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Uremic Syndrome
Acute Kidney Injury Chronic Kidney Disease
Lecture 3: Genito-urinary system.
10 – 08 – 2009.
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Uremic Syndrome
Acute Kidney Injury Chronic Kidney Disease
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nephron
the functional unit of the kidney
•capable of forming urine
•has two major components:
glomerulus
tubule:proximalloop of Henledistal
collecting
Interstitium
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renal parenchymacortex
medulla
nephronscortical
juxtamedullary
structural organization
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Renal Function:
Excretory
Regulatory
Endocrine
Excretory Function:
Glomerular
Glomerular Filtration Rate GFR! Creatinin Clearance"
Ux#$% ml$min
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GFR:
inulin clearance
EDTA isotop
99 Tc isotop Iohexal High Performance
liquid chromatography
Clinical setting: e!": Coc#roft$ault !ormula
%D"D !ormula
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Coc#roft$ault !ormula
%ale: &'() x *&+, - age . x /0 *#g. Ccr 1 $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ ml2min
3cr *4 mol2min.
5r &+, - age *yrs. x /0 *#g. Ccr 1 $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ ml2min
6(x 3cr *mg2dl.
!emale: &+, - age *yrs. x /0 *#g.
Ccr 1 $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ ml2min 6, x 3cr *mg2dl.
5r Ccr* male. x o787
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NKF-KDO! recommen"ationNKF-KDO! recommen"ation
AdultsCockcroft-Gault equation:
GFR (ml/min) = (140-ae) ! "ei#t /$% & 'cr !(0* if female)
+,R, (modification of diet in renal disease) equation:
GFR (ml/min/1$ m%) = 1. ! ('Cr) -11*4 ! (Ae) -0%0 !
(0$4% if female) ! (1%10 if lack)
C#ildren'c#art equation: GFR (ml/min) = 0** & lent#/'cr
Couna#an-2arratt equation: GFR (ml/min/1$m%)= 04 ! 3ent#/'cr
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Renal Function:
Excretory
Regulatory
Endocrine
Regulatory Function:
&u'ulo(interstitial
) *ater and electrolyte 'alance) acid('ase 'alance
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Renal Function:
Excretory
Regulatory
Endocrine
Endocrine Function:
renal +arenchymal
renin, +rostaglandin,erythro+oietin, calcitriol
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#remic $o%icity#remic $o%icity
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#remia-1#remia-1
Gree- *ords : urine . 'lood / uremia
Uremia is the retention o0 excessi1e 'y
+roducts o0 +rotein meta'olism in the 'lood
and the toxic condition +roduced there'y"
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#remia-2#remia-2
Uremia is a toxic syndrome caused 'y se1ere
glomerular insu00iciency, associated *ith
distur'ances in tu'ular and endocrine 0unctions o0the -idney"
It is characteri2ed 'y retention o0 toxic
meta'olites, associated *ith changes in 1olume
and electrolyte com+osition o0 the 'ody 0luids andexcess or de0iciency o0 1arious hormones uremic
syndrome!"
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$o%ic e&&ects o& uremic '(asma$o%ic e&&ects o& uremic '(asma
1ariety distur'ances:
anemia, immunologic de0iciency,
'leeding tendency, disorders o0
car'ohydrate and li+id meta'olism,
and 1arious mem'rane trans+ortdistur'ances"
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#remia#remia
General 3 Fatigue, *ea-ness
3 %ruritus
4ental$neurologic status change 3 Uremic ence+halo+athy
3 Sei2ures
3 Asterixis
GI distur'ance 3 Anorexia, early satiety, 5$#,
remic 5ericarditisremic 5ericarditis
%latelet dys0unction$'leeding
An excess in the 'lood o0 urea, creatinine and other
nitrogenous end +roducts *ith signs and sym+toms listed "
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#remic to%ins#remic to%ins
)ma((* mi""(e-si+e"* an" (ar,e mo(ecu(es)ma((* mi""(e-si+e"* an" (ar,e mo(ecu(es
Si2e: Small : 6 788 or 978 ! Da
4iddle : 788 7,888 Da
;arge : < 7,888 Da
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$o%icity o& inor,anic sustances$o%icity o& inor,anic sustances
in uremiain uremia=ater
Sodium
%otassium>ydrogen ions
4agnesium
%hos+hate
Sul0ate
&race elements
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Or,anic com'oun"s o& LoOr,anic com'oun"s o& Lo
mo(ecu(ar ei,/tmo(ecu(ar ei,/tUrea
Creatinine
Guanidines other than creatinine!4ethylguanidine
Guanidinosuccinic Acid GSA!
