Updated: Sep 9, 2014

Practice Essentials
Chronic kidney disease (CKD is a co!!on condition in "hich there is a
loss o# kidney #$nction o%er ti!e& CKD is associated "ith an increased risk
o# cardio%asc$lar disease and chronic renal #ail$re& Kidney disease is the
ninth leadin' ca$se o# death in the United States&
Essential update: CAC score may be a superior predictor of CVE
risk, regardless of CKD status
(ccordin' to #indin's #ro! the )$lti*Ethnic St$dy o# (therosclerosis,
co!pared "ith carotid inti!a*!edia thickness (+), and ankle -rachial
inde. ((/+ (t"o !eas$res o# s$-clinical atherosclerosis, coronary artery
calci$! (C(C score !ay -e !ore predicti%e o# the risk #or cardio%asc$lar
e%ents (C0Es (coronary heart disease, stroke, heart #ail$re, peripheral
artery disease a!on' patients "ith and "itho$t CKD&
11, 22
Participants (a'ed
43*44 y incl$ded 1244 people "ith and 3259 "itho$t CKD, all "ith no
history o# cardio%asc$lar disease (C0D&
D$rin' a !edian #ollo"*$p o# 4&4 years, )ats$shita et al identi#ied 265 o#
530 cardio%asc$lar e%ents a!on' patients "ith CKD&
11, 22
(ltho$'h all three
!eas$res o# s$-clinical atherosclerosis "ere independently associated
"ith C0Es, ad7$sted ha8ard ratios (9:s "ere 'reater #or C(C scores (9:,
1&59 than those #or +), (9:, 1&12 and (/+ (9:, 1&20 in patients "ith and
those "itho$t CKD&
112
Signs and symptoms
Patients "ith CKD sta'es 1*6 (;<: =60 !>?!in?1&@6 !A are 'enerally
asy!pto!atic& ,ypically, it is not $ntil sta'es 4*3 (;<: B 60 !>?!in?1&@6
!A that endocrine?!eta-olic deran'e!ents or dist$r-ances in "ater or
electrolyte -alance -eco!e clinically !ani#est&
Si'ns o# !eta-olic acidosis in sta'e 3 CKD incl$de the #ollo"in':
Protein*ener'y !aln$trition
>oss o# lean -ody !ass
)$scle "eakness
Si'ns o# alterations in the "ay the kidneys are handlin' salt and "ater in
sta'e 3 incl$de the #ollo"in':
Peripheral ede!a
P$l!onary ede!a
9ypertension
(ne!ia in CKD is associated "ith the #ollo"in':
<ati'$e
:ed$ced e.ercise capacity
+!paired co'niti%e and i!!$ne #$nction
:ed$ced C$ality o# li#e
De%elop!ent o# cardio%asc$lar disease
De" onset o# heart #ail$re or the de%elop!ent o# !ore se%ere heart
#ail$re
+ncreased cardio%asc$lar !ortality
Ether !ani#estations o# $re!ia in end*sta'e renal disease (ES:D, !any
o# "hich are !ore likely in patients "ho are -ein' inadeC$ately dialy8ed,
incl$de the #ollo"in':
Pericarditis: Can -e co!plicated -y cardiac ta!ponade, possi-ly
res$ltin' in death
Encephalopathy: Can pro'ress to co!a and death
Peripheral ne$ropathy
:estless le' syndro!e
;astrointestinal sy!pto!s: (nore.ia, na$sea, %o!itin', diarrhea
Skin !ani#estations: Dry skin, pr$rit$s, ecchy!osis
<ati'$e, increased so!nolence, #ail$re to thri%e
)aln$trition
Erectile dys#$nction, decreased li-ido, a!enorrhea
Platelet dys#$nction "ith tendency to -leed
Screen ad$lt patients "ith CKD #or depressi%e sy!pto!sF sel#*report scales
at initiation o# dialysis therapy re%eal that 43G o# these patients ha%e s$ch
sy!pto!s, al-eit "ith a so!atic e!phasis&
See Clinical Presentation #or !ore detail&
Diagnosis
Laboratory studies
>a-oratory st$dies $sed in the dia'nosis o# CKD can incl$de the #ollo"in':
Co!plete -lood co$nt (C/C
/asic !eta-olic panel
Urinalysis
Ser$! al-$!in le%els: Patients !ay ha%e hypoal-$!ine!ia d$e to
$rinary protein loss or !aln$trition
>ipid pro#ile: Patients "ith CKD ha%e an increased risk o#
cardio%asc$lar disease
E%idence o# renal -one disease can -e deri%ed #ro! the #ollo"in' tests:
Ser$! phosphate
23*hydro.y%ita!in D
(lkaline phosphatase
+ntact parathyroid hor!one (P,9 le%els
+n certain cases, the #ollo"in' tests !ay also -e ordered as part o# the
e%al$ation o# patients "ith CKD:
Ser$! and $rine protein electrophoresis: Screen #or a !onoclonal
protein possi-ly representin' !$ltiple !yelo!a
(ntin$clear anti-odies ((D(, do$-le*stranded DD( anti-ody le%els:
Screen #or syste!ic l$p$s erythe!atos$s
Ser$! co!ple!ent le%els: :es$lts !ay -e depressed "ith so!e
'lo!er$lonephritides
Cytoplas!ic and perin$clear pattern antine$trophil cytoplas!ic
anti-ody (C*(DC( and P*(DC( le%els: Positi%e #indin's are help#$l in
the dia'nosis o# He'ener 'ran$lo!atosis and polyarteritis nodosaF P*
(DC( is also help#$l in the dia'nosis o# !icroscopic polyan'iitis
(ntiI'lo!er$lar -ase!ent !e!-rane (anti*;/) anti-odies:
Presence is hi'hly s$''esti%e o# $nderlyin' ;oodpast$re syndro!e
9epatitis / and C, h$!an i!!$node#iciency %ir$s (9+0, 0enereal
Disease :esearch >a-oratory (0D:> serolo'y: Conditions associated
"ith so!e 'lo!er$lonephritides
Imaging studies
+!a'in' st$dies that can -e $sed in the dia'nosis o# CKD incl$de the
#ollo"in':
:enal $ltrasono'raphy: Use#$l to screen #or hydronephrosis, "hich
