Ira Varianta 2010 2011

Acute Renal Failure
IRA si studentul la medicina

Stabilirea unei definitii medicale
Definitia insuficientei renale acute
(IRA)
IRA este un sindrom definit printr-un declin rapid al
ratei de filtrare glomerulara, caracterizat clinic de o
crestere impotanta a ureei si creatininei serice.

Oligoanuria este prezenta in 30-40% din cazuri. Unele
cazuri se pot prezenta cu poliurie.
IMPORTANTA IRA (AKI)
AKI is common.
AKI imposes a heavy burden of illness (morbidity
and mortality).
The cost per person of managing AKI is high.
AKI is amenable to early detection and potential
prevention.
There is considerable variability in practice

Dfinitii ?

Cratinine srique > 2 mg/dl
> 3 mg/dl
+ 44.2umol/L, Cr. de base < 221umol/l
+ 20% si Cr. de base > 221 umol/l (Singri,JAMA2003)
Doublement de la cratinine / dosage antrieur
/ admission
Dfaillance rnale de Knaus
Ure > 36 mmol/L
Cratinine > 310 mol/L
Diurse < 156 ml/8 h
< 479 ml/24 h
Ncessit d EER, mais prdfinir les critres!
IRA in ATI / reanimare
Criteriile RIFLE
Limitele criteriilor RIFLE
Aplicare neriguroasa a definitiei
Excluderea pac cu afectare renala
preexistenta

Neincluderea IRA- community acquired

Debitul urinar- f frecvent necuantificat
Acute and Chronic Kidney Disease
Conceptual model for integration of AKI, CKD, and AKD.
Overlapping ovals show the relationships among AKI,
AKD, and CKD. AKI is a subset of AKD. Both AKI and AKD without AKI can be
superimposed upon CKD.
Individuals without
AKI, AKD, or CKD have no known kidney disease (NKD).
Death
Conceptual Model for AKI
Complications
Normal
Increased
risk
Kidney
failure
Damage GFR
Antecedents
Intermediate Stage
AKI
Outcomes
AKI
KDIGO & AKI Guideline 2010
Definition and Staging of AKI
Increase in SCr by >0.3 mg/dl within 48 hours;
or
Increase in SCr by >1.5-fold above baseline,
which is known or presumed to have occurred
within 7 days; or
Urine volume <0.5 ml/kg/h for 6 hours.
Staging of AKI
Stage SCr Urine output
1 >1.5-1.9 times baseline
OR
0.3 mg/dl increase
<0.5 ml/kg/h for 6-
12 hours
2 >2.0-2.9 times baseline <0.5 ml/kg/h for >12
hours
3 >3.0 times baseline
OR
increase in SCr to >4.0 mg/dl
OR
RRT
<0.3 ml/kg/h for
24 hours
OR
Anuria for >12
hours
Insuficienta renala acuta
Incidenta -
1982, clinici nefrologie in UK
1237 cazuri in 12 luni
22.2 / 1,000,000 populatie

- Sfarsitul anilor 1980 in Scotia
71 / 1,000,000 populatie

1990s, Irlanda de Nord
127 / 1,000,000 populatie (40% au necesitat dializa)
Incidenta (cont.)
1990s, studiu prospectiv in comunitate (Feest)
Durata de 2 ani, inclusi 440,000 pacienti
creatinina > 500 umol/l
140 pmp / an
72% erau varstnici > 70 ani
Incidenta de 17 / pmp daca pacientii erau < 50ani
Incidenta de 949 pmp daca pacientii erau > 80 ani
supravietuire 54% la 12 luni, 34% la 2 ani
Beginning and Ending Supportive Therapy
for the Kidney
(BEST Kidney)
29 269 critically ill patients.
Acute renal failure in the critically ill:
a multinational study. JAMA. 2005 294(7):813-8.
5.7% (5.5 - 6.0%) had ARF.
72% were treated with RRT.
Overall hospital mortality: 60.3% (58 - 63%).
ETIOLOGIE
O larga varietate de patologii care pot aparea intr-o
larga varietate de situatii clinice

ETIOLOGIE
pre-renala
renala
post-renala
Tipurile principale de IRA
Insuficienta Renala Acuta
Cauze
pre-renale
Cauze renale
Cauze
Post-renale
Necroza tubulara Nefrita interstitiala
(10% cazuri)
Glomerulonefrite acute
(5% cazuri)
Ischemica
(50% cazuri)
Toxica
(35% cazuri)
Renala intrinseca
Vasculare GN
acute
Nefrita
interstitiala
acuta

Necroza
tubulara
acuta
Ischemica Nefrotoxica
Postrenala
Obstructia sistemului
colector sau a cailor
urinare extrarenale
Prerenala
1. Reducerea volum
circulant
2. Reducere relativa a
volumului circulant
(volum arterial ineficient)
3. Stenoza / ocluzie de
artera renala
4. Forme hemodinamice
Exogena Endogena
Vasculite, HTA
maligna,
poliangeita
microscopica

GN
postinfectioase,
Sdr Goodpasture
Nefrita interstitiala
asociata cu
medicamentele
Nefrotoxine :
1. Antibiotice (gentamicina)
2. substante de contrast
iodate
3. Cisplatina

1. Depunerea de pigmenti
intratubular (hemoglobinuria,
mioglobinuria)
2. depunere de proteine intratubular
(mielom)
3. depunere de cristale intratubular
(acid uric, oxalat)

- AINS
- IECA sau sartani in stenoza
unilaterala de artera renala sau
insuficienta cardiaca

hemoragii

insuficienta cardiaca
Strictura vezicala
Este IRA prerenala (functionala)
o conditie frecventa?
Necroza tubulara acuta 45%
IRA functionala 21%
IRC acutizata 13%
IRA obstructiva, postrenala 10%
Glomerulonefrite, vasculite 4%
Nefrita interstitiala acuta 2%
Cauze vasculare 2%
Sdr de insuficienta renala acuta
Dobandite in comunitate Dobandita in spital Dobandita in ATI
Incidenta Mica Moderata (5%) Mare (10-20%)

Cauza Unica Multipla MSOF
pre>post>renal pre>NTA>post MSOF + NTA

Supravietuire Buna Medie Redusa
70-90% 30-50% 10-30%
Schrier & Gottschalk, Diseases of the Kidney, 1996
Causes of AKI: Exposures and susceptibilities
KDIGO & AKI Guideline 2010
Cauze de IRA in spital
Aetiological factors contributing to ARF SCOTIA TOATE CAZURILE

Factors Patients
(%)
IRA (%) IRC A (%)
Sepsis 48.1 52.5 35.4
Hypotension 25.0 27.2 18.7
Post-surgical 21.5 24.2 13.9
Hypovolaemia 22.6 23.5 20.1
Nephrotoxins and
drug induced
12.5 11.8 14.4
Hepato-renal syndrome 7.5 9.3 2.4
Myocardial infarction 6.3 5.8 7.7
Rhabdomyolysis 5.6 7.2 1.0
Urinary obstruction 5.2 5.0 5.7
Glomerulonephritis 3.0 2.3 4.8
Pancreatitis 2.8 3.7 0.5
Myeloma 1.2 1.5 0.5
Beginning and Ending Supportive Therapy
for the Kidney (BEST Kidney)
Most common factor - septic shock 47.5% (45 - 49%).