4ethylated Arginine 4eta'olites?ther guanidines
%roducts o0 5ucleic Acid 4eta'olism
O i " & L ( ( i /t
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#rea 1#rea 1
&he most im+ortant end +roduct o0 nitrogen
meta'olism in mammals and account 0or
@7 o0 the urinary nitrogen excretion"Blood concentration: glomerular 0iltration
rate, nitrogen inta-e, 'alance 'et*een
endogenous +rotein synthesis and 'rea-do*n"
Or,anic com'oun"s o& Lo mo(ecu(ar ei,/t
O i " & L ( ( i /t
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#rea3#rea3
>igh concentration: headache, 0atigue,
nausea, 1omiting, glucose intolerance, and
'leeding"&he most se1ere uremic GI, C#, mental and
neurologic changes *ere not seen"
Considered mild uremic toxin "
Role in the +atho+hysiology o0 uremia is not
*ell de0ined"
Or,anic com'oun"s o& Lo mo(ecu(ar ei,/t
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)erum reatinine)erum reatinine
Serum creatinine is a re0lection o0 creatinineclearance
Creatinine +roduction is determined 'y muscle massand must 'e inter+reted *ith res+ect to +ts age,*eight and sex"
Creatinine is 0iltered and secreted and tends to o1erestimate GFR"
Certain diseases and medications inter0ere *ithcorrelation 'et*een serum Cr and GFR" i"e"" Acuteglomerulone+hritis, trimetho+rim, cimetidine!
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)erum reatinine cont.)erum reatinine cont.
5one o0 the euations accurately determine
GFR in ARF" Assume Cr is sta'le!
4ore accurate techniues in1ol1e nuclear
medicine studies and GFR scans"
5e* 'iochemical mar-ers in1estigated i"e""
Cystatin C!
Or,anic com'oun"s o& Lo mo(ecu(ar ei,/t
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Ot/er ,uani"inesOt/er ,uani"ines
&he concentrations o0 1arious guanidinecom+ounds are higher in uremic +atients"
Some toxic in 1itro e00ects seem to ha1e 'eeno'tained at concentrations similar to those inuremic 'ody 0luids"
4ost in 1itro and in 1i1o toxic e00ects ha1e 'eeno'ser1ed at much higher concentrations than are
0ound in uremic +atients&he role o0 guanidines as uremic toxins is still not
*ell de0ined"
Or,anic com'oun"s o& Lo mo(ecu(ar ei,/t
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ro"uct o& Nuc(eic 4ci"ro"uct o& Nuc(eic 4ci"
5etao(ism5etao(ism Uric acid and other +urine deri1ati1es
Cyclic A4%
%yridine deri1ati1es
Amino acids, di+e+tides, and tri+e+tides Sul0ur amino acids
Ali+hatic amines
Aromatic amines
%olyamines Indoles
%henols
Car'onhyrate deri1ati1es
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5i""(e mo(ecu(es as uremic5i""(e mo(ecu(es as uremic
to%insto%ins&he middle molecule hy+othesis:
%eritoneal mem'rane *as more lea-y and thus
more e00ecti1e at remo1ing middle molecules thanthe hemodialysis mem'ranes"
It is *ell esta'lished that CA%D +atients may
sur1i1e and thri1e as *ell as >D +atients do, e1en
though their a1erage *ee-ly clearance o0 urea is
considera'ly lo*er than that 0or >D +atients"
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$o%ic e&&ects o& cru"e 55$o%ic e&&ects o& cru"e 55
&ractions&ractions Inhi'ition o0 +roli0eration o0 undi00erentiated cell
lines and hemato+oietic cell lines, de+ression o0
se1eral immmune 0unction, increase hemolysis,cardiotoxicity, inhi'ition o0 +latelet aggregation,
inhi'ition o0 glucose utili2ation, inhi'it +rotein
synthesis and amino acid trans+ort, inhi'ition o0
mitochondrial res+iration Inhi'it osteoclast mitogenesis
Some en2yme acti1ities are also inhi'ited
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arat/yroi" /ormonearat/yroi" /ormone
Incresed in uremic +atients as conseuence o0
+hos+hate retention, decreasing ioni2ed calcium
stimulate +arathyroid glands to increase %&>secretion
%&> hy+ersecretio+n in uremic +atients :
ence+halo+athy, neuro+athy, dementia, 'one
disease, so0t tissue calci0ication, hy+ertension,cardiomegaly, car'ohydrate intolerance, anemia,
sextual dys0unction
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6i,/-mo(ecu(ar-ei,/t 'e'ti"es6i,/-mo(ecu(ar-ei,/t 'e'ti"es
an" 'roteinsan" 'roteinsRi'onuclease
Granulocyte(inhi'iting +roteins
Com+lement 0actors
Beta(4icroglo'ulin and Dialysis(related
amyloidosis
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#remic )yn"rome#remic )yn"rome
4cute Ki"ney !n7ury 4cute Ki"ney !n7ury /ronic Ki"ney Disease/ronic Ki"ney Disease
Lecture 3: Genito-urinary system.
