Acute Renal Failure

Acute Renal Failure
IRA si studentul la medicina
Stabilireauneidefinitiimedicale
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
IRA in ATI / reanimare

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 dEER, mais prdfinir les critres!
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).
Conceptual Model for AKI

Complications
Complications
AKI
Normal
Normal
Increased
Increased
risk
risk
Damage
Damage
GFR
Kidney
failure
Antecedents
Intermediate Stage
AKI
Outcomes
KDIGO & AKI Guideline 2010
Death
Death
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
>1.5-1.9 times baseline

OR
0.3 mg/dl increase
<0.5 ml/kg/h for 612 hours
>2.0-2.9 times baseline
<0.5 ml/kg/h for >12

hours
>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.
5.7% (5.5 - 6.0%) had ARF.
72% were treated with RRT.
Overall hospital mortality: 60.3% (58 - 63%).
Acute renal failure in the critically ill:
a multinational study.
JAMA. 2005 294(7):813-8.

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
Necroza tubulara
Ischemica
(50% cazuri)
Cauze renale
Nefrita interstitiala
(10% cazuri)
Toxica
(35% cazuri)
Cauze
Post-renale
Glomerulonefrite acute
(5% cazuri)

Prerenala
1. Reducerea volum
circulant
hemoragii
2. Reducere relativa a
volumului circulant
(volum arterial ineficient)
Renala intrinseca
Vasculare
Vasculite,
HTA maligna,
poliangeita
microscopica
insuficienta cardiaca
GN
acute
GN
postinfectioase,
Sdr Goodpasture
Nefrita
interstitiala
acuta
Nefrita interstitiala
asociata cu
medicamentele
Postrenala
Necroza
tubulara
acuta
Ischemica
Obstructia sistemului
colector sau a cailor
urinare extrarenale
Strictura vezicala
Nefrotoxica
3. Stenoza / ocluzie de
artera renala
4. Forme hemodinamice
- AINS
- IECA sau sartani in stenoza
unilaterala de artera renala sau
insuficienta cardiaca
Exogena
Nefrotoxine :
1. Antibiotice (gentamicina)
2. substante de contrast
iodate
3. Cisplatina
Endogena
1. Depunerea de pigmenti
intratubular (hemoglobinuria,
mioglobinuria)
2. depunere de proteine intratubular
(mielom)
3. depunere de cristale intratubular
(acid uric, oxalat)
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
Mica
Dobandita in spital
Moderata (5%)
Dobandita in ATI
Mare (10-20%)
Cauza
Unica
pre>post>renal
Multipla
pre>NTA>post
MSOF
MSOF + NTA
Supravietuire
Buna
70-90%
Incidenta
Medie
30-50%
Redusa
10-30%
Schrier & Gottschalk, Diseases of the Kidney, 1996
Causes of AKI: Exposures and susceptibilities
KDIGO & AKI Guideline 2010
Sepsis
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).
Evolutia mortalitatii in IRA vs IRC in Europa

80
Mortalitate (%)
60
Mortalitatea la pacientii dializati
pt IRA
40
20
Mortalitatea in primul an la pacientii cu BRC

terminala raportata de ERA EDTA
1950
1960
1970
year
1980
1990
Proportia de varstnici (> 80 ani) cu IRA

internati in ATI
Procent de varstnici din
numarul total IRA
50
50
40
40
30
30
20
20
10
10
1978
1978 1980
1980 1982
1982 1984
19841986
19861988
19881990
19901992
19921994
1994 1996
1996
Ani
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
Insuficienta
cardiaca
Deshidratare
Angiotensina II
+
Inervatie adrenergica
+
ADH
Sepsis
Oxid nitric
Vasoconstrictie renala
si scaderea
coeficientului de ultrafiltrare
Prostaglandine
Feedback tubuloglomerular
Scaderea RFG
Blantz, KI, 53, 512-523, 1998.

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
Autoreglarea fluxului plasmatic renal
Flux sangvin renal relativ (%)
150
Ischemia
100
Normal
50
0
0
50
100
Presiune de perfuzie renala (mm Hg)
150

Mecanisme Protectoare
Autoreglarea renala
Eicosanoizi vasodilatatori
Angiotensina II
NSAID
ACE / AT1RA
Riscul de IRA la AINS

asociata cu anumiti factori de risc
OR
N
o
u
s
e
o
f
N
S
A
I
D
1
.
0
Curr1
e5
n-t6u
s
e
o
f
N
S
A
I
D
4
.
1
4
y
r
s
o
l
d
1
.
0
>
6
5
y
r
s
o
l
d
3
.
5
R
e
c
e
n
t
h
o
s
p
i
t
a
l
i
z
a
t
i
o
n
6
.
9
Cardiovasularriskpresent 2.7
95%CI
1.5-10.8
1
.
3
9
.
8
21.9
-.0-176.3
.2
Gutthann et al. Arch Int Med 156 2433-2439, 1996
Teoria hemodinamica (cont.)