!ay not -e o-ser%ed in early o-str$ction, or #or in%ol%e!ent o# the
retroperitone$! "ith #i-rosis, t$!or, or di##$se adenopathyF s!all,
echo'enic kidneys are o-ser%ed in ad%anced renal #ail$re
:etro'rade pyelo'raphy: Use#$l in cases "ith hi'h s$spicion #or
o-str$ction despite ne'ati%e renal $ltrasono'ra!s, as "ell as #or
dia'nosin' renal stones
Co!p$ted to!o'raphy (C, scannin': Use#$l to -etter de#ine renal
!asses and cysts $s$ally noted on $ltrasono'ra!sF also the !ost
sensiti%e test #or identi#yin' renal stones
)a'netic resonance i!a'in' ():+: Use#$l in patients "ho reC$ire a
C, scan -$t "ho cannot recei%e intra%eno$s contrastF relia-le in the
dia'nosis o# renal %ein thro!-osis
:enal radion$clide scannin': Use#$l to screen #or renal artery
stenosis "hen per#or!ed "ith captopril ad!inistrationF also C$antitates
the renal contri-$tion to the ;<:
Biopsy
Perc$taneo$s renal -iopsy is 'enerally indicated "hen renal i!pair!ent
and?or protein$ria approachin' the nephrotic ran'e are present and the
dia'nosis is $nclear a#ter appropriate "ork$p&
See Hork$p #or !ore detail&
Management
,he !edical care o# patients "ith CKD sho$ld #oc$s on the #ollo"in':
Delayin' or haltin' the pro'ression o# CKD: ,reat!ent o# the
$nderlyin' condition, i# possi-le, is indicated
,reatin' the patholo'ic !ani#estations o# CKD
,i!ely plannin' #or lon'*ter! renal replace!ent therapy
,he patholo'ic !ani#estations o# CKD sho$ld -e treated as #ollo"s:
(ne!ia: Hhen the he!o'lo-in le%el is -elo" 10 '?d>, treat "ith
erythropoiesis*sti!$latin' a'ents (ES(s, "hich incl$de epoetin al#a and
dar-epoetin al#a
9yperphosphate!ia: ,reat "ith dietary phosphate -inders and
dietary phosphate restriction
9ypocalce!ia: ,reat "ith calci$! s$pple!ents "ith or "itho$t
calcitriol
9yperparathyroidis!: ,reat "ith calcitriol or %ita!in D analo'$es
0ol$!e o%erload: ,reat "ith loop di$retics or $ltra#iltration
)eta-olic acidosis: ,reat "ith oral alkali s$pple!entation
Ure!ic !ani#estations: ,reat "ith lon'*ter! renal replace!ent
therapy (he!odialysis, peritoneal dialysis, or renal transplantation
+ndications #or renal replace!ent therapy incl$de the #ollo"in':
Se%ere !eta-olic acidosis
9yperkale!ia
Pericarditis
Encephalopathy
+ntracta-le %ol$!e o%erload
<ail$re to thri%e and !aln$trition
Peripheral ne$ropathy
+ntracta-le 'astrointestinal sy!pto!s
+n asy!pto!atic patients, a ;<: o# 3*9 !>?!in?1&@6 !A,
162
irrespecti%e
o# the ca$se o# the CKD or the presence or a-sence o# other
co!or-idities
,he Dational Kidney <o$ndationJs Kidney Disease E$tco!es K$ality
+nitiati%e (KDEK+ iss$ed a Clinical Practice ;$ideline #or D$trition in
Chronic :enal <ail$re, as "ell as a re%ision o# reco!!endations
#or D$trition in Children "ith Chronic Kidney Disease&
See ,reat!ent and )edication #or !ore detail&
Image library
,he tracin' sho"s a "ide K:S and %ery lar'e , "a%es& +n
the settin' o# a !ini!ally sy!pto!atic patient "ith renal #ail$re, this !$st -e treated as
hyperkale!ia $ntil the potassi$! le%el is not ele%ated& 9yperkale!ia !ay -e co!pletely
asy!pto!atic $ntil a lethal arrhyth!ia occ$rs& Calci$! salts are the !ost rapid actin' o#
the a'ents $sed to treat hyperkale!ia&
/ack'ro$nd
Chronic kidney disease (CKDLor chronic renal #ail$re (C:<, as it "as
historically ter!edLis a ter! that enco!passes all de'rees o# decreased
renal #$nction, #ro! da!a'edIat risk thro$'h !ild, !oderate, and se%ere
chronic kidney #ail$re& CKD is a "orld"ide p$-lic health pro-le!& +n the
United States, there is a risin' incidence and pre%alence o# kidney #ail$re,
"ith poor o$tco!es and hi'h cost (see Epide!iolo'y&
,he Kidney Disease E$tco!es K$ality +nitiati%e (KDEK+ o# the Dational
Kidney <o$ndation (DK< esta-lished a de#inition and classi#ication o# CKD&
142
,hese '$idelines ha%e allo"ed -etter co!!$nication a!on' physicians
and ha%e #acilitated inter%ention at the di##erent sta'es o# the disease&
,he KDEK+ de#ines CKD as either kidney da!a'e or a decreased
'lo!er$lar #iltration rate (;<: o# less than 50 !>?!in?1&@6 !
2
#or 6 or
!ore !onths& Hhate%er the $nderlyin' etiolo'y, once the loss o# nephrons
and red$ction o# #$nctional renal !ass reaches a certain point, the
re!ainin' nephrons -e'in a process o# irre%ersi-le sclerosis that leads to a
pro'ressi%e decline in the ;<:&
Staging
,he di##erent sta'es o# CKD #or! a contin$$!& ,he KDEK+ classi#ication o#
the sta'es o# CKD is as #ollo"s
142
:
Sta'e 1: Kidney da!a'e "ith nor!al or increased ;<: (=90
!>?!in?1&@6 !
2

Sta'e 2: )ild red$ction in ;<: (50*49 !>?!in?1&@6 !

2

Sta'e 6: )oderate red$ction in ;<: (60*39 !>?!in?1&@6 !

2

Sta'e 4: Se%ere red$ction in ;<: (13*29 !>?!in?1&@6 !

2

Sta'e 3: Kidney #ail$re (;<: B 13 !>?!in?1&@6 !

