Early chronic kidney disease diagnosis, management and models of care 2015.docx

8/18/2019 Early chronic kidney disease diagnosis, management and models of care 2015.docx

1/17

Correspondence to:

D.J.O.

LSE Health,

Cowdray House,London School ofEconomics andPolitical Science,Houghton Street,

London WC2A 2AE,

UK O! J!W!,P!G!K !"!

#e$artment of%enal

&edicine, Salford%oyal 'HS

(oundation )rust, Stott Lane,

Salford &* +H#,UKD! J!O!, J!R!"!'ational nstituteof #ia-etes and#igesti.e and

Kidney #iseases,'ational nstitutesof Health,/ethesda, 01

Center #ri.e,/ethesda, 2+32425*,USA A!S!N!"!

donal!o6donoghue7 srft!nhs!u8

Introductio

nChronic kidney

disease (CKD)

is a condition

characterized by

kidney damage

and/or

dysfunction, as

well as an

increased risk of

cardiovascular disease.,! "y#e ! diabetes mellitus

("!D$) and hy#ertension cause u# to twothirds of

CKD%& less fre'uent causative factors include

glomerulone#hritis, ne#hrolithiasis and #olycystic

kidney disease., CKD is currently classified by

measuring the estimated glomerular filtration rate

(e*+) and urinary albumin e-cretion rate ("able ).atients with an e*+ 01 ml/min/.2& m! are

assessed for ty#ical markers of renal damage, such as

abnormalities in urinary sediment or organ structure,

to hel# confirm a diagnosis of CKD.0 3n a small

#ro#ortion of cases, #rogressive CKD leads to end4

stage renal disease (56D), where dialysis and/or

kidney trans#lantation is essential for survival. "he

rate of CKD #rogression varies between #atients,

de#ending on the aetiology and #athology of the

disease.2,7

CKD is #revalent in most high4income countries.,2

"he #revalence rate of CKD among non4

institutionalized adults in the 869 increased from!.1: (;: C3, 1.of &.2: (;: C3, !.

). =y contrast, the #revalence of stages &Competing interests

)he authors declare no com$eting interests!

atients with 56D re#resent >1.: of the total

#o#ulation in many high4income countries, but

account for

5stimates suggest that ?86@ trillion is s#ent on

56D care worldwide.! "he clinical and economic

rationale for designing timely and a##ro#riate health4

system res#onses to limit #rogression of CKD to56D, therefore, is clear.&

Olivier J. Wouters, Donal J. O’Donoghue, James Ritchie, Panos G. Kanavos and Andrew S. arva

A%stract : Chronic 8idney disease CK#" is $re.alent in many countries, and the costs associated with the care

of $atients with end4stage renal disease ES%#" are estimated to e;ceed US therefore, additional research is re?uired to increase awareness of the ris8 factors

for CK# $rogression! Systems modelling can -e used to e.aluate the im$act of di=erent care models on CK#

B9"85 5G35A6 H NEP&RO'OG( GI8$5 H 98*86" !1 H )


2/17

RE*IEWSoutcomes and costs! )he US ndian Health Ser.ice has demonstrated that an integrated, system4wide

a$$roach can $roduce nota-le -enets on cardio.ascular and renal health outcomes! Economic and clinical

im$ro.ements might, therefore, -e $ossi-le if CK# is reconce$tualiBed as a $art of $rimary care! )his %e.iew

discusses which early CK# inter.entions are a$$ro$riate, the o$timum time to $ro.ide clinical care, and the

most suita-le model of care to ado$t!

Wouters, ! D! et al. at. Rev. e!hrol. )), 31F52 215"> $u-lished online 3 Dune 215> doiG1!10+nrne$h!215!+5

Ke! points

J Chronic 8idney disease CK#" is associated with early4onset

cardio.ascular disease, end4stage renal disease and $remature

death

J Patients with mild4to4moderate reductions in estimated

glomerular ltration rates often ha.e comor-idities that are more

rele.ant to their current and future well4-eing than a CK#

diagnosis

J An integrated care $athway is re?uired for $atients with CK#

J A growing num-er of e;$eriences from di=erent countries ha.e

shown that $rimary care models can lead to im$ro.ements in

cardio.ascular and renal health outcomes among CK# $atients

J &ore research into early identication, screening, monitoring and

management strategies for CK# is re?uired> this research should

include the esta-lishment of CK# registries to $ermit healthF

economic analyses

+a%e ) : #enition and classication of CK#

Categor!easure Description

GFR (ml/min/1.73 m2 )

'ormal or high

&ildly decreased

&ildly to moderatelydecreased

&oderately to se.erely decreased

Se.erely decreased

Kidney failure

Albuminuria (mg/g per 24 h)

A1 'ormal to mildly increased

A2 &oderately increasedA0 Se.erely increased

CK# is dened as either 8idney damage or I(% J* mlmin1!0m2 for #ata o-tained from Kidne" #nt. Su!!l. -, 5F1 210"!

countries (+igure !).;,7

the lifetime risk of develo#ing CKD stages *&a

(e*+ >01 ml/ min/.2& mL), *&b (e*+ >

ml/min/.2& mL), * (e*+ >&1 ml/min/.2& mL),

and 56D for an individual born in the 869 in this

generation is ;.:, &&.0:,.:, and &.0:,

res#ectively.! "hese estimates

vary markedly by gender and

ethnicity.

revalence rates for CKD are

based on e*+Ma #ro-y

measure of renal functionM

which is usually calculated

using the CKD 5#idemiology

Collaboration (CKD< 53) or

$odification of Diet in enal

Disease ($DD) study

formulae (+igure &). 8rinarylevels of albumin uria #rovide

su##lemental information on

the severity of CKD ("able ).