30% of patients had pre-admission renal dysfunction.

Dialysis dependent survivors: 14% (11- 16%).
JAMA. 2005 294(7):813-8.
BEST Kidney
Independent risk factors for mortality:
use of vasopressors (OR, 1.95; (1.50-2.55) P<0.001),
mechanical ventilation (OR, 2.11; (1.58-2.82) P<0.001),
septic shock (OR, 1.36; (1.03-1.79) P = .03),
cardiogenic shock (OR 1.41; (1.05-1.90) P = 0.02),
hepatorenal syndrome (OR 1.87; (1.07-3.28) P = 0.03).
80
60
40
20
0
Mortalitatea in primul an la pacientii cu BRC
terminala raportata de ERA EDTA
Mortalitatea la pacientii dializati
pt IRA
1950 1960 1970 1980 1990
year
M
o
r
t
a
l
i
t
a
t
e

(
%
)

Evolutia mortalitatii in IRA vs IRC in Europa
Proportia de varstnici (> 80 ani) cu IRA
internati in ATI
1978 1980 1982 1984 1986 1988 1990 1992 1994 1996
0
10
20
30
40
50
Ani
P
r
o
c
e
n
t

d
e

v
a
r
s
t
n
i
c
i

d
i
n

n
u
m
a
r
u
l

t
o
t
a
l

I
R
A

1978 1980 1982 1984 1986 1988 1990 1992 1994 1996
10
20
30
40
50
Akposso et al Intens Care Med 26:400-406,2000
Effect of acute renal failure requiring renal replacement
therapy on outcome in critically ill patients
Metnitz PG et al.
Crit Care Med. 2002 Sep;30(9):2051-8.
ARF associated with four-fold
increased mortality
Controlled for underlying disease
severity using case controls
Mortality significantly higher in ARF
patients (62.8 vs. 38.5%)

Patofiziologia IRA

Teoria hemodinamica
Teoria celulara
Teoria interactiunilor celulare
Patofiziologia IRA

Teoria hemodinamica
Vascoconstrictia I/R
Obstructie tubulara
Retrodifuziune
IRA functionala
Blantz, KI, 53, 512-523, 1998.
Vasoconstrictie renala
si scaderea
coeficientului de ultrafiltrare
Deshidratare
Angiotensina II
Inervatie adrenergica
ADH
Insuficienta
cardiaca Sepsis
Oxid nitric
Prostaglandine
Scaderea RFG
Feedback tubuloglomerular
-
-
+
+
+
+
Fiziologie renala NORMALA
Autoreglarea
Ca urmare a reducerii perfuziei renale scade
tonusul arteriolei aferente I creste tonusul
arteriolei eferente
Procesul este ANGIOTENSIN II dependent
Permite mentinerea presiunii capilare
glomerulare si procesul de ultrafiltrare
Fiziologie renala
Feedback-ul tubuloglomerular
macula densa sesizeaza modificarile dependente de
flux si ale conc de Cl
-
in fluidul tubular
Fluxul plasmatic la nivelul nefronului se ajusteaza
prin alterarea rezistentei arteriolei aferente
Modificarile sunt dependente de SRAA, adenozina,
prostaglandine
Presiune de perfuzie renala (mm Hg)
F
l
u
x

s
a
n
g
v
i
n

r
e
n
a
l

r
e
l
a
t
i
v

(
%
)

150
100
50
0
0
50 100 150
Autoreglarea fluxului plasmatic renal
Normal
Ischemia
Mecanisme Protectoare
Autoreglarea renala
Eicosanoizi vasodilatatori NSAID
Angiotensina II ACE / AT
1
RA
Riscul de IRA la AINS
asociata cu anumiti factori de risc
OR 95% CI
No use of NSAID
1.0
Current use of NSAID
4.1 1.5-10.8
15-64 yrs old
1.0
> 65 yrs old
3.5 1.3-9.8
Recent hospitalization
6.9 2.9-16.2
Cardiovasular risk present
2.7 1.0-7.3
Other nephrotoxic drugs
4.0 1.4-11.4
Gutthann et al. Arch Int Med 156 2433-2439, 1996
(1)
Vasoconstrictie
Sistem renina angiotensina
Endotelina
PGI
2

NO
(2)
Obstructie
prin cilindri
(3)
Retrodifuzie
tublara
Ischemia
Nefrotoxine
Leziune tubulara
(tub contort proximal si ram
ascendent ansa Henle )
(5)
? Efect direct pe glomerul
GFR

Oligurie
flux tubular
Presiunea
intratubulara
Teoria hemodinamica (cont.)
(4)
Inflamatie
interstitiala
Anatomical and physiologic features
of the renal cortex and medulla.
Brezis & Seymour, The New Engl. J. of Med., 332,647-655, 1995.
Medullary rays
Cortical labyrinths
Blood flow
4.2 ml/min/g
Macula densa
Cortex
Renal vein
Renal artery
Medullary tick
ascending limbs
Blood flow
1.9 ml/min/g
Outer
medulla
Inner
medulla
PO2,
~ 50
mm Hg
PO2,
~ 10-20
mm Hg
Brezis et al, The Kidney, 1991.
Countercurrent exchange of
oxygen in the vasa recta
Heterogeneity of renal circulation
Cortical Medullary Junction:
ischemia/reperfusion
ISCHEMIE
Depletie ATP
REPERFUZIE
Acumulare de
hipoxantine
Xantine
Generare de
superoxid
Peroxid hidrogen
Radical hidroxyl
1) Stresul oxidativ
SOD
Crestere Ca
2+
citosolic