2
or dialysis
+n sta'e 1 and sta'e 2 CKD, red$ced ;<: alone does not clinch the
dia'nosis, -eca$se the ;<: !ay in #act -e nor!al or -orderline nor!al&
Ether !arkers o# kidney da!a'e, incl$din' a-nor!alities in the
co!position o# -lood or $rine or str$ct$ral a-nor!alities %is$ali8ed -y
i!a'in' st$dies, esta-lish the dia'nosis in s$ch cases& 9ypertension is a
#reC$ent si'n o# CKD -$t sho$ld not -y itsel# -e considered a !arker o# it,
-eca$se ele%ated -lood press$re is also co!!on a!on' people "itho$t
CKD&
+n an $pdate o# its CKD classi#ication syste!, the Dational Kidney
<o$ndation (DK< ad%ised that ;<: and al-$!in$ria le%els -e $sed
to'ether, rather than separately, to i!pro%e pro'nostic acc$racy in the
assess!ent o# CKD&
13, 52
)ore speci#ically, the '$idelines reco!!ended the
incl$sion o# esti!ated ;<: and al-$!in$ria le%els "hen e%al$atin' risks
#or o%erall !ortality, cardio%asc$lar disease, end*sta'e kidney #ail$re, ac$te
kidney in7$ry, and the pro'ression o# CKD& :e#erral to a kidney specialist
"as reco!!ended #or patients "ith a %ery lo" ;<: (B 13 !>?!in?1&@6 !A
or %ery hi'h al-$!in$ria (=600 !'?24 h&
13, 52
Patients "ith sta'es 1*6 CKD are #reC$ently asy!pto!atic& Clinical
!ani#estations res$ltin' #ro! lo" kidney #$nction typically appear in sta'es
4*3 (see Presentation&
reatment
Early dia'nosis and treat!ent o# the $nderlyin' ca$se and?or instit$tion o#
secondary pre%enti%e !eas$res is i!perati%e in patients "ith CKD& ,hese
!ay slo", or possi-ly halt, pro'ression o# the disease& ,he !edical care o#
patients "ith CKD (see ,reat!ent sho$ld #oc$s on the #ollo"in':
Slo"in' or haltin' the pro'ression o# CKD
,reatin' the patholo'ic !ani#estations o# CKD
,i!ely plannin' #or lon'*ter! renal replace!ent therapy, incl$din'
dialysis and transplantation
<or a disc$ssion o# CKD in children, click here&
Pathophysiolo'y
( nor!al kidney contains appro.i!ately 1 !illion nephrons, each o# "hich
contri-$tes to the total 'lo!er$lar #iltration rate (;<:& +n the #ace o# renal
in7$ry (re'ardless o# the etiolo'y, the kidney has an innate a-ility to
!aintain ;<:, despite pro'ressi%e destr$ction o# nephrons, as the
re!ainin' healthy nephrons !ani#est hyper#iltration and co!pensatory
hypertrophy& ,his nephron adapta-ility allo"s #or contin$ed nor!al
clearance o# plas!a sol$tes& Plas!a le%els o# s$-stances s$ch as $rea
and creatinine start to sho" !eas$ra-le increases only a#ter total ;<: has
decreased to 30G&
,he plas!a creatinine %al$e "ill appro.i!ately do$-le "ith a 30G
red$ction in ;<:& <or e.a!ple, a rise in plas!a creatinine #ro! a -aseline
%al$e o# 0&5 !'?d> to 1&2 !'?d> in a patient, altho$'h still "ithin the ad$lt
re#erence ran'e, act$ally represents a loss o# 30G o# #$nctionin' nephron
!ass&
,he hyper#iltration and hypertrophy o# resid$al nephrons, altho$'h
-ene#icial #or the reasons noted, has -een hypothesi8ed to represent a
!a7or ca$se o# pro'ressi%e renal dys#$nction& ,he increased 'lo!er$lar
capillary press$re !ay da!a'e the capillaries, leadin' initially to secondary
#ocal and se'!ental 'lo!er$losclerosis (<S;S and e%ent$ally to 'lo-al
'lo!er$losclerosis& ,his hypothesis is s$pported -y st$dies o# #i%e*si.ths
nephrecto!i8ed rats, "hich de%elop lesions identical to those o-ser%ed in
h$!ans "ith chronic kidney disease (CKD&
<actors other than the $nderlyin' disease process and 'lo!er$lar
hypertension that !ay ca$se pro'ressi%e renal in7$ry incl$de the #ollo"in':
Syste!ic hypertension
Dephroto.ins (e', nonsteroidal anti*in#la!!atory dr$'s 1DS(+Ds2,
intra%eno$s contrast !edia
Decreased per#$sion (e', #ro! se%ere dehydration or episodes o#
shock
Protein$ria (in addition to -ein' a !arker o# CKD
9yperlipide!ia
9yperphosphate!ia "ith calci$! phosphate deposition
S!okin'
Uncontrolled dia-etes
,haker et al #o$nd a stron' association -et"een episodes o# ac$te kidney
in7$ry ((K+ and c$!$lati%e risk #or the de%elop!ent o# ad%anced CKD in
!$ltiple hospitali8ed patients "ith dia-etes !ellit$s&
1@2
(ny (K+ %ers$s no
(K+ "as a risk #actor #or sta'e 4 CKD, and each additional (K+ episode
do$-led that risk&
1@2
<indin's #ro! the (therosclerosis :isk in Co!!$nities ((:+C St$dy, a
prospecti%e o-ser%ational cohort, s$''est that in#la!!ation and
he!ostasis are antecedent path"ays #or CKD&
142
,his st$dy $sed data #ro!
1@4@ cases o# CKD that de%eloped -et"een 194@ and 2004&
C!ild!ood renal function and CKD in c!ildren
+n children, the ;<: increases "ith a'e and is calc$lated "ith speci#ic
eC$ations that are di##erent than those #or ad$lts& (d7$sted #or -ody s$r#ace
area, the ;<: reaches ad$lt le%els -y a'e 2*6 years&
(spects o# pediatric kidney #$nction and the !eas$re o# creatinine are
in#or!ati%e not only #or children -$t also #or ad$lts& <or e.a!ple, it is
i!portant to reali8e that creatinine is deri%ed #ro! !$scle and, there#ore,
that children and s!aller indi%id$als ha%e lo"er creatinine le%els
independent o# the ;<:& ConseC$ently, la-oratory reports that do not
s$pply appropriate pediatric nor!al ran'es are !isleadin'& ,he sa!e is
tr$e #or indi%id$als "ho ha%e lo" !$scle !ass #or other reasons, s$ch as
!aln$trition, cache.ia, or a!p$tation&
(nother i!portant note #or childhood CKD is that physicians carin' #or
children !$st -e a"are o# nor!al -lood press$re le%els -y a'e, se., and
hei'ht& Pro!pt reco'nition o# hypertension at any a'e is i!portant,
-eca$se it !ay -e ca$sed -y pri!ary renal disease&
<ort$nately, CKD d$rin' childhood is rare and is $s$ally the res$lt o#
con'enital de#ects, s$ch as posterior $rethral %al%es or dysplastic kidney
!al#or!ations& (nother co!!on ca$se is <S;S& ;enetic kidney diseases
are also #reC$ently !ani#ested in childhood CKD& (d%ances in pediatric
nephrolo'y ha%e ena-led 'reat leaps in s$r%i%al #or pediatric CKD and end*
sta'e renal disease (ES:D, incl$din' #or children "ho need dialysis or
transplantation&
Aging and renal function
,he -iolo'ic process o# a'in' initiates %ario$s str$ct$ral and #$nctional
chan'es "ithin the kidney&
19, 102
:enal !ass pro'ressi%ely declines "ith
ad%ancin' a'e, and 'lo!er$losclerosis leads to a decrease in renal "ei'ht&
9istolo'ic e.a!ination is nota-le #or a decrease in 'lo!er$lar n$!-er o# as
!$ch as 60*30G -y a'e @0 years& ,he ;<: peaks d$rin' the third decade
o# li#e at appro.i!ately 120 !>?!in?1&@6 !
2
F it then $nder'oes an ann$al
!ean decline o# appro.i!ately 1 !>?!in?y?1&@6 !
2
, reachin' a !ean %al$e
o# @0 !>?!in?1&@6 !