3n addition to these two

measures, other diagnostic

#rocedures (for e-am#le, renal

tract imaging) are #erformed in

the maNority of #atients with

newly diagnosed CKD,!

although some guidelines

advocate a more rationed

a##roach.!0 9 retros#ective

cohort study of ,72 #atientswith CKD managed at

$assachusetts *eneral

Oos#ital in =oston, 869,

found that clinicians fre'uently

ordered renal ultrasonogra#hy

and other biochemical tests (for

e-am#le, serum #rotein

electro#hor eses and

#arathyroid hormone

measurements) during the

initial evaluation of CKD.

"hese test results, however,

only affected the original

diagnosis (based on e*+ andurinary albumin e-cretion rate)

and/or the clinical care in >:

of cases.! "his finding im#lies

that many of the diagnostic

tests conducted during the

initial evaluation of #atients

with CKD are redundant, and

su##orts the economic

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RE*IEWSargument for distinguishing between the diagnosis

of early4stage CKD and the assessment of

com#lications in #atients with CKD stages and .

Age2associated decine in rena function "he estimatedhigh lifetime risk of CKD calls into 'uestion a distinction between early4

stage CKD and normal age4associated decline in renal function. 9reduction in renal blood flow and renal mass, as well as #rogressive

glomerulosclerosis, are #art of the normal ageing #rocess, with e*+

ty#ically falling by P1.2 ml/min/.2& m ! #er year from the age of 1

years.!2 "his rate of #rogression seems nonlinear, with e*+ loss slowing

below ml/ min/.2& m! among elderly #atients.!7 o#ulation studies

have found that the maNority of #atients with CKD are aged ?01 years,

and that most of these #atients do not e-hibit marked albuminuria. !;,&1

Difficulties are, therefore, a##arent in differentiating between age4

associated loss of kidney function and renal disease. & 5lderly #atients

with a given reduction in e*+ are less likely to #rogress to 56D than

are non4elderly #atients with an e'uivalent reduction in e*+. !7,&! "he

role of the ageing #rocess has long been recognized in other organ

systems% for e-am#le, the natural decline in forced e-#iratory volume

with age indicates #remature or accelerated loss of res#iratory function.&&

$eta4analyses of ?. million #atients have identified that the risk of

56D is almost e'uivalent between #atients aged above or below 0

years of age with an e*+ .& mg/mmol.&,& 9lthough the interaction between

renal function and #roteinuria does seem to differ with ageM#otentially

due to the com#eting risk of deathMthese data have been inter#reted as

evidence against the introduction of differing thresholds for defining

CKD based on age. +urthermore, it has been argued that senescent

changes in e*+ are caused by other disease #rocesses, such as

hy#ertension and diabetes mellitus, rather than a natural decline in renal

function.&0,&2 "he differing inter#retations of these data on e*+ loss in

the elderly underscore the need to consider e*+ trends as a #art of the

clinical assessment. Ahether these changes in e*+ reflect intrinsic renaldisease or normal ageing is unclear, but CKD and senility are associated

with an elevated risk of morbidity and mortality in an additive fashion.&

$any #atients with CKD e-hibit comorbidities. 3n the 8K, P0: of

#atients aged ?0 years with CKD e-hibit at least four additional

morbidities, including #rostate, res#iratory, and cardiac diseases in men,

and bone, Noint, and mental health #roblems in women. &7 9lthough it is

acknowledged that multi4morbidity im#oses an increased need for health

care, the risk factors for multi4morbidity are #oorly defined. &;,1 +urther

work is re'uired to determine whether renal im#airment in elderly

#atients is either associated with or causative of other conditions.

B9"85 5G35A6 H NEP&RO'OG( GI8$5 H 98*86" !1 H -

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1988–1994

1999–2004

2007–2012

RE*IEWS3igure ) : Pre.alence of CK# -y stage in the

USA -etween 13++ and 212! )he $re.alence

estimates are -ased on sam$les of

non4institutionaliBed adults aged 2 years"

who $artici$ated in the 'ational Health and

'utrition E;amination

Sur.ey 'HA'ES" during the study years

indicated! )he sam$le siBes .aried across 13++F133 n M 15,++", 1333F2 n M 10,200",

and 2F212 n M 15,52"! )he $roteinuria

measures were -ased on al-uminGcreatinine

ratios from s$ot morning urine sam$les! )he

estimated glomerular ltration rates were

calculated using the CK#FEP creatinine formula!

Stage 0 CK# corres$onds to a glomerular

ltration rate of 0F53 mlmin1!0 m2! )he error

-ars show the 35N condence inter.als! #ata

were o-tained from the US%#S 21 Annual

#ata %e$ort!3 )he data re$orted here were

su$$lied -y the US%#S! )he inter$retation and

re$orting of these data are the res$onsi-ility of

the authors and in no way should -e seen as anoOcial $olicy or inter$retation of the US

go.ernment! A--re.iationsG CK#, chronic 8idney

disease> US%#S, United States %enal #ata

System!