Activarea proteazei Ca
calmodulin dependente

Xantin oxidaza

Xantin
dehidrogenaza

Fe
2+
Fe
3+
Fenton reaction

2) Inflammatory
response
3) Rolul calciului
in leziunile de ischemie-reperfuzie renale.
Paller & Greene, Ann; Acad. Science, 723, 1994
Cell injury to hypoxic rat proximal is reduced by
chelation of extracellular Ca
2+
.
Wetzels et al, J. Pharmacol. Exp. Ther., 267, 176, 1993
A
B
Pathways of oxygen-derived
reactive species
Pathways of formation of reactive
nitrogen species
4) Role of NO
disparitia posibiltatii de vasodilatatie
Cytoskeletal Targets of NO
Microvillar Actin
Integrins
Basolateral
Membrane
NO
Lumen
NO
Induction of tubular epithelial cell injury
Patofiziologia IRA

Teoria hemodinamica
Vascoconstrictia I /R
Obstructie tubulara
Retrodifuziune
Aspectul microscopic in NTA
Potential cytoskeletal targets for proteases
during ischemia-reperfusion
Afectarea subletala a cel. tubulare renale determina exfolierea cel. epiteliale
viabile si adeziune intercelulara aberanta mediata de 1-integrina
( Noiri et al. Kidney Int 46:1050, 1994)
Niori et al, KI, 48, 1375-1385, 1995.
Normal renal epithelium
Sublethal injury
Presence of an excess of free RGD
Sediment urinar cu prezenta de cilindri
epiteliali la un pacient cu NTA
Tamm Horsefall protein
Embolie de colesterol la PBR
Caracteristicile majore ale embolizarii acute cu
emboli de colesterol
Exacerbarea brutala sau aparitia de novo a HTA
IRA progresiva cu evolutie diferita de a NTA
Afectare cutanata
Livedo reticularis
Gangrene
Cianoza/purpura
Febra
Durere lombara, abdominala, membre inferioare

Patofiziologia NTA
Teoria celulara
Pierderea polaritatii celulare
Necroza vs apoptoza
Recuperare prin factori de crestere ca IGF-1, HGF, EGF
Anatomia patologica in NTA-faza de recuperare
Recovering ATN showing a tubular epithelial cell mitotic figure (arrow).
Sutton et al Kidney Int 62:1539-1549,2002

CMJ hipoxie
Leziune microvasculara
Obstructie
Inflamatie
Coagulare
nediferentiere
Migrare
Proliferare
Rediferentiere
Repolarizare
Pierdere BBM
Exfoliere
Obstructie tubulara

Leziune
celulara
Fazele clinice si celulare in IRA ischemica
Intretinere
IRA CLINICA
IRA practica clinica corecta
Index inalt de suspiciune clinica
Semnele si simptomele clinice initiale sunt nespecifice
Determinarea bazala a ureei si creatininei plasmatice pentru
toate internarile in urgenta si TESTAREA REGULATA IN
TIMPUL SPITALIZARII
cuantificarea corecta intrari / iesiri, greutatea zilnica, TA in
clino- si ortostatism
Detectare/ recunoastere precoce si tratament prompt sau
transfer cu toate documentele si investigatiile imagistice
IRA practica clinica incorecta
Preluarea cazului de mai multi medici, fara continuitate in
urmarirea cazului
Absenta foii de observatie no charts / records
analize? Au fost cerute? Au fost vazute? S-a actionat in
consecinta?
Administrare de nefrotoxice; ignorarea determinarii
nivelelor serice ale medicamentelor
Fctie renala anormala ignorata pana vineri la ora 4.59pm
Transferul pacientilor fara supraveghere, documentare
corecta a cazului
2. afirmarea diagnosticului de insuficienta
renala ACUTA
IRA IRC
Istoric Retentie azotata absenta Dg anterior de nefropatie sau
HTA / anemie / nocturie
Examen clinic Modificari cutanate absente Modificari cutanate prezente.
HTA
Anemia Absenta sau redusa in raport
cu retentia azotata
Prezenta
Modificari radiologice
osoase
Absente Prezente, definitorii pentru
boala osoasa renala
Dimensiunile renale Normale Reduse, rinichi destructurat
Consecintele prezentei
HTA de lunga durata
Absente HTA prevalenta in 90% din
cazurile cu IRC
IRA este posibila obstructia de tract urinar?
DA !!!!!
La nivel prostata, uretra, vezica urinara, ureter, pelvis
renal
Cauze: litiaza, chirurgie, afectiuni ginecologice
Obstructia completa este cauza de anurie totala,
obstructia incompleta putand da alternanta
oligurie/poliurie
ATENTIE LA ASOCIEREA NTA + OBSTRUCTIE
IRA este posibila obstructia de tract urinar?

ECOGRAFIE DE URGENTA RENALA SI VEZICALA
hidronefroza
ureterohidronefroza
Distensie vezicala
Litiaza
Neoplazii, inclusiv limfoame (adenopatii)
Mase periaortice inflamatorii
IRA hidronefroza bilaterala
Nefrostomie bilaterala
Sau, din start, de ales rinichiul mai accesibil sau cu
dilatatie mai importanta, cu conditia sa existe cortex
renal pe acea parte (obstructia indelungata duce la
atrofie corticala severa cu pierderea functiei renale)
De retinut rolul diagnostic si prognostic al
nefrostomiei (exp. pionefroza)
IRA cauza posibila este GN?
GN acuta, LES, vasculitele sistemice
Prognosticul este mai usor daca se cunoaste diagnosticul
subiacent
Istoric complet si examen fizic
Microscopia urinii (din proba matinala, efectuata de medic)
Cilindri hematici
Determinarea de urgenta a ANCA, anti-GBM, ANA, VSH,
CRP
Daca este suspiciune de LES, adaugate: Ac ds-DNA-binding, C
3,
C
4

Acute renal failure
IRA este posibila o cauza vasculara?
Pacient varstnic, ateromatoza generalizata, fumator
Dimensiuni si functie renala asimetrica
Utilizarea IECA, deshidratare, prabusirea TA
Embolii cardiace (FA, boli valvulare), de la nivel arc
aortic (spontan; dupa cateterizare), al aortei
abdominale (similar anterior)