2
at a'e @0 years&
+sche!ic o-solescence o# cortical 'lo!er$li is predo!inant, "ith relati%e
sparin' o# the renal !ed$lla& M$.ta!ed$llary 'lo!er$li see a sh$ntin' o#
-lood #ro! a##erent to e##erent arterioles, res$ltin' in redistri-$tion o# -lood
#lo" #a%orin' the renal !ed$lla& ,hese anato!ic and #$nctional chan'es in
renal %asc$lat$re appear to contri-$te to an a'e*related decrease in renal
-lood #lo"&
:enal he!odyna!ic !eas$re!ents in a'ed h$!ans and ani!als s$''est
that altered #$nctional response o# the renal %asc$lat$re !ay -e an
$nderlyin' #actor in di!inished renal -lood #lo" and increased #iltration
noted "ith pro'ressi%e renal a'in'& ,he %asodilatory response is -l$nted in
the elderly "hen co!pared to yo$n'er patients&
9o"e%er, the %asoconstrictor response to intrarenal an'iotensin is identical
in yo$n' and older h$!an s$-7ects& ( -l$nted %asodilatory capacity "ith
appropriate %asoconstrictor response !ay indicate that the a'ed kidney is
in a state o# %asodilatation to co!pensate #or the $nderlyin' sclerotic
da!a'e&
;i%en the histolo'ic e%idence #or nephronal senescence "ith a'e, a decline
in the ;<: is e.pected& 9o"e%er, a "ide %ariation in the rate o# ;<:
decline is reported -eca$se o# !eas$re!ent !ethods, race, 'ender,
'enetic %ariance, and other risk #actors #or renal dys#$nction&
"enetics
)ost cases o# CKD are acC$ired rather than inherited, altho$'h CKD in a
child is !ore likely to ha%e a 'enetic or inherited ca$se& Hell*descri-ed
'enetic syndro!es associated "ith CKD incl$de a$toso!al do!inant
polycystic kidney disease((DPKD and (lport syndro!e& Ether e.a!ples
o# speci#ic sin'le*'ene or #e"*'ene !$tations associated "ith CKD incl$de
Dent disease, nephronophthisis, and atypical he!olytic $re!ic syndro!e
(9US&
APOL1 gene
)ore recently, researchers ha%e -e'$n to identi#y 'enetic contri-$tions to
increased risk #or de%elop!ent or pro'ression o# CKD& <ried!an et al
#o$nd that !ore than 6 !illion -lack persons "ith 'enetic %ariants in -oth
copies o# apolipoprotein >1 (APOL1 are at hi'her risk #or hypertension*
attri-$ta-le ES:D and <S;S& +n contrast, -lack indi%id$als "itho$t the risk
'enotype and E$ropean (!ericans appear to ha%e si!ilar risk #or
de%elopin' nondia-etic CKD&
1112
FGF-23 gene
Circ$latin' le%els o# the phosphate*re'$latin' hor!one #i-ro-last 'ro"th
#actor 26 (<;<*26 are a##ected -y %ariants in the FGF23 'ene& +sako%a et
al reported that ele%ated <;<*26 le%els are an independent risk #actor #or
ES:D in patients "ho ha%e #airly "ell*preser%ed kidney #$nction (sta'es 2*
4 and #or !ortality across the scope o# CKD&
1122
Single-nucleotide polymorpisms
( re%ie" o# 15 sin'le*n$cleotide poly!orphis!s (SDPs that had -een
associated "ith %ariation in ;<: #o$nd that de%elop!ent o# al-$!in$ria
"as associated !ostly "ith an SDP in the S!"OO#3 'ene&
1162
E%en
acco$ntin' #or this %ariant, ho"e%er, there is e%idence that so!e $nkno"n
'enetic %ariant in#l$ences the de%elop!ent o# al-$!in$ria in CKD& ,his
st$dy also s$''ests a separate 'enetic in#l$ence on de%elop!ent o#
al-$!in$ria %ers$s red$ction in ;<:&
1162
( 'eno!e*"ide association st$dy (;H(S that incl$ded o%er 160,000
patients #o$nd 5 SDPs associated "ith red$ced ;<:, located in or
near #PP$%2, %%&1,SL'()A1, '%*12, 'ASP+, and I,O-.&
1142
,he SDP
in SL'()A1 "as associated "ith decreased ;<: in nondia-etic
indi%id$als, "hereas SDPs located in the%,A/'10 and '%*12 'enes "ere
associated "ith decreased ;<: in indi%id$als yo$n'er than 53 years&
1142
Immune-system and "AS genes
( n$!-er o# 'enes ha%e -een associated "ith the de%elop!ent o# ES:D&
)any o# these 'enes in%ol%e aspects o# the i!!$ne syste!
(e', ''"3, IL1",, IL(&
1132
Uns$rprisin'ly, poly!orphis!s in 'enes in%ol%in' the renin*an'iotensin
syste! (:(S ha%e also -een i!plicated in predisposition to CKD& Ene
st$dy #o$nd that patients "ith CKD "ere si'ni#icantly !ore likely to ha%e
the (2630; poly!orphis! in the A'$ 'ene, "hich encodes the
an'iotensin*con%ertin' en8y!e ((CE&
1152
,hey "ere also !ore likely to ha%e
the C3@6, poly!orphis! in the AG1"1 'ene, "hich encodes the
an'iotensin ++ type 1 receptor&
1152
#yperkalemia
,he a-ility to !aintain potassi$! e.cretion at near*nor!al le%els is
'enerally !aintained in CKD, as lon' as aldosterone secretion and distal
#lo" are !aintained& (nother de#ense a'ainst potassi$! retention in
patients "ith CKD is increased potassi$! e.cretion in the 'astrointestinal
tract, "hich also is $nder control o# aldosterone&
9yperkale!ia $s$ally does not de%elop $ntil the ;<: #alls to less than 20*
23 !>?!in?1&@6 !A, at "hich point the kidneys ha%e decreased a-ility to
e.crete potassi$!& 9yperkale!ia can -e o-ser%ed sooner in patients "ho
in'est a potassi$!*rich diet or ha%e lo" ser$! aldosterone le%els&
Co!!on so$rces o# lo" aldosterone le%els are dia-etes !ellit$s and the
$se o# (CE inhi-itors or DS(+Ds&
9yperkale!ia in CKD can -e a''ra%ated -y an e.tracell$lar shi#t o#
potassi$!, s$ch as occ$rs in the settin' o# acide!ia or #ro! lack o# ins$lin&
#ypokalemia
9ypokale!ia is $nco!!on -$t can de%elop in patients "ith %ery poor
intake o# potassi$!, 'astrointestinal or $rinary loss o# potassi$!, or
diarrhea or in patients "ho $se di$retics&
Metabolic acidosis
)eta-olic acidosis o#ten is a !i.t$re o# nor!al anion 'ap and increased
anion 'apF the latter is o-ser%ed 'enerally "ith sta'e 3 CKD -$t "ith the
anion 'ap 'enerally not hi'her than 20 !EC?>& +n CKD, the kidneys are
$na-le to prod$ce eno$'h a!!onia in the pro.i!al t$-$les to e.crete the