E4uations to estimategomeruar 5trationrate "he creatinine4basedformulae used to estimate

glomerular filtration rate

(*+) have other known

limitations, in addition to the

confounds of age4associateddecline in renal function

described above.,! "hese

formulae were originally

develo#ed to identify #atients

with an e*+ Q01 ml/min/.2&

m! at risk of renal failure, and

are not sensitive for

identification of CKD stages

or ! (+igure &).& 3n isolation,

e*+ is of little value for

earlystage CKD intervention

efforts. 6ome clinicians have

called for the removal of thefirst two stages of CKD from

the KDE3 guidelines,

whereas others have #ro#osed

alternative methods to classify

the early stages of CKD. "he

$DD study e'uation tends to

underestimate the true *+

among individuals with normal

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5/17

Stage 1 Stage 2 Stage 3 Stage 4 Stage 5

CKD stage

Percentage o t!e pop"#at$on

0

%.00

5.004.00

3.00

2.00

1.00

7.00

RE*IEWSkidney function,0&mg/ mmol.0,!0 "his strategy might lead to future cost savings by

reducing health4care use among #atients who are wrongly diagnosed with

CKD. 9n international standard reference for cystatin C measurement has

now been agreed u#on (5$4D92/3+CC),; but the assay is not yet

widely available. Diagnostic accuracy might im#rove if u#take of the

assay increases.

A%uminuria

9lthough urinary albumin e-cretion rates #rovide valuable diagnostic

data, tests for albuminuria have limitations, such as #oor test


6/17

RE*IEWSltration rate, e;ce$t for the US study data, which used the CK#FEP

creatinine formula! )he Chinese,1+ Korean,21 S$anish,22 and US3

studies measured $roteinuria using the s$ot morning urinary

al-uminGcreatinine ratio! )he remaining studies used a urine

di$stic8 analysis for $roteinuria! )he Chinese study1+ also measured

haematuria -y di$stic8 test!

therefore, neither clinically a##ro#riate nor, given

the global scale of the disease, economically

feasible. Clinical care might im#rove if early4stage

CKD with risk of #rogression to 56D is

differentiated from early4stage CKD that is unlikely

to advance (=o- ). 3nterventional studies might

also benefit from a selective definition of early4

stage CKD. +or e-am#le, the benefits of dietary

salt restriction have not been conclusively

established.2! 9 post hoc analysis of the

B"9*5" and "9B6C5BD studies identified

no renal benefit of dietary salt restriction among

#atients with early CKD.2& *iven the re#orted benefits of a low salt diet for #atients with

advanced renal failure,2 it is #ossible that certain

#atients might be better suited than others to

dietary salt restrictions.

+"e screening de%ate

9 systematic review of screening, monitoring and

treating #atients with CKD stages


7/17Stage 1 Stage 2 Stage 3 Stage 4

CKD–&P' creat$n$ne

(D)D st"d*

Stage 5

CKD stage

0

5.00

%.00

7.00

8.00

4.00

3.00

2.00

1.00

9.00

RE*IEWS3igure - : Com$arison of CK# $re.alence as

determined using di=erent formulae to estimate

glomerular ltration rate CK#FEP creatinine

.ersus the four4.aria-le %# study" in the USA

-etween 1333 and 2! )he $re.alence

estimates are -ased on sam$les of

non4institutionaliBed adults aged 2 years"

who $artici$ated in the 'ational Health and'utrition E;amination Sur.ey 'HA'ES" during

these years n M 10,200"! )he CK#FEP data

re$orted here were su$$lied -y the US%#S!3 )he

inter$retation and re$orting of these data are

the res$onsi-ility of the authors and in no way

should -e seen as an oOcial $olicy or

inter$retation of the US go.ernment! )he

four4.aria-le %# study data were re$orted -y

Coresh et al!23 /oth studies used measures of

al-uminGcreatinine ratios from s$ot morning

urine sam$les! Stage 0 CK# corres$onds to a

glomerular ltration rate of 0F53 ml min1!0

m2! )he error -ars show the 35N condence

inter.als! )he $re.alence of stage 5 CK# was not

estimated with the %# e?uation in this

study23 as it was deemed that Qestimates of this

stage are li8ely to -e unrelia-le due to the small

num-er of indi.iduals and the li8elihood that

many of these indi.iduals are ill or recei.ing

dialysis and would ha.e a low res$onse rate!R23

A--re.iationsG CK#, chronic 8idney disease>

US%#S, United States %enal #ata System!

"he rate of increase in the

incidence of 56D is slowing

in some countries, including

9ustralia, Canada, northern5uro#ean countries, Bew

Uealand and the 869, although

these trends vary by subgrou#s,

such as age and race.1 "he

stabilization of these incidence

rates might reflect

im#rovements in

cardiovascular risk

management in the general

#o#ulation and among

individuals with "!D$ and/or

hy#ertension, although this

effect has yet to be shownconclusively.