10 – 08 – 2009.
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acute kidney injury: definition
ARF is an abrupt decline in glomerular andtubular function, resulting in the failure of the
kidneys to excrete nitrogenous waste productsand to maintain fluid and electrolytehomeostasis
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'i"emio(o,y'i"emio(o,y
7 o0 hos+itali2ed +atients de1" ARF"
8"7 o0 these +atients reuire dialysis"
8 o0 critical care admissions de1" ARF"
>os+ital acuired ARF usually de1elo+s in
the setting o0 ICU secondary to multisystem
organ 0ailure"
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R!FL (assi&icationR!FL (assi&ication
%004 A,67 rou8 classification
Ris- R! (Increase Cr xH"7 or Decrease GFR x 7 or U?68"7 ml$-g$hr x hrs
Injury I!( Increase Cr x"8 or Decrease GFR x 78 or U?68"7 ml$-g$hr x Hhrs
Failure F!( Increase Cr x9"8 or Decrease GFR xJ7 oranuria x H hours
;oss ;!( %ersistent ARF, com+lete loss o0 -idney 0unction
x *ee-s needing RR&!End Stage Kidney Disease E!( ;oss o0 -idney 0unction x 9
months
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The Second International Consensus Conference of
the Acute Dialysis Quality Initiative (ADQI) Group
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A K I
PRE RENAL RENAL POST RENAL
Loss of intra-vas. vol
Reduced cardiac-output Periferal #asodilatation
Increased reno-vasc resistenceReduced intra-glomerular pressure
ACE-i
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;oss o0 intra(1asc 1ol"" Reduced cardiac(out+ut B;EEDI5G C>F
%?;LURIA, SA;&(;??SI5G G5 CARDI?GE5IC S>?CK
G(I &RAC& F;UIG ;?SS %ERICARDIA;$&A4%?5ADE
%R?FUSE S=EA&I5G 4ASSI#E ;U5G E4B?;I
&ISSUE &AU4A E&C
%eri0er #asodilatation Increase reno(1asc"resistence
SE%SIS SURGERL
A5&I(>I%ER&E5SI#E DRUGS A5ES&EL>ICS
A5A%>L;AMIS >E%A&?RE5A; SL5DR
#AS?C?5S&RIC& DRUGS
Reduced intraglom" +ressure ACE(i
ACU&E KID5EL I5NURL
%re(renal
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A K I
PRERENAL RENAL POST RENAL
I! "ESSELS
S#ALL "ESSELS!LO#ER$LARINTERSTITI$#
T$$LAR
BIG VSS!S S"A!! VSS!S
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BIG VSS!S S"A!! VSS!S
STENOSIS A.RENALIS VASCULITIS, ATHEROEMBOLIC
DIS. THROMBOSIS/EMBOLI THROMBOTIC
MICROANGIOPATHY
G!#"$%!A$& I'T$STITI%" Ix deposit !o". Dise#se A$%te i&te'stiti#!&ep('itis
ps&, !%p%s &ep('itis, MPGN et$ AB, Di%'eti$s,NSAID,
RPGN #!!op%'i&o! d!! Goodp#st%'e s)&d'
No& Ix deposit *ee&e'+s '#&%!o"#tosis, Po!)#'te'iitis
&odos#, Idiop. C'es$.GN
T%B%!A$&
Re&#! is$(e"i# s(o$-, !eedi&, t'#%"#, '#" 01 #$te'i#,
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A K I
PRERENAL RENAL POST RENAL
Stone% Cr&stals Prostate% $reteric
Stricture 'ilateral or uni-lateral in singlefunctioning (idne&
#E)ICAL S$R!ICAL
auses o& 4RF in 6os'ita(i+e"auses o& 4RF in 6os'ita(i+e"
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auses o& 4RF in 6os'ita(i+e"auses o& 4RF in 6os'ita(i+e"
atientsatients4*9 A;
7sc#emia< ;e8#roto&ins
%19 5rerenal CF< >olume de8letion< se8sis
109 rinar? ostruction
49 Glomerulone8#ritis or >asculitis
%9 Acute 7nterstitial ;e8#ritis
19 At#eroemoli
etc
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re Rena( 4+otemiare Rena( 4+otemia
Im+aired renal 'lood 0lo* as a result o0 trueintra1ascular de+letion, decreased e00ecti1ecirculating 1olume to the -idneys, or agents that
im+air renal 'lood 0lo*"Urine and 'lood studies are hel+0ul in diagnosing
+re renal ARF"
>yaline casts can 'e seen 5ot an a'normal0inding!"