Diagnosticul pozitiv de
IRA prerenala
1. Afirmarea diagnosticului de insuficienta renala
2. Afirmarea dg. de IRA
3. Afirmarea dg. de IRA prerenala
A/ Context etiologic sugestiv
B/ Examen clinic sugestiv
C/ Confirmare paraclinica
Indicii urinari
Sedimentul urinar
Altele
D/ Proba terapeutica
renala acuta PRERENALA
A/ CONTEXT ETI OLOGI C SUGESTI V
A.1. Depletie reala a volumului extracelular
pierderi digestive: varsaturi, diaree, drenaj gastric
sau intestinal;
hemoragii exteriorizate
pierderi renale: exces de diuretice
pierderi respiratorii sau/si cutanate: transpiratii
profuze, arsuri;
A.2. Depletie relativa a volumului extracelular
sechestratie in al 3-lea sector: arsuri, zdrobiri tisulare,
pancreatite, ascita, ocluzie intestinala;
hemoragii ne-exteriorizate
A.3. Hipotensiune arteriala
Colaps circulator de orice cauza
Supradozaj de medicatie antihipertensiva
Reducerea prea brusca a TA (la varstnici)

A.4. Hipoperfuzie renala selectiva
Exces de IECA la pacienti cu stenoza bilaterala de artera renala
Exces de AINS pe fond de hipovolemie
Droguri vasoconstrictoare artera renala - ciclosporina
A.5. Stari edematoase
(combina hTA si hipoperfuzia selectiva renala)
Insuficienta cardiaca congestiva severa
Ciroza hepatica decompensata vascular
Sindromul hepato-renal
B/ EXAMEN CLI NI C
OBIECTIV CENTRAL = APRECIEREA STARII DE
DESHIDRATARE
Subiectiv: senzatie de sete, astenie
Obiectiv:
recenta a greutatii corporeale,
temperaturii cutanate
turgorului cutanat cu pliu persistent pretoracic,
mucoase uscate
hTA, TA fata de antecedente, pseudo-normalizarea TA,
modificari posturale patologice ale TA
jugulare plate, colaps al venelor peroferice,
presiunii intraoculare
oligurie cu urini concentrate
Confirmarea paraclinica a diagnosticului de
I RA prerenala:
C/ I NDI CI DI AGNOSTI CI URI NARI
Indicele urinar IRA prerenala IRA
parenchimatoasa
Na urinar (mEq/L) < 20 > 40
Uree / Cr. Plasmatica (*) 40-60 (>20) <20
Densitatea urinara > 1016 Hipostenurie
Osmolaritate urinara > 500 < 350
Osmolaritate u / p > 1.5 < 1.1
Uree u / p > 8 < 3
Creatinina u / p > 40 < 20
Fractia de excretie a Na < 1 > 1
Fractia de excretie a Na urinar
Definitie: procentul din totalitatea Na filtrat prin
glomerul care este excretat in urina
Na excretat = Na urinar x volumul urinar
Na filtrat = Na plasmatic x RFG
RFG = Cl. Creat = Cr.
U
x V / Cr.
P

FE Na = Na
U
x V / Na
P
x [(Cr.
U
x V):Cr.
P
] = Na
U
x
Cr.
P
/ Na
P
x Cr.
U

Confirmarea paraclinica a diagnosticului
de IRA prerenala:
Sedimentul urinar SARAC = fara celule,
cilindri, detritusuri celulare, proteinurie absenta

Dinamica creatininei zilnice cu fluctuatii
dependente de perfuzia renala vs crestere > 0.3-
0.5 mg/dL/zi (26-44umol/L/zi), tipica pentru NTA
Characteristics of an ideal biomarker
for AKI
Prioritatile terapeutice in IRA (I)
IRA - prognostic
Scorul Apache II nu este un element prognostic
Orice sistem local computerizat care poate da un
prognostic, poate fi validat daca este testat prospectiv
si independent in IRA de diverse etiologii, pe pacienti
cu varste variate, in alte unitati si spitale
IRA al cui teritoriu este ?
Nefrolog
Generalist
Intensivist
Chirurg?
Acute renal failure
ARF - what does it all cost?
20-25,000 per ITU patient (~ 25 days)
1

70,000 per ITU survivors leaving hospital (~ 90 days)
if 1200 cases per year, and 200 saved
ABOUT 35,000,000 / YEAR for ITU (E + W)
or 0.1% of the total NHS budget
1
{cf 20,000 per year per patient for maintenance dialysis}

Prioritatile terapeutice in IRA (I)
Identificarea si corectarea factorilor pre- si
postrenali
Revizuira medicatiei si stoparea nefrotoxicelor
Optimizarea debitului cardiac si a fluxului
plasmatic renal
Refacerea / cresterea fluxului urinar
Monitorizare zilnica ingesta/excreta, greutate
zilnica
GENERAL MANAGEMENT
IRA - PEUT-ON LA PREVENIR ?
IRA - PEUT-ON LA PREVENIR ?
Early goal-directed therapy in the treatment of severe sepsis and septic shock
(Rivers et al. N. Eng. J. Med. 2001; 345 : 1368-1377)

Early goal Standard
therapy therapy
(n = 130) (n = 130)

MODS* Baseline 7.6 3.1 7.3 3.1
6 h 5.9 3.7 6.3 3.7 p < 0.001
72 h 5.1 3.9 6.4 4 p < 0.001
Mortality 30.5 % 46.5 % p < 0.01

* Scale 0 - 24 (Marshall JC, Cook DJ. Crit. Care Med. 1995)

Mais, aucune valuation de la fonction rnale H72

IRA prerenala
TRATAMENT
OBIECTIV CENTRAL
Refacerea perfuziei renale prin:

Corectarea depletiei volemice absolute
sau
Corectarea perfuziei renale efective diminuate

REPREZINTA O URGENTA !
Prioritati terapeutice in IRA (II)
Identificarea si tratarea complicatiilor acute
(hiperkalemia, hiponatremia, acidoza, EPA)

Asigurarea suportului nutritional

Identificarea si tratarea agresiva a infectiilor

Initierea dializei inainte de aparitia complicatiilor
uremice

Adaptarea dozelor de medicamente la Cl. Crr.

