early chronic kidney disease diagnosis, management and models of care 2015.docx
TRANSCRIPT
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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 ?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#
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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
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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
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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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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,
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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
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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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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
$hysician!
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RE*IEWS&eat"2economic modeing of CKD
care
9s #reviously described, #hysicians should
consider the limitations of #o#ulation4based
e'uations to estimate *+ and instead evaluate
individual #atient characteristics when #redicting
disease risk and develo#ing treatment #lans.6tructured, early CKD intervention #rogrammes
can form the basis for such #ersonalized care.
*iven the heterogeneity of #atients with early4stage
CKD, and the variable risks in different
#o#ulations, clarity as to the a##ro#riate sco#e and
im#act of such #rogrammes is needed. Oealth4care
#roviders, #ayers and the general #ublic should be
made aware of the cost4effectiveness of investing
in CKD intervention #rogrammes (=o- &).
6ystems modelling is an ine-#ensive method to
study the effects of different interventions on
chronic disease outcomes and costs.2
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RE*IEWSthera$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. -
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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
-
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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