&reat *ith 0luid 'oluses or continuous I#F, monitorurine out+ut"
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ost Ostructie #ro'at/yost Ostructie #ro'at/y
?ccurs i0 'oth urinary out0lo* tracts are o'structed orout0lo* tract o0 solitary -idney is o'structed"
%atients *ith SUDDE5 ?5SE& o0 anuria are li-ely toha1e +ost o'structi1e uro+athy"
%rimary causes include B%>, +rostate and cer1ical cancer,stones, strictures and retro+eritoneal 0i'rosis"
Bladder catheteri2ation and Renal U$S to assesshydrone+hrosis"
Can ha1e o'struction *$o hydrone+hrosis on U$S
4onitor 0or +ost o'structi1e diuresis, hemorrhagic cystitisO
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!ntrinsic 4cute Ki"ney !n7ury!ntrinsic 4cute Ki"ney !n7ury
H" &u'ular A&5!
" Interstitial AI5!
9" Glomerular Glomerulone+hritis!
" #ascular
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4$N 4$N
4ost common cause o0 ARF in hos+itali2ed +atientsContrast and aminoglycosides most o0ten associated *ith
nonischemic A&5"
9 +hases:
H! Initiation +hase( Renal injury lasting hours to days"! 4aintenance +hase( ;asts days to *ee-s" GFR andU"? at lo*est"
9! Reco1ery %hase( %ostacute tu'ular necrosis diuresis"Can still ex+" uremia and hy+o1olemia as tu'ular 0unction
not com+letely restored"
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4cute !nterstitia( Ne'/ritis 4cute !nterstitia( Ne'/ritis
J8 Drug hy+ersensiti1ity 98 Anti'iotics: %C5s 4ethicillin!, Ce+halos+orins, Ci+ro Sul0a drugs 5SAIDs Allo+urinol"""
H7 In0ection Stre+, ;egionella, C4#, other 'act$1iruses
@ Idio+athic
Autoimmune D2 Sarcoid, &u'ulointerstitial ne+hritis$U1eitis!
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4!N &rom Dru,s 4!N &rom Dru,s
Renal damage is 5?& dose(de+endent
4ay ta-e *-s a0ter initial ex+osure to drug U+ to H@ mos to get AI5 0rom 5SAIDSP
But only 9(7 d to de1elo+ AI5 a0ter second ex+osure to drug
Fe1er J! Serum Eosino+hilia 9! 4aculo+a+ular rash H7!
Bland sediment or =BCs, sterile +yuria most commonly seen =BC Casts are common
Urine eosino+hils on =rights or >ansels Stain( Also see urine eos in R%G5, renal atheroem'oli"""
&reatment is to remo1e o00ending agents" 4ost +atients reco1er com+lete -idney0unction *$I one year"
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Ne'/ritic )yn"romesNe'/ritic )yn"romes&y+e H: Anti(GB4 d2 Anti GB4 A' +ositi1e!( Good+astures Disease( Anti(GB4
&y+e : Immune com+lex ;o* com+liment, ele1ated ESR! IgA ne+hro+athy 5ormal Com+liment le1els! %ostin0ectious glomerulone+hritis ;u+us ne+hritis 4ixed cryoglo'ulinemia 4%G5 IBE
&y+e 9: %auci(immune A5CA +ositi1e, assoc *ith 1asculitis! =egners Disease 4icrosco+ic %olyangitis Churg(Strauss
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Ne'/ritic )yn"romesNe'/ritic )yn"romes
Fe1er
?liguria
>ematuria>tn
RBC casts
%roteinuria H(grams usually!&reatment 1aries 'ased on underlying disease
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Rena( 4t/eroemo(ic D%Rena( 4t/eroemo(ic D%
H o0 Cardiac caths: atheromatous de'ris scra+ed 0rom theaortic *all *ill em'oli2e
3 Retinal
3 Cere'ral 3 S-in ;i1edo Reticularis, %ur+le toes!
3 Renal ARF!
3 Gut 4esenteric ischemia!
Cr *ill 5?& im+ro1e *ith I#F Diagnosis o0 exclusion: *ill 5?& sho* u+ on 4RI or Renal
U$SQ =I;; sho* u+ on renal 'x
&x: su++orti1e
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acute rena( &ai(ure:acute rena( &ai(ure: 'reention'reention
recogni2e +atients at ris- +osto+erati1e states, cardiac
surgery, se+tic shoc-!