Oprirea si repararea leziunilor celulare active
IRA tratamentul in urgenta al hiperkaliemiei
Lent, dar eliminare reala a K
Rasini schimbatoare ioni - calcium resonium (15 g po, 30 g
clisma)
Se poate continua un timp dar determina constipatie
(fortarea) diurezei
Limitata de functia renala si volumul urinar
Impune un volum urinar de > 1000 mls / 24 h
Excretia urunara de K
+
redusa de medicamente (IECA, amiloride,
spironolactona)
IRA de ce facem ceea ce facem ?
Corectie volemica
Diuretice de ansa
Mannitol
Dopamina
{aminofilina}
{CCB}
{factor natriuretic atrial}
Clase de dezechilibre hidrice in ATI
DRY-DRY
deshidratare
WET-DRY
-IC cu deshirdratare prin
tratatament diuretic si
hipoperfuzie renala
-IC cu hipoperfuzie renala
in ciuda hiperhidratarii
generale
DRY-WET
Spatiul trei: hiperhidratare,
darlichidul nu e in circulatie
WET-WET
Hiperhidratare
evidenta

MONITORING -
KEY TO SUCCESS
PA Catheter
Oesophageal doppler
Corectarea depletiei volemice
DEPLETIA VOLEMICA ABSOLUTA / REALA
Transfuzii sanguine atunci cand etiologia este hemoragica
sau oricand Hb < 10 g/L
Etiologie non-hemoragica sau in absenta sangelui:
Abord vascular central permite monitorizarea PVC; +/-
flexula de calibru mare (14G)
Determinarea PVC
PVC < 2 cm H2O volemia insuficienta, necesitand refacere
volemica
Solutii cristaloide vs coloide?
Immediate response:- Fluid resuscitation!
Daca PVC > 8 cm H2O, se opreste aportul sodat si se
reconsidera situatia tonicitatea si continutul electrolitic
al lichidelor de substitutie se modifica in functie de tipul
pierderilor si de dinamica constantele plasmatice

In formele cu hTA si PVC > 10 cm H2O se presupune
existenta unui soc cu rasunet cardiac si se recurge la
droguri cardiotonice sau/si vasoactive.
Corectia volemica ulterioara
functie de tipul pierderilor
Na K H HCO3 Cl
Secretie
gastrica
40-65 10 90

100-140
Fistula
pancreatica
135-155 5 70-90 55-75
Diaree 25-50 30-60 30-45 20-40
Transpiratii 30-50 5 45-55

La pacientii la care I RA este prerenala, diureza si functia
renala excretorie se vor ameliora semnificativ dupa
corectarea volumului intravascular si a TA.

Daca debitul urinar orar ramine scazut (< 30 ml/hr.), vor
fi utilizate si alte masuri pentru ameliorarea functiei
renale.
I. Status edematos cu volum intravascular redus
si redistribuirea fluidului spre compartimentul extravascular
(SN, ciroza, sepsis)

Obiectiv: rata diurezei = rata de reumplere vasculara

Metode: in cazurile refractare
escaladarea masurilor de promovare a diurezei
Solutii terapeutice pt I
1. Restrictie sodata
2. Diuretic de ansa in doza conventionala (furosemid 40 mg iv,
bumetanide 2 mg iv)
3. Diuretic de ansa in doze mari SI repetate (furosemid 200 mg
la 6 ore)
4. Diuretic tiazidic urmat la 30 min de diuretic de ansa in doza
mare
5. Diuretic de ansa in infuzie continua (furosemid 10-40 mg/hr)
6. Diuretic de ansa in doze mari diluat in albumina desodata
perfuzat in 30 minute la fiecare 6 ore.
7. Ultrafiltrare
II. Status edematos cu volum intravascular crescut +
vasconstrictie pre-renala,
secundara insuficientei cardiace
Obiectiv: compensarea cardiaca si cresterea debitului
cardiac
Metode:
presarcinii prin nitrati sau utilizarea diureticelor (in cazurile
refractare escaladarea masurilor de promovare a diurezei)
postsarcinii prin vasodilatatoare, atentie la IECA
Droguri inotrope pozitive
III. Vasoconstrictie prerenala directa (hipercalcemia,
radiocontrast, sdr. hepatorenal, ciclosporina)
Dopamina in doze de stimulare a receptorilor dopaminergici
1-3 ug/min/kg
Hidratare+diuretic de ansa
Blocante ale canalelor de Ca
Corticoizi, bifosfonati, calcitonina
Monitorizarea nivelului terapeutic al ciclosporinei
Antagonisti de endotelina

Diureticele de ansa
Ratiuni teoretice pentru utilizarea diureticelor de ansa:
inhiba pompa Na/K/Cl din lumenul ramurii groase
ascendente a ansei Henle, diminind astfel semnificativ
activitatea metabolica la acest nivel si deci necesarul de
oxigen;
cresc fluxul de urina intratubular, prevenind / reducind
obstructia tubulara;
inhiba procesul de feedback tubuloglomerular;
reduc rezistenta la nivelul vasculaturii renale si cresc astfel,
fluxul sanguin renal (mecanism mediat prin
prostaglandine).
Diuretice de ansa (furosemid, bumetanid)
Shilliday et al (NDT, 1997, 12)
Trial prospectiv, dublu-orb, placebo controlat care a folosit
diureticele de ansa la 278 pacienti cu cr > 180. End point-
uri: recuperarea functiei renale, dializa, decese
Diureticele de ansa in IRA:
trial dublu-orb, randomizat
0
10
20
30
40
50
60
Urine flow Renal rec Dialysis Death d21
Tora
Furo
Placebo
Shilliday et al. Nephrol Dial Transplant 11,1684,1996.
P
e
r
c
e
n
t

Diureticele, mortalitatea si lipsa de recuperare
a functiei renale in IRA
MEHTA et al. J AMA 288: 2547-2553, 2002
Curba de supravietuire Kaplan-Meier la pacientii
critici tratati fie cu albumina sau ser fiziologic.
SAFE study N Engl J Med 2004;350:2247-2256.

albumin
Mortalitatea globala in studiul SAFE la pacienti
critici (albumina vs ser fiziologic)
SAFE study N Engl J Med 2004;350:2247-2256.