E9idence gaps

"he conflicting views of the

9C, 96B, B3C5 and 866"+

highlight the need for more

C"s to evaluate

identification, screening,

B9"85 5G35A6 H NEP&RO'OG( GI8$5 H 98*86" !1 H :



8/17

Percentage o t!e pop"#at$on

RE*IEWSmonitoring and treatment of early CKD. 3n the

meantime, #o#ulation health management could

focus on the control of vascular risk factors and on

the #atients with CKD who are likely to #rogress to

56D, and will subse'uently #lace a burden on

healthcare costs.1!,1& *iven the asym#tomatic and

insidious onset of CKD, research into new biomarkers and #rognostic techni'ues is

essential.11 ml/min/.2& m!, but the risk of death was

increased at e*+s >;1 ml/min/.2& m !. 9lthough these data could be

inter#reted to su##ort defining a mild reduction in renal function as #art

of a disease state, it is im#ortant to consider the difference in the

threshold for the risk of death and 56D. "hese findings also raise the

'uestion of #o#ulation risk versus individual risk. atients with early

CKD but at low risk of 56D still carry an elevated risk of other

com#lications com#ared to the general #o#ulation. 6creening #atients

for reductions in e*+ might not contribute meaningful #rognosticinformation at an individual level with regard to 56D risk. 6mall

reductions in e*+, however, can im#rove discrimination in models of

cardiovascular risk, and the rate of change in e*+ might be a more

effective #redictor of risk, as com#ared to absolute values.,0

6tage

cardiovascular risk rather than renal risk. "his assessment might be

#articularly relevant when considering elderly #atients with reduced

measures of e*+ but no a##reciable albuminuria. "he risk of 56D and

death was associated with increased albuminuria in a linear manner in the

two meta4analyses described above,!,& further em#hasizing the

im#ortance of albuminuria in defining the risk of CKD #rogression.

odes of CKD care+"e Wagner c"ronic care mode

6ome evidence suggests that the #revailing care strategy for CKD should

com#rise three #hases (+igure ). rimary care management of vascular

disease risk during early4stage CKD forms the first #hase of the care

strategy, which could involve e-ercise, dietary changes, smoking

cessation, blood #ressure control, glycaemic and li#id control and

#eriodic monitoring of kidney health. "he second #hase could #rovide

structured care to target comorbidities, such as anaemia, bone disease and

secondary hy#er#arathyroidism, which develo# in

#atients with CKD that #rogresses to stage


9/17

RE*IEWSother

s#ecialists to focus on #atients with #rimary kidney

disease, #rogressive CKD and 56D.

+or all #atients with CKD, Cs should check for

drug interactions, environmental to-ins, and contrast B9"85 5G35A6 H NEP&RO'OG( GI8$5 H 98*86" !1 H <


+a%e . : Selected o-ser.ational studies of the ?uality of $rimary care for $atients with CK#

Stud! Design Popuation PeriodKe! resuts

Allen %etros$ecti.e 1** PCPs in 15 health centres in 2F N $atients were not testedyearly for urine $rotein, et al. cohort eastern &assachusetts, USA, caring 2+ *N had -lood$ressure 10+ mmHg, 25N were 211105 for 11, $atients with CK# eI(% not recei.ing a$$ro$riatetreatment with ACE

15F* mlmin1!0 m2" inhi-itors or A%/s and 2*N were recei.ing $otentially

harmful medicines

/oulware Cross4sectional 'ational, random, stratied sam$le 2F (amily $ractitioners 5*!2N" and generalinternists et al. ?uestionnaire" of ne$hrologists and + PCPs 25 !N" were less li8ely to recogniBeCK# than were 2*102 in the USA! %es$onses o-tained from ne$hrologists 3*!N" P J!1"

12* ne$hrologists and 1+ PCPs

Charles Cross4sectional Same $o$ulation as in the study 2F nly +N of ne$hrologists, 13N of

family $ractitioners, et al. ?uestionnaire" -y /oulwareet al. 2*" 25 and 00N of general

internists followed the K#

23100 guidelines on the la-oratory and radiological e.aluation

of $atients with CK# P J!1"

(o; et al. ualitati.e 1 PCPs from 1 health4care 'ot Awareness of K#guidelines was low, and PCPs 2*10 inter.iews facilities aOliated with the U$state stated oftenfa.oured less4accurate diagnostic tests for

'ew Tor8 Practice4-ased %esearch CK# serum creatinine"! Uncertainty e;isted a-out

'etwor8 the a$$ro$riate timing of referral to a ne$hrologist

srani Cross4sectional %andom sam$le of 1,55 US PCPs> 2 nly 05N of PCPs had Qade?uate8nowledgeR of CK# et al. ?uestionnaire" 1,50 eligi-le res$ondents! -ased on res$onses to 2

?uestions> for each2311 %es$onses o-tained from PCPs 14year increase in age of the PCP, the odds of

ha.ing ade?uate 8nowledge decreased -y 2*N

Lea et al. Cross4sectional PCPs in si; $redominantly 20 0N and 22N of PCPs did notidentify family history 2*101 sur.ey" African4American communities and African4Americanethnicity as ris8 factors for

in the USA! %es$onses o-tained CK#, res$ecti.ely! PCPs had high awareness that

from * PCPs hy$ertension and )2#& are $redictors of CK#

&inutolo Cross4sectional 'e$hrologists tertiary care" and 20 Patients with CK# cared for -yPCPs had higher et al. 03 PCPs caring for hy$ertensi.e -lood $ressure le.els than those caredfor -y a 2510+ $atients with CK# eI(% 15F* ml ne$hrologist P J!1"! )he ris8 of not attaining

min1!0 m2" in taly -lood $ressure target .alues was 2!*4times greater

in $rimary care than in tertiary care settings,

controlling for age, se;, )2#& and eI(%%a.era Cross4sectionalPCPs caring for ,5+2 hy$ertensi.e 25 nly 1!N of $atients with )2#& in this$o$ulation