+re1ent +rogression 0rom +rerenal to renal
+reser1e renal +er0usion 3 iso1olemia, cardiac out+ut, normal 'lood +ressure
3 a1oid ne+hrotoxins aminoglycosides, 5SAIDS, am+hotericin!
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$reatment$reatment
Re1erse underlying causes and correct 0luid
and electrolyte 'alances
&reatment is su++orti1e"Drugs such as mannitol, loo+ diuretics,
do+amine and CCB success0ul in +romoting
diuresis in animals 'ut not in humans"Dialysis as needed I>D 1s" CRR&!
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acute rena( &ai(ure:acute rena( &ai(ure: mana,ementmana,ement
treat the underlying diseases
strictly monitor inta-e and out+ut *eight, urine out+ut,
insensi'le losses, I#F!monitor serum electrolytes
adjust medication dosages according to GFR
a1oid highly ne+hrotoxic drugs
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nutritionnutrition
8ro>ide adequate caloric intake
limit +rotein inta-e to control increases in BU5
minimi2e +otassium and +hos+horus inta-e
;imit 5a$0luid inta-e
If adequate caloric intake can not be achieved
due to fluid limitations, some form of dialysisshould be considered
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acute rena( &ai(ure:acute rena( &ai(ure: &(ui" t/era'y&(ui" t/era'y7f 8atient is fluid o>erloaded
0luid restriction insensi'le *ater losses!
attem+t 0urosemide H( mg$-g not e1idence('ased!
Renal re+lacement$su++ort thera+y see later!
7f 8atient is de#?drated: restore intra1ascular 1olume 0irst
then treat as eu1olemic 'elo*!
7f 8atient is eu>olemic: restrict to insensi'le losses 98(97 ml$H88-cal$ hours! .
other losses urine, chest tu'es, etc!
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Daily fluid alloance:Daily fluid alloance:
A;;50A<CEA;;50A<CE 1 =olume Excreted > I 0 ;1 =olume Excreted > I 0 ;
(+ hrs(+ hrs
=olume Excreted :=olume Excreted : ?rine' @omitus' diarhea'?rine' @omitus' diarhea'
drain' etcdrain' etc
I 0 ; :I 0 ; : ,, ml 2 (+ hrs,, ml 2 (+ hrs , #g /0 T )6, #g /0 T )6 ,,CC & B & B increment of &increment of & ,,CC
%onitor daily /0 %onitor daily /0
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so"iumso"ium
most +atients ha1e dilutional hy+onatremia *hich
should 'e treated *ith 0luid restriction
se1ere hy+onatremia 5a6 H7 mE$;! or
hy+ernatremia 5a< H78 mE$;!: dialysis or
hemo0iltration
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$reatment o& 6y'era(emia$reatment o& 6y'era(emia
Calcium Gluconate
Glucose and InsulinSodium Bicar'onate
Diuretics ;asix!
Cation(exchange resins Kayexalate!Dialysis
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4cute !n"ications &or Dia(ysis 4cute !n"ications &or Dia(ysis
AIUE?Acidosis meta'olic!
Ingestion o0 drugs$Ischemia
Uremic syndrome
Electrolytes hy+er-alemia!?1erload 0luid!
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"A'AG"'TA K I
*L$I)
)IET
)R$!
RRT+S$PPORT
Severe uremic s&mptoms $rea , mg/%Cr ,0 mg/ 1 , 2 mg/ Pericarditis Severe Asidosis
Pulmonar& Oedema
)IAL3SIS
PERITONEAL 4E#O
INDIKASI :
"#I!T$ATI#'
CA"4 5d6% C""4 5d6
SC% (d)* S!DD
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5orta(ity;5ori"ity5orta(ity;5ori"ity
4ortality rates range 0rom J(@8 de+ending on +atients other co mor'idities"
&his rate has remained unchanged since the ad1ento0 dialysis 'ecause o0 increasing age and comor'id conditions"
4ost common cause o0 death associated *ith ARF
are se+sis, cardiac 0ailure and res+iratory 0ailure"4ortality rates are lo*er 0or nonoliguric
<88ml$day! then oliguric ARF 688 ml$day!"
