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    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 [email protected] 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 )

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    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

    . H 98*86" !1 H GI8$5   ///[email protected] 215 &acmillan Pu-lishers Limited! All rights reser.ed

    http://www.nature.com/doifinder/10.1038/nrneph.2015.85http://www.nature.com/doifinder/10.1038/nrneph.2015.85http://www.nature.com/doifinder/10.1038/nrneph.2015.85

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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.

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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

    6 H 98*86" !1 H GI8$5   ///[email protected] 215 &acmillan Pu-lishers Limited! All rights reser.ed

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    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

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    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

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    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,

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    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

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    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 <

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    +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!

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    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

    )? H 98*86" !1 H GI8$5   ///[email protected] 215 &acmillan Pu-lishers Limited! All rights reser.ed

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

    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 ))

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

    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!

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

    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

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

    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. -

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

    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

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

    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

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    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