Leziune tubulara
(tub contort proximal si ram
ascendent ansa Henle )
Ischemia
Nefrotoxine
(1)
Vasoconstrictie
Sistem renina angiotensina
Endotelina
PGI2
NO
(5)
? Efect direct pe glomerul
(2)
Obstructie
prin cilindri
Presiunea
intratubulara
GFR
(3)
Retrodifuzie
tublara
(4)
Inflamatie
interstitiala
flux tubular
Oligurie
Anatomical and physiologic features

of the renal cortex and medulla.
Blood flow
4.2 ml/min/g
Cortical labyrinths
Macula densa
PO2,
~ 50
mm Hg
Medullary rays
Blood flow
1.9 ml/min/g
Outer
medulla
PO2,
~ 10-20
mm Hg
Inner
medulla
Medullary tick
ascending limbs
Cortex
Renal vein
Renal artery
Brezis & Seymour, The New Engl. J. of Med., 332,647-655, 1995.
Heterogeneity of renal
circulation
Countercurrent
exchange of
oxygen in the vasa
recta
Brezis et al, The Kidney, 1991.
Cortical Medullary Junction:
ischemia/reperfusion
ISCHEMIE
Depletie ATP
REPERFUZIE
Acumulare de
hipoxantine
Xantine
Generare de
superoxid
SOD
Crestere Ca2+ citosolic

Peroxid hidrogen
Xantin oxidaza
Fe2+
Fenton reaction
Fe3+
Activarea proteazei Ca
calmodulin dependente
Radical hidroxyl
Xantin
dehidrogenaza
1) Stresul oxidativ
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 Ca2+.
Wetzels et al, J. Pharmacol. Exp. Ther., 267, 176, 1993
4) Role of NO
A
Pathways of oxygen-derived
reactive species
Pathways of formation of reactive

nitrogen species
disparitia posibiltatii de vasodilatatie
Induction of tubular epithelial cell injury

Microvillar Actin
NO
NO
Lumen
Integrins
Cytoskeletal Targets of NO
Basolateral
Membrane
Patofiziologia IRA
Teoria hemodinamica
Vascoconstrictia I/R
Obstructie tubulara
Retrodifuziune
Aspectul microscopic in NTA
Potential cytoskeletal targets for proteases

during ischemia-reperfusion
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).
Fazele clinice si celulare in IRA ischemica

Pre
re
nal
a
Initiere
Leziune
celulara
Pierdere BBM
Exfoliere
Obstructie tubulara
ie
ns
te
Ex
CMJ hipoxie
Leziune microvasculara
Obstructie
Inflamatie
Coagulare
Intretinere
nediferentiere
Migrare
Proliferare
Sutton et al Kidney Int 62:1539-1549,2002
Re
tie
a
r
pa
Rediferentiere
Repolarizare

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, C4
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 ETIOLOGIC SUGESTIV
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 CLINIC
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

IRA prerenala:
C/ INDICI DIAGNOSTICI URINARI
Indicele urinar
IRA prerenala
IRA
parenchimatoasa
Na urinar (mEq/L)
Uree / Cr. Plasmatica (*)
< 20
40-60 (>20)
> 40
<20
Densitatea urinara
> 1016
Hipostenurie
Osmolaritate urinara
Osmolaritate u / p
Uree u / p
> 500
> 1.5
>8
< 350
< 1.1
<3
Creatinina u / p
Fractia de excretie a Na
> 40
<1
< 20
>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 = NaU x V / NaP x [(Cr.U x V):Cr.P] = NaU x

Cr.P / NaP 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 > 0.30.5 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)
MODS* Baseline
6h
72 h
Mortality
* Scale
Early goal
therapy
(n = 130)
Standard
therapy
(n = 130)
7.6 3.1
5.9 3.7
5.1 3.9
7.3 3.1
6.3 3.7
6.4 4
30.5 %
0 - 24 (Marshall JC, Cook DJ. Crit. Care Med. 1995)
Mais, aucune valuation de la fonction rnale H72
p < 0.001
p < 0.001
46.5 %
p < 0.01
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
MONITORING KEY TO SUCCESS
Oesophageal doppler
PA Catheter
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
HCO3
Cl
Secretie
gastrica
40-65
10
90
Fistula
pancreatica
135-155
70-90
55-75
Diaree
25-50
30-60
30-45
20-40
Transpiratii
30-50
100-140
45-55