endo'eno$s acid into the $rine in the #or! o# a!!oni$!& +n sta'e 3 CKD,
acc$!$lation o# phosphates, s$l#ates, and other or'anic anions are the
ca$se o# the increase in anion 'ap&
)eta-olic acidosis has -een sho"n to ha%e deleterio$s e##ects on protein
-alance, leadin' to the #ollo"in':
De'ati%e nitro'en -alance
+ncreased protein de'radation
+ncreased essential a!ino acid o.idation
:ed$ced al-$!in synthesis
>ack o# adaptation to a lo"*protein diet
9ence, !eta-olic acidosis is associated "ith protein*ener'y !aln$trition,
loss o# lean -ody !ass, and !$scle "eakness& ,he !echanis! #or
red$cin' protein !ay incl$de e##ects on adenosine triphosphate ((,PI
dependent $-iC$itin proteaso!es and increased acti%ity o# -ranched*chain
keto acid dehydro'enases&
)eta-olic acidosis also leads to an increase in #i-rosis and rapid
pro'ression o# kidney disease, -y ca$sin' an increase in a!!onia'enesis
to enhance hydro'en e.cretion&
+n addition, !eta-olic acidosis is a #actor in the de%elop!ent o# renal
osteodystrophy, -eca$se -one acts as a -$##er #or e.cess acid, "ith
res$ltant loss o# !ineral& (cidosis !ay inter#ere "ith %ita!in D !eta-olis!,
and patients "ho are persistently !ore acidotic are !ore likely to ha%e
osteo!alacia or lo"*t$rno%er -one disease&
Salt$ and %ater$!andling abnormalities
Salt and "ater handlin' -y the kidney is altered in CKD& E.tracell$lar
%ol$!e e.pansion and total*-ody %ol$!e o%erload res$lts #ro! #ail$re o#
sodi$! and #ree*"ater e.cretion& ,his 'enerally -eco!es clinically
!ani#ested "hen the ;<: #alls to less than 10*13 !>?!in?1&@6 !A, "hen
co!pensatory !echanis!s ha%e -eco!e e.ha$sted&
(s kidney #$nction declines #$rther, sodi$! retention and e.tracell$lar
%ol$!e e.pansion lead to peripheral ede!a and, not $nco!!only,
p$l!onary ede!a and hypertension& (t a hi'her ;<:, e.cess sodi$! and
"ater intake co$ld res$lt in a si!ilar pict$re i# the in'ested a!o$nts o#
sodi$! and "ater e.ceed the a%aila-le potential #or co!pensatory
e.cretion&
,$-$lointerstitial renal diseases represent the !inority o# cases o# CKD&
9o"e%er, it is i!portant to note that s$ch diseases o#ten ca$se #l$id loss
rather than o%erload& ,h$s, despite !oderate or se%ere red$ctions in ;<:,
t$-$lointerstitial renal diseases !ay !ani#est #irst as poly$ria and %ol$!e
depletion, "ith ina-ility to concentrate the $rine& ,hese sy!pto!s !ay -e
s$-tle and reC$ire close attention to -e reco'ni8ed& 0ol$!e o%erload
occ$rs only "hen ;<: red$ction -eco!es %ery se%ere&
Anemia
Dor!ochro!ic nor!ocytic ane!ia principally de%elops #ro! decreased
renal synthesis o# erythropoietin, the hor!one responsi-le #or -one !arro"
sti!$lation #or red -lood cell (:/C prod$ction& ,he ane!ia starts early in
the co$rse o# the disease and -eco!es !ore se%ere as, "ith the shrinkin'
a%aila-ility o# %ia-le renal !ass, the ;<: pro'ressi%ely decreases&
Do retic$locyte response occ$rs& :/C s$r%i%al is decreased, and -leedin'
tendency is increased #ro! the $re!ia*ind$ced platelet dys#$nction& Ether
ca$ses o# ane!ia in CKD incl$de the #ollo"in':
Chronic -lood loss: Ure!ia*ind$ced platelet dys#$nction enhances
-leedin' tendency
Secondary hyperparathyroidis!
+n#la!!ation
D$tritional de#iciency
(cc$!$lation o# inhi-itors o# erythropoiesis
&one disease
:enal -one disease is a co!!on co!plication o# CKD& +t res$lts in skeletal
co!plications (e', a-nor!ality o# -one t$rno%er, !inerali8ation, linear
'ro"th and e.traskeletal co!plications (e', %asc$lar or so#t*tiss$e
calci#ication&
Di##erent types o# -one disease occ$r "ith CKD, as #ollo"s:
9i'h*t$rno%er -one disease #ro! hi'h parathyroid hor!one (P,9
le%els
>o"*t$rno%er -one disease (adyna!ic -one disease
De#ecti%e !inerali8ation (osteo!alacia
)i.ed disease
/eta*2*!icro'lo-$linIassociated -one disease
/one disease in children is si!ilar -$t occ$rs d$rin' 'ro"th& ,here#ore,
children "ith CKD are at risk #or short stat$re, -one c$r%at$re, and poor
!inerali8ation (Nrenal ricketsO is the eC$i%alent ter! #or ad$lt osteo!alacia&
CKDI!ineral and -one disorder (CKD*)/D in%ol%es -ioche!ical
a-nor!alities related to -one !eta-olis!& CKD*)/D !ay res$lt #ro!
alteration in le%els o# ser$! phosphor$s, P,9, %ita!in D, and alkaline
phosphatase&
Secondary hyperparathyroidis! de%elops in CKD -eca$se o# the #ollo"in'
#actors:
9yperphosphate!ia
9ypocalce!ia
Decreased renal synthesis o# 1,23*dihydro.ycholecalci#erol (1,23*
dihydro.y%ita!in D, or calcitriol
+ntrinsic alteration in the parathyroid 'lands, "hich 'i%es rise to
increased P,9 secretion and increased parathyroid 'ro"th
Skeletal resistance to P,9
Calci$! and calcitriol are pri!ary #eed-ack inhi-itorsF hyperphosphate!ia
is a sti!$l$s to P,9 synthesis and secretion&
!yperpospatemia and ypocalcemia
Phosphate retention -e'ins in early CKDF "hen the ;<: #alls, less
phosphate is #iltered and e.creted, -$t -eca$se o# increased P,9
secretion, "hich increases renal e.cretion, ser$! le%els do not rise initially&
(s the ;<: #alls to"ard CKD sta'es 4*3, hyperphosphate!ia de%elops
#ro! the ina-ility o# the kidneys to e.crete the e.cess dietary intake&
9yperphosphate!ia s$ppresses the renal hydro.ylation o# inacti%e 23*
hydro.y%ita!in D to calcitriol, so ser$! calcitriol le%els are lo" "hen the
;<: is less than 60 !>?!in?1&@6 !A& +ncreased phosphate concentration
also e##ects P,9 concentration -y its direct e##ect on the parathyroid 'lands
(posttranscriptional e##ect&
9ypocalce!ia de%elops pri!arily #ro! decreased intestinal calci$!