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Take Home PointsTake Home Points
Features of the history and physical examination
in addition to relevant lab and radiologic
investigations help to determine the most likelycause(s) of ARF in a given patient
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Take Home PointsTake Home Points
anagement of a patient !ith ARF involves"
# Treating potentially life$threatening complications
# Reversing pre$renal and post$renal causes# inimi%ing further hemodynamic and toxic insults to
the kidney
# Admission and appropriate consultation# &ack of evidence for converting oliguric to non$
oliguric ARF
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#remic )yn"rome#remic )yn"rome
4cute Ki"ney !n7ury 4cute Ki"ney !n7ury /ronic Ki"ney Disease/ronic Ki"ney Disease
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CKD
PARENC43#AL OSTR$CTI"E
G' Dia+etic 'ephropathy 'ephrosclerotic,hypertension
Polic&stic Lupus TC
urolit7iasis Prostate
$reteric Stricture
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De&inition o& De&inition o&
/ronic Ki"ney Disease/ronic Ki"ney Disease
4<KD 2002: 392
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NKF-KDO! recommen"ationNKF-KDO! recommen"ation
Adults
+,R, (modification of diet in renal disease) equation:
GFR (ml/min/1$ m%) = 1. ! ('Cr) -11*4 ! (Ae) -0%0 !
(0$4% if female) ! (1%10 if lack)
C#ildren
'c#art equation: GFR (ml/min) = 0** & lent#/'cr
Couna#an-2arratt equation: GFR (ml/min/1$m%)= 04 !3ent#/'cr
iota( Rote o& G(omeru(ar 6y'ertensioniota( Rote o& G(omeru(ar 6y'ertensionin t/ein t/e !nitiation!nitiation an"an" ro,ressionro,ression
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in t/ein t/e !nitiation!nitiation an"an" ro,ressionro,ression
o& )tructura( !n7uryo& )tructura( !n7ury..
4n"erson ). =renner. < 5e" 1989 > ?0 : 18@-189.
)ystemic
6y'ertension
4,in,* Diaetes
5e(itus* Dietary
Factors
E<D5THE;IA; I<?"
Re(ease o& asoactie
&actors
Aascu(ar (i'i" "e'osition
!ntraca'i((ary t/romosis
%E3A<IA; I<?"
4ccumu(ation o& macromo(ecu(es↑5atri% 'ro"uction
↑ e(( 'ro(i&eration
EPITHE;IA; I<?"
Proteinuria
↓ ermeai(ity to ater
GLO5R#L4R 6BR$N)!ON
GLO5R#L4R )LRO)!)
rimary Rena(
Disease Rena(
4(ation
5 i i
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5rotein leakae
5roteinuria
5rotein load to5ro&imal tuules
Gene e&8ression
for inflamationransdifferentiation
to m?ofilolast
Glomerular ?8ertension Firosis
An 77 GF @ 1< etc
5roliferation?8ertension
+atri& s?nt#esis
%R?GRESSI?5 o0 CKD
Interstitium
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kno?an G< A'; '?m8<5#iladel8#ia<%00%
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KD re"icts ADKD re"icts AD
Go* et a(.* 200C
4 , e - )
t a n " a r " i + e " R a t e
o & 2 a r " i o 9 a s c u ( a r
8 9 e n t s ' e r 1 0 0
' e r s o n - y r
stimate" GFR mL;min;1.?3 m2
)ta,e@ N 3?2 0003tage and
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)ta,e 1
)ta,e 2
)ta,e 3
)ta,e C
)ta,e@
N@*900*000
GFRE90
N@*300*000
GFR 0-89
N?*00*00
GFR 30-@9
GFR 1@-29
GFR H1@
N3?2*000
NC00*000
!" measurement in m;2min2&76) m(
3tage and
pre@alence of CFD
in indi@iduals older
than (, years
J
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.
6eert et aL: K! 2001 @9:1211-2
E S R D
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In normal healthy indi1iduals, the eGFR *ill 0all
'y u+ to H8 ml$min ie H8! +er decade
An @8 year old man *ill ha1e an e&8ected eGFR o0
78(8 ml$min
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"I3F !ACT5"3 !5" CFD
P"5"E33I5<
GN$!
HPE";CE%IA
R44) 4$!A!$B
HPE"TE<3I5<
P"5TEI<?"IA
6BRL!!D5!4
CIA"ETTE3
6O5OB)$!N
3A;T I<TAFE
P"5TEI< I<TAFE
GNDR
A<E%IA
6BOK4L5!4
6BR6O)64$5!
NDOGNO#)
!N)#L!N I))
6eert et aL: K! 2001 @9:1211-2
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ar"ioascu(ar "isease in KD
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Damage to the heart
*?raemic cardiomyopathy)
Damage to the arteries
*?raemic arteriopathy.
h di h
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chocardio-raphy
Startin- DialysisTherapy
Ki"ney !nt 199@
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omori"ities in KDomori"ities in KD
./
-./
8./
9./
0./
:../
All cardiovascular
disease
)ia'etes Isc7aemic 7eart
disease
4eart failure Perip7eral vascular
disease
4&pertension
No C1)
Stage ; C1)
Stage 8 C1)
Stage < C1)
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GFR mL;min;1*?3 m2
JOri,ina( stu"y 'er&ormance usin, /ematocrit
&rom Ra"te et e(* =(oo" 19?9>@C:8??-88C.