IRA de ce facem ceea ce facem ??
Piv manitol
Diuretic osmotic potent
Creste volumul de filtrat tubular, efect de spalare
Reducerea edemului celulelor tubulare
Creste volumul plasmatic si reduce Ht
Actiune de scavanger al radicalilor liberi
Din nou, lipsa de date controlate
Vasopresoare
Supravietuirea
pacientilor cu soc septic
tratati cu vasopresoare
Martin et al Crit Care Med,
28: 2758-2765, 2000
Norepinephrine
Other vasopressors
Hospitalisation days
Efectul norepinefrinei asupra fluxului
urinar in socul septic
0
20
40
60
80
100
120
140
160
180
3h before 1st 3 hour
All patients
NE alone
NE+dob or dop
Norepinephrine dose and mortality
Norepinephrine dose (mg/kg/min)
<0.1
0.1-0.3
>0.3
Mortality (%)
20
24
76
Piv dopamina
Sinteza in mod fiziologic I tubii contorti proximali din L-Dopa
receptor DA-1 la nivel vase si tubi
Mai sensibili la dopamina
Determina vasodilatatie si scade reabsorbtia tubulara de Na
receptor DA-2 localizat la nivel terminatii nervoase simpatice.
Efectul piv dopamina la subiectii normali
DOrio et al, Arch. Int. Physiol. Biochim., 92, S11-S20, 1985
: DA1 receptor effect
renal blood flow
: receptor effect
cardiac index and heart rate
: receptor effect
systemic vascular resistance
index and arterial pressure
Meta-analiza: dopamina in doze mici creste fluxul urinar
dar nu previne disfunctia renala sau decesul
FRIEDRICH et al. Ann I ntern Med 142:510-24, 2005
Kidney I nternational (2006) 69, 16691674
'Low-dose' dopamine worsens renal perfusion in
patients with acute renal failure
A Lauschke et al
CCM 2006;34:589-597
Algoritm de tratament in cazul absentei raspunsului la corectia volemiei
Corectie pana la PVC 10 cm H2O
Da
Se reia furosemidul
Diureza se reduce
Se reia dopamina
Diureza se reduce Diureza se mentine
STOP dopamina
Diureza se mentine
STOP furosemid
Raspuns
Dializa
Absenta raspunsului
Infuzie furosemid 2-4 mig/min
dopamina 1-3 ug/kgc/min 4 ore
Absenta raspunsului Raspuns
Furosemid 80 mg iv bolus
Nu
Pacient hipovolemic
IRA oligurica < 30 ml/h
Aminofilina
Actioneaza pe receptorii renali de adenozina si inhiba
fosfodiesteraza
Creste fluxul plasmatic renal, reduce reactivitatea
vasculara
CCB
Limiteaza fluxul intracelular de Ca
++

Multe date pe animale, efect maxim daca se
administreaza anterior agresiunii
Influenta ACC asupra functiei renale dupa expunere
la substante de contrast iodate
Tepel et al. NEJM 343,2000
Trialuri clinice recente
Factori de crestere - IGF I
Factor natriuretic atrial - ANF
Antagonistii receptorilor endotelinei
tiroxina
PGE
1

What therapies MIGHT alter the outcome in acute renal failure?

There will not be a single answer
but given what we know of pathophysiology, what might
help in some cases (if we knew which to go for)?

Prevention of renal vasoconstriction
Growth factors
Stem cells
Fenoldopam and ARF in sepsis
84
86
88
90
92
94
96
98
100
102
104
106
1 3 5
Placebo
Fenoldopam
Morelli et al, Crit Care Med, 2005
days
Screa (mol/l)
Prevention of vasoconstriction
Fenoldopam dopamine A-1 receptor agonist

Systematic review of RCTs in ICU or major surgery
16 studies, 1290 patients

Reduced risk of acute kidney injury OR 0.43 (0.32-0.59)
Reduced need for RRT OR 0.54 (0.34-0.84)
Reduced in hospital death OR 0.64 (0.45-0.91)
Stimulation of regeneration
rhIGF-1, man
IGF-1 studii clinice/rezultate
Franklin et al.(AJP 272:F257, 1997) a administrat IGF-1
(100g/kg s.c. la 12 hr x 6 doze) sau placebo imediat dupa
chirurgia aortei suprarenal sau a arterei renale la to 54
pacienti. Nici unul nu a dezvoltat IRA. Reducerea
postoperatorie a RFG a aparut mai rar la pacientii care au
primit IGF-1 (22 vs 33%).
Hirschberg et al. (Kidney Int 55: 2423,1999) a administrat
IGF-1 sau placebo (100g/kg s.c. la 12 hr x 14 zile) la 72
pacienti cu IRA constituita de etiologie mixta. Nu au fost
diferente intre RFG, Cr serica, flux urinar sau mortalitate
intre cele 2 grupuri.
Stimulation of regeneration epo: how might it work in ATN?
Stimulation of regeneration epo at time of ischaemic renal
injury (animal)
Stimulation of regeneration epo 6 hours after ischaemic renal
injury (animal)
Stimulation of regeneration epo in patients with ATN
receiving renal replacement therapy

Retrospective cohort study (not RCT) on ICUs of Washington University
hospital

Epo (71 patients); no epo (116 patients)

No effect on requirement for blood transfusion when adjusted for baseline
haemoglobin

No effect on renal recovery OR 0.63 (0.30-1.3)
Stimulation of regeneration
HUVEC infusion immediately
after ischaemic renal injury
(animal)
Stimulation of regeneration infusion of cells that do and do
not express eNOS immediately after ischaemic renal injury
(animal)

HEK = Human Embryonic Kidney
WT = wild type
G2A = transfected with deficient
eNOS
eNOS = transfected with active
eNOS
Factor natriuretc atrial
ANARITIDE study
Allgreen et al, NEJM, 1997, 336, 828-834
504 pacienti din ATI cu IRA, randomizati sa primeasca 24 h
ANP sau placebo
Util in grupul oliguric (55/60 necesita dializa vs. 44/60 dupa
ANP, p = 0.008)
? Daunator in alte cazuri (79/195 necesita dializa vs. 95/183
after ANP, p = 0.03)
21-Day Dialysis-Free Survivorship.
0
20
40
60
80
100
All subjects (n=504) Oliguric (n=121) Non-oliguric (n=376)
Placebo
Anaritide (atrial natriuretic peptide)
%
* p=0.005 A vs. P
Lewis et al, AJKD 2000
Coagulation
Anticoagulant Procoagulant
COAGULATION
TFPI
Thrombin
Prothrombin
TF
Xa X
IXa IX
VIIa
ATIII
T-ATIII complexes
(-)
TM - thrombin
(-)
Degrades
Va, VIIIa
PC APC + PS
30.8%
24.7%
19.4%
relative
redn
Treatment of hypotension in septic
shock
Fluids Definitely
Inotropes Definitely but.
Others
Activated protein-c Yes (cost!!!)
French multi-centre PRCT (n=299) - just completed
Low dose hydrocortisone (50 qds) + fludrocortisone
in early septic shock (within 6 hours)
significant reduction in relative mortality!!
European multi-centre PRCT underway
Steroids and sepsis good news ?
28-DAY SURVIVAL IN SEPTIC SHOCK (n=299)
p=0.01
TREATMENT 47%
0 7 14 21 28
days
0.0
0.2
0.4
0.6
0.8
1.0
PLACEBO 39%
ALL PATIENTS
C
u
m
u
l
a
t
i
v
e

s
u
r
v
i
v
a
l

r
a
t
e

shock
Fluids Definitely
Others
Steroids Probably
Methylene blue
* NO scavenger
* NOS inhibitor
* 2 mg/kg over 15
* 50% respond
shock
Fluids Definitely
Others
Steroids Probably
Methylene blue ? rescue
Vasopressin
Acts on V
1
and V
2
receptors
V
2
receptors collecting tubules - water resorbtion
V
1
receptors vascular smooth muscle - vasoconstriction
Anti-diuretic action/regulation of plasma
osmolarity (5-10 pg/ml)
Levels are dramatically increased
(often >100 pg/ml) early in stress