et al. $atients with )2#& in taly achie.ed -lood $ressure J10+ mmHg! f231 $atients with eI(% J* mlmin1!0 m2, only 1N

had -een coded as ha.ing CK#

%a.era Cross4sectional PCPs caring for 03,525 25 nly 10!+N of $atients with eI(%J* ml et al. hy$ertensi.e $atients in taly min1!0 m2 and 2!*N of $atients with211103 nationally re$resentati.e sam$le eI(% J0 mlmin1!0 m2 were coded as ha.ing

of $atients" CK#! f $atients with eI(% J* mlmin1!0 m2,

only 5!N and 10!2N achie.ed -lood$ressure J13 mmHg and J10+

mmHg, res$ecti.ely

%aBa.ian Cross4sectional 'ationally4re$resentati.e, cluster4 2+ J1+N $atients werecorrectly diagnosed with CK#! et al. sur.ey" stratied sam$le of 50 PCPs in )he decisions -y PCPsnot to $rescri-e -lood 21210* Australia> res$onses o-tained from $ressure or li$id4lowering agentsfor $atients with

022 PCPs caring for ,3** $atients CK# only adhered to guideline recommendations in

age 55 years" with a.aila-le data 51N and *N of cases,

res$ecti.ely on 8idney function

A--re.iationsG ACE, angiotensin4con.erting enByme> A%/, angiotensin 4rece$tor -loc8er> CK#, chronic 8idney disease> eI(%, estimatedglomerular ltration rate> K#, Kidney #isease utcomes uality nitiati.e> PCP, $rimary care $hysician> )2#&, ty$e 2 dia-etes mellitus!


10/17

Primary care for cardiovascula

+ &,erc$se

+ -ea#t!* eat$ng

+ So/$ng cessat$on

+ #ood press"re g#*cae$c and #

Secondary care for CKD comp

+ reatent and anageent oand $nera# and one d$sord

+ "tr$t$on anageent

Multidisciplinary care for RR

+ S!ared dec$s$on a/$ng et

p!*s$c$ans and pat$ents

+ D$a#*s$s and6or /$dne*

transp#antat$on

+ S"rg$ca# creat$on

o

+ Ps*c!o#og$ca#

s"pport

P!ase 3CKD

stage 56&S)D;

P!ase 2

CKDstages4 65 ;

P!ase 1CKDstages

–3;1

RE*IEWSdyes that might cause acute kidney inNury. "hese factors could be

monitored with the hel# of information technology systems, which could,

for e-am#le, alert #hysicians to #otentially harmful drug combinations.

6ome #rescri#tion and over4the4counter medicines, such as B693Ds, can

#reci#itate acute kidney inNury in #atients with CKD, and can accelerate

#rogression of CKD.!7

CK#, chronic 8idney disease> ES%#, end4stage

renal disease> %%), renal re$lacement thera$y!

as risk factors for CKD, res#ectively.& Oigh

awareness that "!D$ and hy#ertension are

#redictors of CKD was, however, identified.!2 "hese

three surveys&,&&, were voluntary and had low

res#onse rates, ranging from 2.0: to &!.:. "he

#artici#ants of these studies might not be

re#resentative of the general C #o#ulation, and it

is #ossible that these findingsMwhich already #oint

to substantial room for im#rovementMoverstate the

'uality of CKD care ("able !).

+"e secondar! care mode

"imely involvement of renal s#ecialists is re'uired to

im#rove health outcomes for #atients with

#rogressive CKD. ayers, however, which are any

grou#s, other than #atients, that are res#onsible for

funding or reimbursing the cost of health care, want

to avoid unnecessary referral #atterns that could

de#lete resources. De#ending on the country, the

term #ayerF might refer to #rivate or #ublic insurers,

em#loyers, or other third4#arty #ayers.

9 systematic review of the clinical and cost4

effectiveness of early versus late (or no) referral to ane#hrologist found that an early referral is associated

with better health outcomes and might be more

costeffective than late referral.! C"s that #rovide

data on the clinical effectiveness of early referral

strategies were not identified. nly two studies

included #atients who were in the #redialysis stage,

and insufficient data were available on the natural

history of CKD and the costs and effects of early

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11/17

RE*IEWSreferral. "hese data highlight the re'uirement for long4term observational

studies of #atients with early4stage CKD to enhance delineation of

disease #rogression and the incidence of cardiovascular events in #atients

with and without associated health conditions, such as "!D$, #re4

e-isting cardiovascular disease, albuminuria or #roteinuria. +inally, the

authors of the systematic review suggested that the substantial costs of

early referral might be unaffordable for health4care systems, even if earlyreferral is cost4effective in the long term. +urther research is needed to

evaluate the costeffectiveness of im#roved #rimary care for #atients with

early4stage CKD.

5arly identification of CKD in the 8K is financially incentivized in

#rimary care, but some Cs e-#ress concern as to whether early CKD is

a genuine disease state across all ages.& 3n geogra#hical areas where

#atients are not correctly identified on CKD registers, cardiovascular

management is subo#timal, with worse control of blood #ressure and

cholesterol levels, com#ared to those #atients included on CKD

registers. 9 transition to a #rimary care model should be a universal

decision, unlike the develo#ment of current guidelines that have been

driven by secondary care #roviders.