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CA"DIAC "E%5DE;;I< "E3?;TI< !"5%
A<E%IA A<D HPE"TE<3I5<
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A<E%IA A<D HPE"TE<3I5<
CFD
C5<CE<T"IC
;=H
DI;ATED ;=H
0ITH HEA"T
!AI;?"E
ECCE<T"IC
;=H
6 B 3 8
R $ 8 N
) ! O N
4 n e m i a
LADA :H90 m(;m2
Norma( LA5 :12 ,;m2
LADA :H90 m(;m2
LA6 (e&t enticu(er /y'ertro'/y> LA5LA mass> LADALA en" "iasto(ic o(ume
Lo'e+-Gome+ et a(.Ki"ney !nt.1998>@C:992-)=> Lon"on et a(. 4" Ren Re'(ace
$/er. 199?>C:19C-211. ase(e et a(.4nn !ntern 5e"icine.198>10:1?3-1?
Anemia associated it# increased risk of stroke
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7n CB, 8atients/
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kno?an G< A'; '?m8<5#iladel8#ia<%00%
a(citrio( Dec(ine an" i$6 (eationa(citrio( Dec(ine an" i$6 (eation
KD KD
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as KD ro,ressesas KD ro,resses
< 1 &,7
iPTH 1 intact PTH7Adapted from %artineG et al7 Nephrol Dial Transplant. &99&&*suppl ).:(($(87
e!" *m;2min2&76) m(.
&()+689&,
&,,
(,,
),,
+,,
,
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(,
),
+,
,
i P T H
* p g 2 m ; .
C
a l c i t r i o l
& ' ( 9 * 5 H . ( D ) * p g 2 m ; .
3tage )
67+ million
3tage (
76 million
3tage +
),,',,,
CFD 3tage &
7 million
(
;o$<ormal
Calcitriol
High$<ormal
PTH
J (,, The ohns Hop#ins ?ni@ersity 3chool of %edicine7
)ysto(ic =(oo" ressure an")ysto(ic =(oo" ressure an"
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ro,ression o& KDro,ression o& KD
4!RD )tu"y Grou' 4!RD )tu"y Grou'5eta-ana(ysis o& 11 R$s o& 4!s
@@9 recor"s it/ non-"iaetic i"ney "isease
RR
)ysto(ic = mm6,
<a&ar et a(* 4nn !ntern 5e" 2003>139:2CC-2@2
#rine rotein %cretion an"#rine rotein %cretion an"ro,ression o& KDro,ression o& KD
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ro,ression o& KDro,ression o& KD
4!RD )tu"y Grou' 4!RD )tu"y Grou'
5eta-ana(ysis o& 11 R$s o& 4!s
C8@ recor"s it/ non-"iaetic i"ney "isease
RR
#rine 'rotein e%cretion ,;"ay
<a&ar et a(* 4nn !ntern 5e" 2003>139:2CC-2@2
)yner,istic e&&ect o& KD*6F an")yner,istic e&&ect o& KD*6F an"
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y , *y ,
4nemia as ris &actors &or Deat/ 4nemia as ris &actors &or Deat/
'ollins Adv studies in ed **+
yr mortality (n, ***** -. edicare sample)
.
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kno?an G< A'; '?m8<5#iladel8#ia<%00%
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/o are at ris/o are at ris
&hose *ho are hy+ertensi1e, dia'etic, o'ese,
renal stone"
&hose *ith 0amily history o0:
hy+ertension, dia'etes, and renal disease$
0ailure
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'c#oolert# A A;;A +eetin %00%
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Acute onChronic
Infection + $TI
)e7&dration
O'structive
Electrol&te )istur'.
Severe 4&pertension
C K D
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C K D
STA!E : STA!E STA!E ;-8 STA!E <
Decre.entof recidualrenal function
$enalinsu/ciency
$enal failureS$D
ris- ris-
ris-
&x
&x &x
Decisions in rena(Decisions in rena(
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Decisions in rena(Decisions in rena(
re'(acementre'(acement
%re(dialysis care
Acti1e treatment
( %eritoneal dialysis %D!
( >aemodialysis >D!