Vasopressin
VP levels very low later in septic shock
3 vs. 22 pg/ml in cardiogenic shock
(Landry et al, Circulation 1997)
BP restored by small bolus doses of VP
or low dose infusion (0.01-0.04 U/min)
infusions up to 0.26 U/min had no pressor effect in
normal humans
shock
Fluids Definitely
Others
Activated Protein-c Yes (cost!!!)
Steroids Probably
Methylene blue ? rescue
Vasopressin.maybe
Rivers et al, NEJM 2001; 345: 1368-77
Rivers et al, NEJM 2001; 345: 1368-77
Van Den Berghe et al, NEJM 2001; 345: 1359-67
1548 admissions to 1 surgical ICU (Belgium) in 1 yr
Randomised to receive insulin to keep blood sugar at:
80-110 mg/dl [4-6 mmol/l] or
standard Rx of 180-200 mg/dl [9-11 mmol/l])
Mortality reduced from 8 to 4.6% (p<0.05)
MOF with proven septic focus: 33 vs. 8 deaths
MOF w/o detectable septic focus: 18 vs 14 deaths
Dialysis/CVVHF: 64 (8.2) vs 37 (4.8)
Van Den Berghe et al, NEJM 2001; 345: 1359-67
Experimental Therapies in ARF
Before Injury After Injury
Haemodynamic Diuretics ACEI
Mannitol PDE inhibitors
Dopamine ANP
Ca
2+
antag. Endothelin antag.

Cell Injury SOD anatag. PAF antag.
anti-sense iNOS ICAM-1 antibody
P-selectin antag. a-MSH
CTLA-4Ig
RGD peptides

Cell repair IGF-1, EGF, HGF IGF-1
Concluzii
Cercetarea elaborata si intensiva in NTA a dus la o
intelegere mai buna a proceselor implicate
In ciuda noilor cunostinte, nici un nou agent
terapeutic nu si-a dovedit eficienta in conditii clinice.
prevenirea si tratamentul precoce ale IRA/NTA sunt
inca cele mai eficiente masutri terapeutice.
Suportul nutritional in IRA
Mild Moderate Severe
Energy
substrates
glucose glucose + fat glucose + fat
AA/ protein
(g/Kg/day)
0.6 - 0.8
EAA (+NEAA)
0.8 - 1.2
EAA + NEAA
1.0 + 1.5
EAA + NEAA
Nutrients
used
enteral
formulae
glucose
50 - 70 %
glucose
50 - 70%
Marimea catabolismului
Fat emulsion 10 or 20%
ARF Nutritie

CATABOLISMUL ESTE REGULA
Dat de rezistenta la insulina, efectul TSR, acidoza
Necesarul de calorii creste si mai mult daca pacientul
este septic
Mortalitatea este direct proportionala cu balanta
azotului
Nu sunt date controlate care sa sustina efectul benefic
al suportului nutritional asupra supravietuirii.
ARF Nutritie
Alti factori
Nr calorii / unitate volum
Na, K, PO4 (reduce)
Substante minerale (adaugate)
De preferat calea enterala daca intestinul este
functional
35 Kcal, 1g proteine, 0.16g N / kg corp
Dialytic management of ARF
Johannes the baptist
IRA terapii de supleere renala
Indicatii de initiere

Oligurie (< 500 mls / d)
urea > 30 mmol/l
creatinina > 1000 umol/l
potasiu > 6.5 mmol/l
pH < 7.2
EPA refractar
Pericardita uremica
Encefalopatie uremica

- Conditii tehnice de realizare
Instituire rapida si usoara
Eficienta
Controlul volumului, fara limitarea alimentarii
Corectia acidozei

- Conditii tehnice de realizare
Biocompatibilate
Necesitati minime de anticoaglare sistemica sau regionala
Efect minim/ absent asupra functiei renale, duratei IRA
Efect minim/absent asupra stabilitatii hemodinamice
Efecte farmacocinetice previzibile
Odds ratio 0.5 1 1.5 2.0 2.5 3
RCTs only
Cellulose-acetate
Cuprophane
Subramanian et al, KI, 62, 1819-1823, 2002
Supravietuire: membrane
bio-incompatibile vs bio-compatibile
Principii si optiuni
Convectie vs difuzie
Continua sau intermitenta
Membrane de celuloza sau sintetice
Acces vascular (arterial, venos, pompa de sange)
Utilizarea de fluid de inlocuire
Necesitatea si durata anticoagularii
{dializa peritoneala}
HD intermitenta
De trei x/sapt
Zilnica
high-flux
Hemofiltrare
Hemodiafiltrare
{Ultrafiltrare}

difuzia
In hemodializa
Foloseste membrane semipermeabile, pori de dimensiuni
mici
Gradient de presiune arterio-venos
Deplasare transmembrnara bidirectionala
intermitenta
Frecvent efecte hemodinamice
Clearance limitat (proportional cu durata)

convectia
Solvit deplasat prin membrana semipermeabila impreuna cu
solventul prin filtrare determinata de gradient de presiune
transmembranar
Membrana cu porii foarte mari
Este de obicei o terapie continua
Impune utilizarea de lichid de inlocuire
Permite o epurare eficienta
Poate fi combinata cu dializa in contra-curent in
hemodiafiltrare