a-sorption -eca$se o# lo" plas!a calcitriol le%els& +t also possi-ly res$lts
#ro! increased calci$!*phosphate -indin', ca$sed -y ele%ated ser$!
phosphate le%els&
Increased P1! secretion
>o" ser$! calcitriol le%els, hypocalce!ia, and hyperphosphate!ia ha%e all
-een de!onstrated to independently tri''er P,9 synthesis and secretion&
(s these sti!$li persist in CKD, partic$larly in the !ore ad%anced sta'es,
P,9 secretion -eco!es !aladapti%e, and the parathyroid 'lands, "hich
initially hypertrophy, -eco!e hyperplastic& ,he persistently ele%ated P,9
le%els e.acer-ate hyperphosphate!ia #ro! -one resorption o# phosphate&
S2eletal mani3estations
+# ser$! le%els o# P,9 re!ain ele%ated, a hi'h -one t$rno%er lesion,
kno"n as osteitis #i-rosa, de%elops& ,his is one o# se%eral -one lesions,
"hich as a 'ro$p are co!!only kno"n as renal osteodystrophy and "hich
de%elop in patients "ith se%ere CKD& Esteitis #i-rosa is co!!on in patients
"ith ES:D&
,he pre%alence o# adyna!ic -one disease in the United States has
increased, and it has -een descri-ed -e#ore the initiation o# dialysis in
so!e cases& ,he patho'enesis o# adyna!ic -one disease is not "ell
de#ined, -$t se%eral #actors !ay contri-$te, incl$din' hi'h calci$! load,
$se o# %ita!in D sterols, increasin' a'e, pre%io$s corticosteroid therapy,
peritoneal dialysis, and increased le%el o# D*ter!inally tr$ncated P,9
#ra'!ents&
>o"*t$rno%er osteo!alacia in the settin' o# CKD is associated "ith
al$!in$! acc$!$lation& +t is !arkedly less co!!on than hi'h*t$rno%er
-one disease&
(nother #or! o# -one disease is dialysis*related a!yloidosis, "hich is no"
$nco!!on in the era o# i!pro%ed dialysis !e!-ranes& ,his condition
occ$rs #ro! -eta*2*!icro'lo-$lin acc$!$lation in patients "ho ha%e
reC$ired chronic dialysis #or at least 4*10 years& +t !ani#ests "ith cysts at
the ends o# lon' -ones&
Etiolo'y
Ca$ses o# chronic kidney disease (CKD incl$de the #ollo"in':
Dia-etic kidney disease
9ypertension
0asc$lar disease
;lo!er$lar disease (pri!ary or secondary
Cystic kidney diseases
,$-$lointerstitial disease
Urinary tract o-str$ction or dys#$nction
:ec$rrent kidney stone disease
Con'enital (-irth de#ects o# the kidney or -ladder
Unreco%ered ac$te kidney in7$ry
0asc$lar diseases that can ca$se CKD incl$de the #ollo"in':
:enal artery stenosis
Cytoplas!ic pattern antine$trophil cytoplas!ic anti-ody (C*(DC(I
positi%e and perin$clear pattern antine$trophil cytoplas!ic anti-ody (P*
(DC(Ipositi%e %asc$litides
(DC(*ne'ati%e %asc$litides
(theroe!-oli
9ypertensi%e nephrosclerosis
:enal %ein thro!-osis
Pri!ary 'lo!er$lar diseases incl$de the #ollo"in':
)e!-rano$s nephropathy
(lport syndro!e
+!!$no'lo-$lin ( (+'( nephropathy
<ocal and se'!ental 'lo!er$losclerosis (<S;S
)ini!al chan'e disease
)e!-ranoproli#erati%e 'lo!er$lonephritis ()P;D
Co!ple!ent*related diseases (e', atypical he!olytic*$re!ic
syndro!e 19US2, dense deposit disease
:apidly pro'ressi%e (crescentic 'lo!er$lonephritis
Secondary ca$ses o# 'lo!er$lar disease incl$de the #ollo"in':
Dia-etes !ellit$s
Syste!ic l$p$s erythe!atos$s
:he$!atoid arthritis
)i.ed connecti%e tiss$e disease
Scleroder!a
He'ener 'ran$lo!atosis
)i.ed cryo'lo-$line!ia
Endocarditis
9epatitis / and C
Syphilis
9$!an i!!$node#iciency %ir$s (9+0
Parasitic in#ection
9eroin $se
;old
Penicilla!ine
(!yloidosis
>i'ht*chain deposition disease
Deoplasia
,hro!-otic thro!-ocytopenic p$rp$ra (,,P
Shi'a*to.in or Streptococcus pneumoniae I related 9US
9enoch*SchPnlein p$rp$ra
:e#l$. nephropathy
Ca$ses o# t$-$lointerstitial disease incl$de the #ollo"in':
Dr$'s (e', s$l#ona!ides, allop$rinol
+n#ection (%iral, -acterial, parasitic
S7P'ren syndro!e
,$-$lointerstitial nephritis and $%eitis (,+DU syndro!e
Chronic hypokale!ia
Chronic hypercalce!ia
Sarcoidosis
)$ltiple !yelo!a cast nephropathy
9ea%y !etals
:adiation nephritis
Polycystic kidneys
Cystinosis and other inherited diseases
Urinary tract o-str$ction !ay res$lt #ro! any o# the #ollo"in':
/eni'n prostatic hypertrophy
Urolithiasis (kidney stones
Urethral strict$re
,$!ors
De$ro'enic -ladder
Con'enital (-irth de#ects o# the kidney or -ladder
:etroperitoneal #i-rosis
Epide!iolo'y
+n the United States, the Dational +nstit$te o# Dia-etes and Di'esti%e and
Kidney Diseases (D+DDK reports that 1 in 10 (!erican ad$lts has so!e
le%el o# chronic kidney disease (CKD&
11@2
Kidney disease is the ninth leadin'
ca$se o# death in the United States&
1142
(ccordin' to the D+DDK, the incidence o# reco'ni8ed CKD in people a'ed
20*54 years in the United States rose only sli'htly #ro! 2000 2004 and
re!ains less than 0&3G&
11@2
+n contrast, the incidence o# reco'ni8ed CKD in
people a'ed 53 years or older !ore than do$-led -et"een 2000 and 2004,
#ro! appro.i!ately 1&4G to appro.i!ately 4&6G&
11@2
,he US pre%alence o# CKD increases dra!atically "ith a'e (4G at a'e 29*
69 yF 4@G at a'e =@0 y, "ith the !ost rapid 'ro"th in people a'ed 50
years or older& +n the Dational 9ealth and D$trition E.a!ination S$r%ey
(D9(DES st$dy, the pre%alence o# sta'e 6 CKD in this a'e 'ro$p rose
#ro! 14&4G d$rin' the years 1944 1994 to 24&3G d$rin' the years 2006*
2005& D$rin' the sa!e period, the pre%alence o# CKD in people a'ed 20*
69 years re!ained consistently -elo" 0&3G&
11@2
(ccordin' to 1999 2004 D9(DES data, the esti!ated pre%alence o# CKD
-y sta'e "as as #ollo"s
1192
:
Sta'e 1: 3&@G
Sta'e 2: 3&4G
Sta'e 6: 3&4G
Sta'e 4: 0&4G
Sta'e 3: 0&4G
,he US incidence o# end*sta'e renal disease (ES:D rose steadily #ro!