La pacientii la care IRA 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 pointuri: recuperarea functiei renale, dializa, decese
Diureticele de ansa in IRA:

trial dublu-orb, randomizat
60
Percent
50
40
Tora
Furo
Placebo
30
20
10
0
Urine flow
Renal rec
Dialysis
Death d21
Shilliday et al. Nephrol Dial Transplant 11,1684,1996.
Diureticele, mortalitatea si lipsa de recuperare

a functiei renale in IRA
MEHTA et al. JAMA 288: 2547-2553, 2002
Curba de supravietuire Kaplan-Meier la pacientii

critici tratati fie cu albumina sau ser fiziologic.
albumin
SAFE study N Engl J Med 2004;350:2247-2256.
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
Patient survival
Supravietuirea
pacientilor cu soc septic
tratati cu vasopresoare
Norepinephrine
Other vasopressors
Martin et al Crit Care Med,

28: 2758-2765, 2000
Hospitalisation days
ml.h
Efectul norepinefrinei asupra fluxului

urinar in socul septic
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
: DA1 receptor effect

renal blood flow
: receptor effect
cardiac index and heart rate
: receptor effect
systemic vascular resistance
index and arterial pressure
DOrio et al, Arch. Int. Physiol. Biochim., 92, S11-S20, 1985
Meta-analiza: dopamina in doze mici creste fluxul urinar

dar nu previne disfunctia renala sau decesul
FRIEDRICH et al. Ann Intern Med 142:510-24, 2005
Kidney International (2006) 69, 16691674
'Low-dose' dopamine worsens renal perfusion in

patients with acute renal failure
A Lauschke et al
CCM 2006;34:589-597
A lg o r itm d e tr a ta m e n t in c a z u l a b s e n te i r a s p u n s u lu i la c o r e c tia v o le m ie i
IR A o lig u r ic a < 3 0 m l/h
P a c ie n t h ip o v o le m ic
D a
N u
C o r e c tie p a n a la P V C 1 0 c m H 2 O
F u r o s e m id 8 0 m g iv b o lu s
A b s e n ta r a s p u n s u lu i
In f u z ie f u r o s e m id 2 - 4 m ig /m in
d o p a m in a 1 -3 u g /k g c /m in 4 o r e
R aspuns
A b s e n ta r a s p u n s u lu i
S T O P fu r o s e m id
D ia liz a
D iu r e z a s e r e d u c e
D iu r e z a s e m e n tin e
S e r e ia fu r o s e m id u l
S T O P d o p a m in a
D iu r e z a s e r e d u c e
S e r e ia d o p a m in a
D iu r e z a s e m e n tin e
R aspuns

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
PGE1
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

Screa (mol/l)
106
104
102
100
98
96
94
92
90
88
86
84
Placebo
Fenoldopam
days
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 IGF1 (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.

100
Placebo
80
Anaritide (atrial natriuretic peptide)
60
40
20
0
All subjects (n=504)
* p=0.005 A vs. P
Oliguric (n=121)
Non-oliguric (n=376)
Lewis et al, AJKD 2000
Coagulation
Anticoagulant
Procoagulant
COAGULATION
TMthrombin
PC
APC+PS
ATIII
TFPI
Degrades
Va,VIIIa
TATIIIcomplexes
()
()
Thrombin
XaX
VIIa
TF
IXaIX
Prothrombin
24.7%
30.8%
19.4%
relativ
e redn
Treatment of hypotension in septic

shock
Fluids
Inotropes
Others
Definitely
Definitely but.
Activated protein-c Yes (cost!!!)
Steroids and sepsis good news ?
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
28-DAY SURVIVAL IN SEPTIC SHOCK (n=299)

ALL PATIENTS
Cumulative survival rate
1.0
0.8
0.6
TREATMENT 47%
0.4
PLACEBO 39%
0.2
0.0
p=0.01
0
14
days
21
28

shock
Fluids
Inotropes
Others
Definitely
Definitely but.

Steroids
Probably
Methylene blue
* NO scavenger
* NOS inhibitor
* 2 mg/kg over 15
* 50% respond

shock
Fluids Definitely
Inotropes
Definitely but.
Others
Steroids
Probably
Methylene blue
? rescue
Vasopressin
Acts on V1 and V2 receptors
V2 receptors collecting tubules - water resorbtion
V1 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
Inotropes
Others
Definitely
Definitely but.
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
Diuretics
Mannitol
Dopamine
Ca2+ antag.
After Injury
ACEI
PDE inhibitors
ANP
Endothelin antag.
Cell Injury
SOD anatag.
anti-sense iNOS
P-selectin antag.
CTLA-4Ig
RGD peptides
PAF antag.
ICAM-1 antibody
a-MSH
Cell repair
IGF-1, EGF, HGF
IGF-1
Haemodynamic
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