Utilizarea IHD si a CRRT
0
10
20
30
40
50
60
70
80
Never <10 11-25 26-50 51-75 >75
CRRT
IHD
PD
% of ARF patients
%

o
f

n
e
p
h
r
o
l
o
g
i
s
t
s

Mehta et al, Am J Nephrol, 1999
Terapia de supleere renala
continua pt pacientii cu IRA
Avantaje
Ameliorarea stabilitatii
hemodinamice
Reducere aritmii cardiace
Ameliorare nutritie
Ameliorare schimburi gazoase
pulmonare
Ameliorare comtrol fluide
Ameliorare parametrii biochimici
Sedere mai scurta in ATI
Dezavantaje
Probleme abord vascular
Risc crescut de sangerare
Imobilizare prelungita
Frecvent, ruperea capilarelor
filtrului
Cost ridicat
Acidoza lactica la utilizarea de
solutii lactat
Pe primul plan ,
Eficienta
Clearanceul de uree necesar in CCRT pt
atingerea controlului corespunzator al
azotemiei la pacientii cu IRA.
Frecventa IHD necesara pt atingerea
controlului corespunzator al azotemiei la
pacientii cu IRA.
2000
1000
0
U
r
e
a

c
l
e
a
r
a
n
c
e

(
m
l
/
h
r
)

50 60 70 80 90 100 50 60 70 80 90 100
Weight (Kg)
Weight (Kg)
7
6
5
4
3
2
I
H
D

F
r
e
q
u
e
n
c
y

(
p
e
r

w
e
e
k
)

100 mg/dL
80 mg/dL
60 mg/dL
Clark et al, JASN, 8, 804-812, 1997.
60 mg/dL
80 mg/dL
100 mg/dL
Efectul dozei de dializa asupra supravietuirii
100
75
50
25
0
%

s
u
r
v
i
v
a
l

0 2 4 6 8 10 12 14 16 18 20
CCF ICU ARF Score
low Kt/V
urea
high Kt/V
urea
CCF score outcome
Leblanc M, Paganini E Adv Ren Repl Ther 2: 255, 1995
Stabilitatea hemodinamica
-10
20
50
80
110
CAVH IHD
Mean Map
Maxi fall
Map
Misset et al, Int Care Med, 22, 742, 1996
p=NS
0 6 12 18 24
50
100
150
TNF
IL-1b
IL-6
*
*
* p<0.05
Time (hours)
p
l
a
s
m
a

c
o
n
c
e
n
t
r
a
t
i
o
n
,

%

o
f

t
=
0

Indepartarea citokinelor: studii clinice
De Vriese & Lameire, J Am Soc Nephrol 1999
HD zilnica si prognosticul pacientilor cu IRA
Schiffl et al NEJM 346: 305-310, 2002
HD zilnica si prognosticul pacientilor cu IRA
Schiffl et al NEJM 346: 305-310, 2002

Prognosticul imediat CRRT vs
IHD
0
10
20
30
40
50
60
70
ICU mortality Hospital mortality
All
CRRT
IHD
N= 166
P= 0.02 P=0.02
Mehta et al, Kidney Int, 2001, 1154-1163
%
Prognosticul pe termen lung al
TSR la IRA in ATI
0
10
20
30
40
50
60
70
80
90
All patients Survived
hospital at
6mnth
Survived
6mnth at 12
mnth
Survived
Died
N=979
Morgera et al, AJKD 40, 275-279, 2002
%
CRRT: dezavantaje
sangerare
Cost
Inconvenienta
Greseli in aprecierea balantei hidrice
Tulburari electrolitice
Hipotermia
IHD clasica 4 h, 3 ori/sapt

hemodiafiltrare lenta
(adaptabila si zilnica)

CVVHD cu volume mari
CVVHD
CVVH
CAVHD
CAVH

CRRT
clasic
Slow Extended Daily Dialysis
Ofera alegerea intre avantajele unui monitor IHDF
(eficienta mare, cost mic, control precis al
ultrafltrarii) combinate cu aavantajele CRRT (durata
mare de tratament, control metabolic) intr-o maniera
modulara, utilizand un singur tip de aparat
Slow Extended Daily Dialysis
Impune evaluare zilnica in echipa nefrolog si
intensivist
Adaptatarea
Timp de dializa : de la HD continua la IHD
Fluxului de sange si dializat pe aparat
A ratei de hemofiltrare
Functie de necesitatile pacientului
Comparatia MAP in timpul EDD vs. CVVH.
0
10
20
30
40
50
60
70
80
90
100
preMAP midMAP endMAP
CVVH
EDD
Kumar et al, AJKD, 36, 294-300, 2000
P=NS
P=NS P=NS
SLEDD: anticoagulare
0
5000
10000
15000
20000
25000
30000
35000
Lowest dose Median dose Highest dose
SLEDD
CVVH
H
e
p
a
r
i
n

n
e
e
d

i
n

u
n
i
t
s
/
d
a
y

Kumar et al, AJKD, 36, 294-300, 2000
No heparin: 31.9% in SLEDD vs 2.7% in CCVH (p<0,05)
IHD vs CRRT in IRA: concluzii
Nu este demonstrata nici o superioritate a CRRT vs
IHD
Performanta IHD se poate ameliora prin: dializa
zilnica, HDF, tratament prelungit
Evolutia catre terapii hiobrid este normala (SLEDD)
Recomandari actuale de tratament in IRA
HD intermitenta
Tratament de electie in IRA izolata , dar poate fi utilizata si in
MSOF
Asigurarea unei doze suficiente de dializa; este de preferat HD
zilnica
Se poate utiliza orice membrana (exceptie rabdomioliza sau
substante contrast iodate High-Flux)
CRRT
Preferata in instabilitatea cardiocirculatorie, hiperhidratare, edem
cerebral
Asigurarea unei doze suficiente de dializa (35 ml/kgh recomandata
in CVVH )
Slow extended daily dialysis (SLEDD)
Combina unele din avantajele CRRT si IHD
Considerabil mai ieftina decat CRRT

Determinanti majori ai terapiei:
Experienta personala
Disponibilitatile locale / circumstante locale
Recomandari actuale de tratament in IRA
Concluzii
Pacientii cu IRA necomplicata au prognosy=tic
bun cu HD conventionala
Desi initiatorii CRRT raporteaza avantajeale
tratamentului, nu a putut fi demonstrat un
beneficiu major asupra supravietuirii la acesti
pacienti
Individualizarea prescriptiei de dializa alaturi de
experienta fiecarui centru in parte determina cele
mai bune solutii pt fiecare centru de dializa in
parte
A. Jrres 09-2005
A. Jrres 09-2005

Ira Varianta 2010 2011

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Ira Varianta 2010 2011

Uploaded by

Copyright:

Available Formats

Acute Renal Failure

IRA si studentul la medicina

You might also like