1940*2001, -$t the rate s$-seC$ently le%eled o## at appro.i!ately 630 per
1 !illion pop$lation&
11@2
9o"e%er, the percenta'e o# patients older than 53
years has -een the !ost rapidly 'ro"in' se'!ent o# the ES:D pop$lation,
ha%in' increased #ro! 3G to 6@G o# this 'ro$p&
11@2
,he US S$r'eon ;eneralJs latest report on 10*year national o-7ecti%es #or
i!pro%in' the health o# all (!ericans, 9ealthy People 2020, contains a
chapter #oc$sed onCKD& <or 2020, 9ealthy People lays o$t 14 o-7ecti%es
concernin' red$ction o# the US incidence, !or-idity, !ortality, and health
costs o# CKD& :ed$cin' renal #ail$re "ill reC$ire additional p$-lic health
e##orts, incl$din' e##ecti%e pre%enti%e strate'ies and early detection and
treat!ent o# CKD&
'ace$related demograp!ics
(ltho$'h CKD a##ects all races, the incidence rate o# ES:D a!on' -lacks
in the United States is nearly 4 ti!es that #or "hites&
11@2
Choi et al #o$nd that
rates o# ES:D a!on' -lack patients e.ceeded those a!on' "hite patients
at all le%els o# -aseline esti!ated 'lo!er$lar #iltration rate (;<:&
1202
:isk o#
ES:D a!on' -lack patients "as hi'hest at an esti!ated ;<: o# 43*39
!>?!in?1&@6 !
2
, as "as the risk o# !ortality&
Schold et al #o$nd that a!on' -lack kidney transplant recipients, rates o#
'ra#t loss and ac$te re7ection "ere hi'her than in "hite recipients,
especially a!on' yo$n'er patients&
1212
9icks et al looked at the connection
-et"een -lack patients "ith the sickle cell trait and their increased risk #or
kidney diseaseF the st$dy #o$nd that sickle cell trait "as not associated "ith
dia-etic or nondia-etic ES:D in a lar'e sa!ple o# -lack patients&
1222
+!portant di##erences also e.ist in the #reC$ency o# speci#ic ca$ses o# CKD
a!on' di##erent races& +n the Chronic Kidney Disease in Children (CKiD
St$dy, #or e.a!ple, 'lo!er$lar disease "as !$ch !ore co!!on a!on'
non"hite persons&
1262
E%erall, <S;S in partic$lar is !ore co!!on a!on'
9ispanic (!ericans and -lack persons, as is the risk o# nephropathy "ith
dia-etes or "ith hypertensionF in contrast, +'( nephropathy is rare in -lack
indi%id$als and !ore co!!on a!on' those "ith (sian ancestry&
1242
Se($ related demograp!ics
+n D9(DES, the distri-$tion o# esti!ated ;<:s #or the sta'es o# CKD "as
si!ilar in -oth se.es& +n the United States :enal Data Syste! (US:DS
2011 (nn$al Data :eport, ho"e%er, the incident rate o# ES:D cases at the
initiation o# he!odialysis in 2009 "as hi'her #or !ales, "ith 413&1 per
!illion pop$lation co!pared "ith 235&5 #or #e!ales&
1232
CKD in children is so!e"hat !ore co!!on in -oys, -eca$se posterior
$rethral %al%es, the !ost co!!on -irth de#ect leadin' to CKD, occ$r only in
-oys& +!portantly, !any indi%id$als "ith con'enital kidney disease s$ch as
dysplasia or hypoplasia do not clinically !ani#est CKD or ES:D $ntil
ad$lthood&
Pro'nosis
Patients "ith chronic kidney disease (CKD 'enerally e.perience
pro'ressi%e loss o# kidney #$nction and are at risk #or end*sta'e renal
disease (ES:D& ,he rate o# pro'ression depends on a'e, the $nderlyin'
dia'nosis, the s$ccess o# i!ple!entation o# secondary pre%enti%e
!eas$res, and the indi%id$al patient& ,i!ely initiation o# chronic renal
replace!ent therapy is i!perati%e to pre%ent the $re!ic co!plications o#
CKD that can lead to si'ni#icant !or-idity and death&
,an'ri et al de%eloped and %alidated a !odel in ad$lt patients that $ses
ro$tine la-oratory res$lts to predict pro'ression #ro! CKD (sta'es 6*3 to
kidney #ail$re&
1252
,hey reported that lo"er esti!ated 'lo!er$lar #iltration rate
(;<:, hi'her al-$!in$ria, yo$n'er a'e, and !ale se. pointed to a #aster
pro'ression o# kidney #ail$re& (lso, a lo"er ser$! al-$!in, calci$!, and
-icar-onate le%el and a hi'her ser$! phosphate le%el "ere #o$nd to predict
an ele%ated risk o# kidney #ail$re&
1252
#ospitali)ation
Unad7$sted rates o# hospitali8ation in the CKD pop$lation, re#lectin' its total
disease -$rden, are 6*3 ti!es hi'her than those o# patients "itho$t CKD&
1232
(#ter ad7$st!ent #or 'ender, prior hospitali8ations, and co!or-idity, rates
#or patients "ith CKD are 1&4 ti!es hi'her& :ates o# hospitali8ation #or
cardio%asc$lar disease and -acterial in#ection are partic$larly ele%ated&
1232
Dialysis
+n the United States, he!odialysis and peritoneal dialysis patients a%era'e
2 hospital ad!issions per yearF patients "ho ha%e a renal transplant
a%era'e 1 hospital ad!ission per year& (dditionally, patients "ith ES:D
"ho $nder'o renal transplantation s$r%i%e lon'er than those on lon'*ter!