Integrated care pat"/a!s for CKD

9 unified strategy for #atients across health4care #roviders and #ayers

might im#rove overall outcomes (=o- !). $odels of CKD care should be

evaluated in terms of value for money, and there must be an

understanding as to what a##roaches achieve a reliable service delivery

to high4risk #o#ulations. CKD can #rovide=o> . : Ser.ice deli.ery for CK#

Primar! care

J Patient assessment -y eI(% trend andor

traectory re$orting

J Classication of CK# -ased on ris8 of

$rogression

J dentication of CK# as an indicator of

ele.ated cardio.ascular ris8, with earlymodication of traditional ris8 factors

J Patient ad.ocacy and self4management

during earlystage 1F0" CK#

J %eferral to secondary care for s$ecialist

treatment of CK# com$lications

Secondar! care

J &ultidisci$linary management of disease

com$lications

J ngoing su$$ort for $atient

self4management $rogrammes

J ntegration with other secondary care

ser.ices to manage the -urden of

comor-idities

J PersonaliBed treatment goals withconsideration of ?uality of life

J ntegration into $rimary care to su$$ort

$eriodic monitoring of sta-le $atients -y

PCPs

J Structured follow4u$ for $atients ha.ing

e;$erienced AK, with data collection to

descri-e the long4term e=ects on I(%

traectory

A--re.iationsG AK, acute 8idney

inury> CK#, chronic 8idneydisease> eI(%, estimated

glomerular ltration rate> I(%,

glomerular ltration rate> PCP,

$rimary care $hysician!

a useful case study of how toenact a #rimary care model

that is oriented towards #ublic

health and that is #atient4

centred.

CKD care pat"/a!s in

t"e @SA

Des#ite the fragmentation of

the 86 health system,

im#rovements in CKD care

have been observed in #ublic

health4care organizations (for

e-am#le, the 3ndian Oealth6ervice0

6ervice with comorbid

hy#ertension and diabetes

mellitus were receiving an

9C5 inhibitor or 9=.2

=etween ;;2 and !112, the

mean haemoglobin 9c and

B9"85 5G35A6 H NEP&RO'OG( GI8$5 H 98*86" !1 H ))



12/17

RE*IEWSIDI cholesterol levels decreased from 7.0: to

2.7: and from &. mmol/l (!1 mg/dl) to !.

mmol/l (;0 mg/dl), res#ectively.7 "he age4

adNusted incidence of 56D among 9merican

3ndians with diabetes mellitus decreased by &:

(71. #er 1,111 diabetic #atients to .7 #er

1,111 diabetic #atients) between ;;1 and !11.

0

"he care strategies used by the 3ndian Oealth

6ervice have demonstrated that a system4wide

a##roach, even in an underfunded system, can

#roduce notable benefits in terms of cardiovascular

and renal health outcomes.

Kaiser ermanente of 6outhern California is a vertically4 integrated

health maintenance organization that has deviated from the KDE3

guidelines. "his organization instead a##lies a com#osite risk

assessment to target #atients whose conditions are e-#ected to worsen,

and it uses automated information technology systems that suggest

treatment o#tions based on in#utted #atient information. "he Oawaiian

network of Kaiser ermanente has also started to #rovide care to #atients

with CKD based on risk stratification, and has found that this a##roach is

associated with a statistically significant reduction in disease #rogression.1

CKD care pat"/a!s in t"e @K

*rowing integration between #rimary and secondary care is evident in

the 8K. 9 study #erformed in !11&M which #receded automated e*+

re#ortingMreviewed the electronic #rimary care records of ?&1,111

#atients and found a high rate of undiagnosed CKD, with >!1: of

#atients with an e*+ >&1 ml/min/.2& m ! being coded as having renal

disease.! 9lthough automated e*+ re#orting has im#roved the

detection of CKD in #rimary care and has increased referral rates, this

study suggests that it is #ossible to alert Cs about missed o##ortunities

for #reventive #rescribing.

9 model of CKD management similar to that introduced by Kaiser ermanente1 was initiated between !11& and !110 in the Aest $idlands,

8K. "he initial results show that #atient outcomes have im#roved as a

result of this care strategy, with a reduction in the #o#ulation4 adNusted

incidence of renal re#lacement thera#y.& 9nother study in Aest

Iincolnshire, 8K, evaluated the health outcomes of #atients with CKD

stages - : Wor8force, C), and other strategies to

im$ro.e care for early4stage CK#

Wor#force

J &oti.ated and educated wor8force and

$atient $o$ulation

J Easy access to la-oratory monitoring

J S$ecialist nursing sta= to su$$ort $atient

understanding of the disease

J (inancially .ia-le secondary care renal

ser.ices for a $otentially smaller -ut .ery ill

$atient $o$ulation PCPspeciaist interface

J &ulti4s$ecialty clinics in $rimary care to

su$$ort PCP education and $atient care

J #ened referral and

discharge criteria for

secondary care Roe of IC+

and decision2support

s!stems

J ntegration of $rimary and secondary care

records

J Accessi-le results re$orted to $atients in any

location

J Automated analysis of eI(% andor trends in

$roteinuria

J ncor$oration of .alidated $redicti.e models

for ES%# into la-oratory re$orts

J Electronic $rescri-ing lin8ed to -iochemical

results

&eat"2economic impact and "eat"2s!stem

5nancing

J Economic analyses -uilt into all studies of

CK# screening and treatment

J (inancial incenti.es -alanced towards

$re.ention of $rogression to ES%# J

Esta-lishment of CK# registries to $ermit

healthFeconomic analyses

'eaders"ip, go9ernance, and roe of

nationa and internationa organiBations

J nternational, e.idence4-ased accordance

-etween national and international -odies

regarding CK# screening and treatment

J ncreased data sharing -etween healthsystems of e$idemiologic trends in CK# J

Strong $atient re$resentation in all

organiBations

A--re.iationsG CK#, chronic 8idney disease> eI(%,

estimated glomerular ltration rate> ES%#,

end4stage renal disease> C), information and

communications technology> PCP, $rimary care

$hysician!