( &rans+lantation
Conser1ati1e non(dialytic! care" Sym+tom
management"
M =(oo" 'ressure an" 'roteinuria contro(
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M orrection o& /y'er,(ycaemia
M Dietary mana,ement
M orrection o& ca(cium-'/os'/ate
"isor"ers
M orrection o& /y'er(i'i"aemia
M orrection o& anemia an" aci"osis
M essation o& smoin,
M t/e im'ortance o& ear(y re&erra( to a
ne'/ro(o,ist
Decisions in rena(Decisions in rena(
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Decisions in rena(Decisions in rena(
re'(acementre'(acement
%re(dialysis care
&reat: hy+ertension
hy+erglycemiahy+erli+idemia
anemia
&o target
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Diet: ;o* %rotein
Anti RAAS antihy+ertensi1es
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3mo#ing and progression
rel7 ris# @s7non$smo#ers
smo#ers'
no ACE inhiKitors &, ,7,,&
smo#ers
treated ith ACE inhiKitors &7) <737
Orth, Kidn Intern (1998)Orth, Kidn Intern (1998) 5454: 926 : 926
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4m < Ki"ney Dis 2002 39:3?-82
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4m < Ki"ney Dis 2002 39:3?-82
ns
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ontro( %ercise
= =F F = =F F
= F = F
= F = F
ontro( %ercise
ontro(
ontro( %ercise
%ercise
ns0.0C 0.00? 0.03
[email protected]@ nsns
ontro( ontro(%ercise %ercise
F FFF= = = =
5enaru# reular mild aquatic e&ercise selama ulan
=
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Kidney International Vol 66 (2004), pp: 753-760
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Ki"ney !nt 200C : ?@3 - 0
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Ki"ney !nt 200C : ?@3 - 0
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Ki"ney !nt 200C : ?@3 - 0
Early Treatment %a#es a DifferenceEarly Treatment %a#es a Difference
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Early Treatment %a#es a DifferenceEarly Treatment %a#es a Difference
"A'AG"'T
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CKD
C#'S$VATIV $$T
)iet = >ater ? saltProteinCalori
P7osp7ate% 1?
Ris(-factors management
S&mptomatic #edicament =
"A'AG"'
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DIA!0SIS
"A'AG"'T
CKD
Consernative
TRANSPLANT
4emodialisa Peritoneal
CAP) IP) 4emoltration 4emodialtration
Indication = vide A1I
$$T
Diaetes:Diaetes:
$/ 5 t & )RD$/ 5 t & )RD
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$/e 5ost ommon ause o& )RD$/e 5ost ommon ause o& )RD
Primary Diagnosis for Patients 0ho 3tart Dialysis
DiaKetes
,7&B
Hypertension
(6B
lomerulonephritis
&)B
5ther
&,B
#nite" )tates Rena( Data )ystem. 4nnua( "ata re'ort. 2000.
<o7 of patients
ProLection
9B CI
&98+ &988 &99( &99 (,,, (,,+ (,,8
,
&,,
(,,
),,
+,,
,,
,,
6,,
r (19978B
(+)'(+
(8&')
(,'(+,
< o 7 o f d i a l y s i s p a t i e n t s * t h o u s
a n d s .
ar"ioascu(ar 5orta(ity in t/ear"ioascu(ar 5orta(ity in t/e
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Genera( o'u(ation an" in )RDGenera( o'u(ation an" in )RD
$reate" y Dia(ysis$reate" y Dia(ysis
,7,&
&,,
&,
&
,7&
Annual mortality *B.
(-)+ +-+ -6+
8)-++ -+ 6-8+
%ale
!emale
/lac#0hite
Dialysis
eneral population
Age *years.
"A'AG"'T
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CKD
CONSER"ATI"E )IAL3SIS T$A'S1!A'T
Cadaver 1idn Living )onor
Related
$n related
Re&#! Rep!#$e"e&t T(e'#p)1
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Re&#! Rep!#$e"e&t T(e'#p)1
a. )ial&sis:. Peritoneal dial&sis 5continuous am'ulator& peritoneal
dial&sis
B CAP)6
. 4emod&alisis 54)6
'. RENAL TRANSPLANTATION)onor = Living 5related% un-related6
Cadaver
Resipien Tissue T&pe - 4LA-#atc7
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;ong term use o0 imuno(su++ressi1e drugs
to co+e *ith rejection
5 t $ 6
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5essa,es to $ae 6ome5essa,es to $ae 6ome
Kidney Disease is a silent -iller(no signs or
sym+toms until you loose <J8 o0 your -idney
0unction,
&he ris- o0 dying 0rom a cardio1ascular e1ent, i0
you1e lost 78 or more o0 your -idney 0unction,
is similar to that ha1ing had a heart attac-"
5roteinuria reduction needs to e a ke? 8art oflood 8ressure manaement"
J(,,7 American College of Physicians7 All "ights "eser@ed7
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