dialysis&
12@2
9e!odialysis per#or!ed 5 ti!es per "eek si'ni#icantly increased the risk o#
%asc$lar access co!plications co!pared "ith a con%entional 6*day
re'i!en in one st$dy&
124, 292
E# 123 patients "ho recei%ed he!odialysis 5
days per "eek, 44 e.perienced the co!posite pri!ary endpoint e%ent o#
%asc$lar repair, loss, or related hospitali8ation, co!pared "ith only 29 o#
the 120 patients $nder'oin' con%entional treat!ent& :es$lts indicated that
o%erall risk #or a #irst access e%ent "as @5G hi'her "ith daily he!odialysis
than "ith the con%entional re'i!en&
124, 292
Mortality
,he !ortality rates associated "ith CKD are strikin'& (#ter ad7$st!ent #or
a'e, 'ender, race, co!or-idity, and prior hospitali8ations, !ortality in
patients "ith CKD in 2009 "as 35G 'reater than that in patients "itho$t
CKD&
1232
<or patients "ith sta'es 4*3 CKD, the ad7$sted !ortality rate is @5G
'reater&
)ortality rates are consistently hi'her #or !en than #or "o!en, and #or
-lack persons than #or "hite indi%id$als and patients o# other races& <or
)edicare CKD patients a'ed 55 years and older, deaths per 1000 patient*
years in 2009 "ere @3 #or "hite patients and 46 #or -lack patients&
1232
,he hi'hest !ortality rate is "ithin the #irst 5 !onths o# initiatin' dialysis&
)ortality then tends to i!pro%e o%er the ne.t 5 !onths, -e#ore increasin'
'rad$ally o%er the ne.t 4 years& ,he 3*year s$r%i%al rate #or a patient
$nder'oin' lon'*ter! dialysis in the United States is appro.i!ately 63G,
and appro.i!ately 23G in patients "ith dia-etes&
( st$dy -y Sens #o$nd that the risk o# !ortality "as ele%ated in patients
"ith ES:D and con'esti%e heart #ail$re "ho recei%ed peritoneal dialysis
co!pared "ith those "ho recei%ed he!odialysis&
1602
)edian s$r%i%al ti!e
"as 20&4 !onths in patients recei%in' peritoneal dialysis %ers$s 65&@
!onths in the he!odialysis 'ro$p&
(t e%ery a'e, patients "ith ES:D on dialysis ha%e si'ni#icantly increased
!ortality "hen co!pared "ith nondialysis patients and indi%id$als "itho$t
kidney disease& (t a'e 50 years, a healthy person can e.pect to li%e #or
!ore than 20 years, "hereas the li#e e.pectancy o# a patient a'ed 50 years
"ho is startin' he!odialysis is closer to 4 years& (!on' patients a'ed 53
years or older "ho ha%e ES:D, !ortality rates are 5 ti!es hi'her than in
the 'eneral pop$lation&
1232
,he !ost co!!on ca$se o# s$dden death in patients "ith ES:D is
hyperkale!ia, "hich o#ten #ollo"s !issed dialysis or dietary indiscretion&
,he !ost co!!on ca$se o# death o%erall in the dialysis pop$lation is
cardio%asc$lar diseaseF cardio%asc$lar !ortality is 10*20 ti!es hi'her in
dialysis patients than in the 'eneral pop$lation&
1612
,he !or-idity and !ortality o# dialysis patients is !$ch hi'her in the United
States than in !ost other co$ntries, "hich is pro-a-ly a conseC$ence o#
selection -ias& /eca$se o# li-eral criteria #or recei%in' 'o%ern!ent*#$nded
dialysis in the United States and the $se o# rationin' (!edical and
econo!ic in !ost other co$ntries, US patients recei%in' dialysis are on the
a%era'e older and sicker than those in other co$ntries&
+n the Dational 9ealth and D$trition E.a!ination S$r%ey (D9(DES +++
pre%alence st$dy, hypoal-$!ine!ia (a !arker o# protein*ener'y
!aln$trition and a po"er#$l predicti%e !arker o# !ortality in dialysis
patients, as "ell as in the 'eneral pop$lation "as independently
associated "ith lo" -icar-onate, as "ell as "ith the in#la!!atory !arker
C*reacti%e protein& ( st$dy -y :aphael et al s$''ests that hi'her ser$!
-icar-onate le%els are associated "ith -etter s$r%i%al and renal o$tco!es
in (#rican (!ericans&
1622
( st$dy -y Da%aneethan et al #o$nd a connection -et"een lo" le%els o# 23*
hydro.y%ita!in D (231E92D and all*ca$se !ortality in patients "ith
nondialysis CKD&
1662
(d7$sted risk o# !ortality "as 66G hi'her in patients
"hose 23(E9D le%els "ere -elo" 13 n'?!>&
)or-idity and !ortality a!on' children "ith CKD and ES:D are !$ch
lo"er than a!on' ad$lts "ith these conditions, -$t they are strikin'ly
hi'her than #or healthy children& (s "ith ad$lts, the risk is hi'hest a!on'
dialysis patientsF conseC$ently, transplantation is the pre#erred treat!ent
#or pediatric patients "ith ES:D&
Se(ual and reproducti*e issues
P$-erty is o#ten delayed a!on' !ales and #e!ales "ith si'ni#icant CKD&
<e!ale patients "ith ad%anced CKD co!!only de%elop !enstr$al
irre'$larities& Ho!en "ith ES:D are typically a!enorrheic and in#ertile&
9o"e%er, pre'nancy can occ$r and can -e associated "ith accelerated
renal decline, incl$din' in "o!en "ith a kidney transplant& +n ad%anced
CKD and ES:D, pre'nancy is associated "ith !arkedly decreased #etal
s$r%i%al&
Vitamin D
)any patients "ith CKD ha%e lo" circ$latin' le%els o# 23(E9D& ( st$dy o#
1099 patients (!ostly !en "ith ad%anced CKD #o$nd that the lo"est tertile
o# 1,23(E9(2D (B 13 p'?!> "as associated "ith death and initiation o#
lon'*ter! dialysis therapy co!pared "ith the hi'hest tertile (=22 p'?!>&
1642
( retrospecti%e cohort st$dy in 12,@56 nonIdialysis*dependent patients
"ith CKD #o$nd that 23(E9D le%els -elo" 13 n'?!> "ere associated
independently "ith all*ca$se !ortality&
1632
Patient Ed$cation
Patients "ith chronic kidney disease (CKD sho$ld -e ed$cated a-o$t the
#ollo"in':
+!portance o# a%oidin' #actors leadin' to increased pro'ression (see
Etiolo'y
Dat$ral disease pro'ression
Prescri-ed !edications (hi'hli'htin' their potential -ene#its and
ad%erse e##ects
(%oidance o# nephroto.ins
Diet (see Diet
:enal replace!ent !odalities, incl$din' peritoneal dialysis,
he!odialysis, and transplantation
,i!ely place!ent o# %asc$lar access #or he!odialysis
Ho!en o# child-earin' a'e "ho ha%e end*sta'e renal disease (ES:D
sho$ld -e co$nseled that altho$'h their #ertility is 'reatly red$ced,
pre'nancy can occ$r and is associated "ith hi'her risk than in "o!en "ho
do not ha%e renal disease& +n addition, !any !edications $sed to treat
CKD are potentially terato'enicF in partic$lar, "o!en takin' an'iotensin*
con%ertin' en8y!e ((CE inhi-itors and certain i!!$nos$ppressi%e
treat!ents reC$ire clear co$nselin'&