Marimea catabolismului
Energy
substrates
AA/ protein
(g/Kg/day)
Nutrients
used
Mild
Moderate
Severe
glucose
glucose + fat
glucose + fat
0.6 - 0.8
EAA (+NEAA)
0.8 - 1.2
EAA + NEAA
1.0 + 1.5
EAA + NEAA
enteral
formulae
glucose
50 - 70 %
glucose
50 - 70%
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
Supravietuire: membrane
bio-incompatibile vs bio-compatibile
RCTs only
Cellulose-acetate
Cuprophane
Odds ratio
0.5
1.5
2.0
2.5
Subramanian et al, KI, 62, 1819-1823, 2002

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
% of nephrologists
% of ARF patients
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.
IHD Frequency (per week)
2000
Urea clearance (ml/hr)
Frecventa IHD necesara pt atingerea

controlului corespunzator al azotemiei la
pacientii cu IRA.
1000
0
50
60
70
80
90
100
6
5
4
3
2
50
Weight (Kg)
100 mg/dL
80 mg/dL
60 mg/dL
Clark et al, JASN, 8, 804-812, 1997.
60
70
80
90
Weight (Kg)
60 mg/dL
80 mg/dL
100 mg/dL
100
Efectul dozei de dializa asupra supravietuirii
% survival
100
75
50
high Kt/Vurea
25
0
CCF score outcome

low Kt/Vurea
6
8
10
12
14
CCF ICU ARF Score
16
18
Leblanc M, Paganini E Adv Ren Repl Ther 2: 255, 1995
20
Stabilitatea hemodinamica
p=NS
plasma concentration, % of t=0
Indepartarea citokinelor: studii clinice

150
TNF
IL-1b
IL-6
100
50
* p<0.05
0
12
18
24
Time (hours)
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
%
P= 0.02
P=0.02
N= 166
Prognosticul pe termen lung al

TSR la IRA in ATI
%
N=979
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)
CRRT
clasic
CVVHD cu volume mari

CVVHD
CVVH
CAVHD
CAVH
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.
P=NS
P=NS
P=NS
Kumar et al, AJKD, 36, 294-300, 2000
SLEDD: anticoagulare
No heparin: 31.9% in SLEDD vs 2.7% in CCVH (p<0,05)
Heparin need in units/day
Kumar et al, AJKD, 36, 294-300, 2000
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 )
Recomandari actuale de tratament in IRA

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
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

Acute Renal Failure

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Acute Renal Failure

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Acute Renal Failure

IRA si studentul la medicina

Definitia insuficientei renale acute

IMPORTANTA IRA (AKI)

IRA in ATI / reanimare

Limitele criteriilor RIFLE

Acute and Chronic Kidney Disease

Conceptual model for integration of AKI, CKD, and AKD.

Conceptual Model for AKI

KDIGO & AKI Guideline 2010

Definition and Staging of AKI

>1.5-1.9 times baseline

<0.5 ml/kg/h for 612 hours

>2.0-2.9 times baseline

<0.5 ml/kg/h for >12

>3.0 times baseline

<0.3 ml/kg/h for

Insuficienta renala acuta

Insuficienta renala acuta

72% erau varstnici > 70 ani

Beginning and Ending Supportive Therapy

JAMA. 2005 294(7):813-8.

Insuficienta renala acuta

Tipurile principale de IRA

Insuficienta renala acuta

Este IRA prerenala (functionala)

Necroza tubulara acuta 45%

Sdr de insuficienta renala acuta

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

Beginning and Ending Supportive Therapy

JAMA. 2005 294(7):813-8.

Evolutia mortalitatii in IRA vs IRC in Europa

Mortalitatea in primul an la pacientii cu BRC

Proportia de varstnici (> 80 ani) cu IRA

Akposso et al Intens Care Med 26:400-406,2000

Effect of acute renal failure requiring renal replacement

Blantz, KI, 53, 512-523, 1998.

Insuficienta renala acuta

Insuficienta renala acuta

Autoreglarea fluxului plasmatic renal

Flux sangvin renal relativ (%)

Presiune de perfuzie renala (mm Hg)

Insuficienta renala acuta

Riscul de IRA la AINS

Gutthann et al. Arch Int Med 156 2433-2439, 1996

Teoria hemodinamica (cont.)

Anatomical and physiologic features

Brezis & Seymour, The New Engl. J. of Med., 332,647-655, 1995.

Brezis et al, The Kidney, 1991.

Cortical Medullary Junction:

Crestere Ca2+ citosolic

Paller & Greene, Ann; Acad. Science, 723, 1994

Cell injury to hypoxic rat proximal is reduced by

Wetzels et al, J. Pharmacol. Exp. Ther., 267, 176, 1993

Pathways of formation of reactive

disparitia posibiltatii de vasodilatatie

Induction of tubular epithelial cell injury

Aspectul microscopic in NTA

Potential cytoskeletal targets for proteases