.KidneyIntSuppl.2005Apr(94):S2835.

11

Table1. DistributionofthePeruvianpopulationaccordingtothedifferenthealth
servicesavailableinthecountry.2003

Health Services

ARMY

Population

Patients
in
dialysis

Patients in
dialysisper
million
population

780,000

153

196

PRIVATE

2,500,000

9.6

16

SOCIAL
SECURITY

5,200,000

20

4102

789

HEALTH
MINISTERY

17,520,000

67.4

85

TOTAL

26000,000

100

4328

168

12

Table 2. Cost benefit analysis for the prevention of the progression of CKD in
hypertensiveadultsover50years

EvaluatedG roup:
Hypertensivepatientsolderthan50years
Hypertensivepatientsolderthan50years

Aver ageSavingsinUSDollar s
(Scr eeningvs.NotScr eening)

Forthetotalofhypertensivepatientsin5years

$66501,742.00

Forthetotalofhypertensivepatientsperyear

$13300,348.40

Foreachhypertensivepatientspatientin5years

$58.57

Foreachhypertensivepatientsperyear

$11.70

13

Fig.1. Common causesof EndStageRenalFailureamong

patientsondialysisaccordingtoage.2003

Uncertain Glomerulonephritis Diabetes Nephrosclerosis

100%
90%
80%
70%
60%

% 50%
40%
30%
20%
10%
0%

15203040
1
2
3
4

506070>80
5
6
7
8
AGE

14

Fig. 2.CommoncausesofEndStageRenalFailureamongpatients
ondialysiswithin20002002.

2000 2001 2002

2000
1800

20%

1600

numberofpatients

1400
1200

9%

1000

12%

800

22%

600
400
200
0
uncertain

Glomerulonephritis

Diabetes

CauseofEndStage RenalFailure

15

Nephrosclerosis

Fig3. Decisiontreein proteinuriascreeningin patientswithhypertension

Treatmentwith
Enalapril
Enalapril

CKD1
p1

CKD1

CKD24

pCKD1

p2

ESRD

Proteinu ria

p3

pA

CKD24
CKD24
pCKD2_4

p4

ESRD
p5

Screeni ng

NRF
p6

NRF

DRF

pNRF

p7

ESRD

NotProteinuria

p8

pB

DRF
DRF
pDRF

p9

ESRD
p10

HBPinpeople
>50yearsold

CKD1
p11

CKD1

CKD24

pCKD1

p12

ESRD

Proteinu ria

p13

pC

CKD24
CKD24
pCKD2_4

p14

ESRD
p15

Not
Screeni nig

NRF
p16

NRF

DRF

pNRF

p17

ESRD

NotProteinuria

p18

pD

DRF
DRF
pDRF

p19

ESRD
p20

HBP
=
CKD1 =
CKD24 =
NRF
=
DRF
=
ESRD =
pA
=
pB
=
pC
=
pD
=
pCKD1 =
pCKD24 =
pNRF
=
pDRF
=
p1top20 =
1to20 =

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20

HighBloodPressure
ChronicKidneyDiseasewithGFR>90ml/minute.
ChronicKidneyDiseasewithGFRbetween14and89ml/minute.
NormalRenalFunction(GFR 60ml/minute).
DecreasedRenalFunction(GFR<60ml/minute).
EndStageRenalDisease(Stage5byKDOQI)
Probabilityofproteinuriabydipstickandtheninorineof24hours.
ProbabilityofHBPwithoutproteinuriabydipstick.
PrevalenceofproteinuriainHBPinseveralreportedstudies(NHANESIII).
1pC
ProbabilityofpeoplewithHBPandproteinuriatobeinStage1.
1pCKD1
ProbabilityofpeoplewithHBPwithoutproteinuriatohaveGFR 60ml/minute.
ProbabilityofpeoplewithHBPwithoutproteinuriatohaveGFRbetween15and60ml/minute
(1pNRF).
Probabilitiestomakeprogressornottomoreadvancedstages.
ValuesinAmericandollarsofBenefitCostindifferentoutcomes:(CostofRRTCostof
screeningprogramorregularcontrol)*numberofpatients.

16

17