). H 98*86" !1 H GI8$5 ///0nature0com@ 215 &acmillan Pu-lishers Limited! All rights reser.ed


13/17

RE*IEWS&eat"2economic modeing of CKD

care

9s #reviously described, #hysicians should

consider the limitations of #o#ulation4based

e'uations to estimate *+ and instead evaluate

individual #atient characteristics when #redicting

disease risk and develo#ing treatment #lans.6tructured, early CKD intervention #rogrammes

can form the basis for such #ersonalized care.

*iven the heterogeneity of #atients with early4stage

CKD, and the variable risks in different

#o#ulations, clarity as to the a##ro#riate sco#e and

im#act of such #rogrammes is needed. Oealth4care

#roviders, #ayers and the general #ublic should be

made aware of the cost4effectiveness of investing

in CKD intervention #rogrammes (=o- &).

6ystems modelling is an ine-#ensive method to

study the effects of different interventions on

chronic disease outcomes and costs.2


14/17

RE*IEWSthera$ies! e!hrol. Dial. 0rans!lant.

)6 Su$$l! *", 01F1 1333"!

12! Sten.in8el, P! Chronic 8idney diseaseG

a $u-lic health $riority and har-inger

of $remature cardio.ascular disease! J.

#nt. )ed..8;, 5*F* 21"!

10! (eehally, D! et al. Early detection of

chronic 8idney disease! /)J --:,

a1*1+ 2+"!1! Le.in, A! V Ste.ens, P! E! Early

detection of CK#G the -enets,

limitations and e=ects on $rognosis!

at. Rev. e!hrol. :, *F5 211"!

15! Locatelli, (!, #el 9ecchio, L! V PoBBoni,

P! )he im$ortance of early detection of

chronic 8idney disease! e!hrol. Dial.

0rans!lant. ):, 2F 22"!

1*! El 'ahas, A! &! V /ello, A! K! Chronic

8idney diseaseG the glo-al challenge!(ancet -87, 001F0 25"!

1! 'ational Kidney (oundation! K#

Clinical

Practice Iuidelines for Chronic Kidney

#iseaseG

E.aluation, Classication andStratication! Am. J. Kidne" Dis. -


15/17

RE*IEWScreatinine in elderly indi.iduals! J. Am.

Soc. e!hrol. 21"!

5! Schae=ner, E! S! et al. )wo no.el

e?uations to estimate 8idney function in

$ersons aged years or older! Ann.

#ntern. )ed. )7:, 1F+1 212"!

5+! n8er, L! A! et al. Estimating glomerular

ltration rate from serum creatinine and

cystatin C! . 1ngl. J. )ed. -8:, 2F23212"!

53! n8er, L! A! et al. E;$ressing the CK#4EP

Chronic Kidney #isease E$idemiologyColla-oration" cystatin C e?uations for

estimating I(% with standardiBed

serum cystatin C .alues! Am. J. Kidne"

Dis. 7;, *+2F*+ 211"!

*! Saydah, S! H! et al. Al-uminuria

$re.alence in rst morning .oid

com$ared with $re.ious random urine

from adults in the 'ational Health and

'utrition E;amination Sur.ey, 23F

21 $lin. $hem. 7


16/17

RE*IEWSne$hro$athy! . 1ngl. J. )ed. -67, +*1F

+*3 21"!

33! %od-y, %! A! et al. )he r-esartan ty$e

dia-etic ne$hro$athy trialG study design

and -aseline $atient characteristics! (or

the Colla-orati.e Study Irou$! e!hrol.

Dial. 0rans!lant. )7, +F3 2"!

1! Sharma, P! et al. Angiotensin4con.erting

enByme inhi-itors and angiotensinrece$tor -loc8ers for adults with early

stage 1 to 0" non4dia-etic chronic

8idney disease! $ochrane Data8ase

S"st. Rev. ssue 1! Art! 'o!G C#51

htt$G

d;!doi!org1!121*51+5+!C# 51! $u-2!

11! Dager, K! D! V .an #i8, P! C! W! Has the

rise in the incidence of renalre$lacement thera$y in de.elo$ed

countries come to an end[ e!hrol.

Dial. 0rans!lant. .., *+F*+ 2"!

12! 9assalotti, D! A!, IracB4Weinstein, L!,

Iannon, &! %! V /rown, W! W! )argeted

screening and treatment of chronic

8idney diseaseG lessons learned from

the 8idney early e.aluation $rogram!

Dis. )anag. 7ealth Out. )6, 01F052 2*"!

10! KatB, ! D!, IerntholtB, )! E!, .an

#e.enter, &!, Schneider, H! V 'aic8er,

S! s there a need for early detection

$rogrammes for chronic 8idney

disease[ $lin. e!hrol. :6, S110FS11+

21"!

1! Lash, D! P! et al. Chronic %enal

nsuOciency Cohort C%C" StudyG

-aseline characteristics and

associations with 8idney function! $lin.

J.

Am. Soc. e!hrol. 6, 102F1011 23"!

15! (eldman, H! ! et al. )he Chronic %enal

nsuOciency Cohort C%C" studyG

design and methods! J. Am. Soc.

e!hrol. )6, S1+FS150 20"!

1*! Kronen-erg, (! Emerging ris8 factorsand mar8ers of chronic 8idney disease

$rogression!

at. Rev. e!hrol. 7, *F*+3 23"!

1! Dohnson, E! S!, Smith, #! H!, )hor$, &!

L!, Tang, \! H! V Duhaeri, D! Predicting

the ris8 of end4stage renal disease in

the $o$ulation4-ased settingG a

retros$ecti.e case4control study! /)$

e!hrol. )., 1 211"!

1+! Dohnson, E! S!, )hor$, &! L!, Platt, %! W!

V Smith, #! H! Predicting the ris8 of

dialysis and trans$lant among $atients

with CK#G a retros$ecti.e cohort study!

Am. J. Kid. Dis. 7., *50F** 2+"!

13! Le.in, A!, #urde., !, /eaulieu, &! V

Er, L! 9aria-ility and ris8 factors for

8idney disease $rogression and deathfollowing attainment of stage CK# in

a referred cohort! Am. J. Kid. Dis.

7., **1F*1 2+"!

11! &cClellan, W! &! V (landers, W! #! %is8

factors for $rogressi.e chronic 8idneydisease! J. Am. Soc. e!hrol. )6 Su$$l!

2", S*5FS 20"!

111! Peralta, C! A! et al. #etection of chronic8idney disease with creatinine, cystatin

C, and urine al-umin4to4creatinine ratio

and association with $rogression to

end4stage renal disease and mortality! JA)A -?7, 155F1552 211"!

112! &ahmoodi, /! K! et al. Associations of

8idney disease measures with mortality

and end4stage renal disease in

indi.iduals with and withouthy$ertensionG a meta4analysis! (ancet

-;?, 1*3F1**1 212"!

110! (o;, C! S! et al. Associations of 8idneydisease measures with mortality and

end4stage renal disease in indi.iduals

with and without dia-etesG a

meta4analysis! (ancet -;?, 1**2F1*0

212"!

11! %ose, I! Sic8 indi.iduals and sic8

$o$ulations!

#nt. J. 1!idemiol. -?, 2F02 21"!

115! Leoncini, I! et al. Ilo-al ris8

stratication in $rimary hy$ertensionG

the role of the 8idney! J. 7"!ertens. .8,2F02 2+"!

11*! Per8ins, %! &! et al. I(% #ecline and

&ortality %is8 among Patients with

Chronic Kidney #isease! $lin. J. Am.

Soc. e!hrol. 8, 1+3F1++* 211"!

11! Saweirs, W! W! &! V Ioddard, D! What

are the -est treatments for early

chronic 8idney disease[ A -ac8ground

$a$er $re$ared for the UK consensus

conference on early chronic 8idney

disease! e!hrol. Dial. 0rans!lant. ..,01F0+ 2"!

11+! Loud, (! V Iallagher, H! Kidney healthG

deli.ering e;cellence! Kidne" 7ealth

Re!ort 1F52 210"!

113! Shahinian, 9! /! V Saran, %! )he role of

$rimary care in the management of thechronic 8idney disease $o$ulation! Adv.

$hronic Kidne" Dis. ):, 2*F250

21"!

12! Le.in, A! )he need for o$timal and

coordinated management of CK#!Kidne" #nt. 8;, F1 25"!

121! /odenheimer, )!, Wagner, E! H! VIrum-ach, K! m$ro.ing $rimary care

for $atients with chronic illness! JA)A

.;;, 15F13 22"!

122! /odenheimer, )!, Wagner, E! H! V

Irum-ach, K! m$ro.ing $rimary care

for $atients with chronic illnessYthe

chronic care model, $art 2! JA)A .;;,

133F131 22"!

120! Wagner, E! H! Chronic disease

managementG what will it ta8e to

im$ro.e care for chronic illness[ 1


17/17

RE*IEWSty$e 2 dia-eticsG a $rimary care

$ers$ecti.e! e!hrol.

Dial 0rans!lant. .6, 152+F1500 23"!

11! srani, %! K!, Shea, D! A!, Do=e, &! &! V

(eldman, H! ! Physician characteristics

and 8nowledge of CK# management!

Am. J. Kidne" Dis. 76, 20+F2 23"!

12! /lac8, C! et al. Early referral strategies

for management of $eo$le with mar8ersof renal diseaseG a systematic re.iew of

the e.idence of clinical e=ecti.eness,

cost4e=ecti.eness and economic

analysis! 7ealth 0echnol. Assess. )6, 1F

1+ 21"!

10! Crinson, !, Iallagher, H!, )homas, '! V

de Lusignan, S! How ready is general

$ractice to im$ro.e ?uality in chronic

8idney disease[

A diagnostic analysis! /r. J. Gen. Pract.

8?, 0F3 21"!

1! Dain, P!, Cal.ert, &!, Coc8well, P! V

&c&anus, %! D! )he need for im$ro.ed

identication and accurate classication

of stages 0F5 chronic 8idney disease in

$rimary careG retros$ecti.e cohort

study! P(oS O1

Early chronic kidney disease diagnosis, management and models of care 2015.docx

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