Nefropatia inducida por medio de contraste 2015

Nefropatía Inducida por

Contraste 2015

Dr. Cristhian Mauricio Bueno LaraEspecialista en medicina interna – Universidad Autónoma de Bucaramanga

Fellow en Nefrología – Universidad del Valle

Medios de contraste

contrast-induced nephropathy: how it develops, how to prevent it. Cleveland clinic journal of

medicine. volume 73, number 1. January 2006

• Antes de 1980

• Alta osmolaridad (2000 mOsm/L)

• 1980

• baja osmolaridad (600 - 900

mOsm/L)

Medios de contraste



• En la actualidad

• Iso-osmolar (300 mOsm/L)

Medios de contraste

2003

Iso-osmolar Vs Baja osmolaridad

3% Vs 26%Valor P = 0.002

Nefropatía Inducida de ContrasteDefinición

Incremento en la creatinina sérica ≥ 0.5 mg/dL

o un aumento del 25% en relación al valor de

base 48 horas posterior al contraste.

KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplements (2012) 2,

4

Nefropatía Inducida de ContrasteDefinición

2010

Nefropatía Inducida de ContrasteEpidemiología

• El riesgo de NIC en ausencia de enfermedad renal es 1 a 2%.

• Con enfermedad renal preexistente puede aumentar hasta el 25%


4

Lesión renal aguda

Nefropatía por contraste

Muerte

Hemof33%

3% - 7%

7.1% - 35.7%

Nefropatía Inducida de ContrasteEpidemiología


4

Lesión renal aguda

Nefropatía por contraste

Terapia de reemplazo renal

Nefropatía Inducida de ContrasteFisiopatología

Contrast Medium–induced Nephrotoxicity: Which Pathway?. Radiology 2005; 235:752–755



• Respuesta hemodinámica “bifásica”

• Hipótesis de la isquemia.

• Modelos animales = Isquemia al detener el flujo sanguíneo renal por 120

minutos.

Efecto hemodinámico



• Vacuolización celular, inflamación intersticial, necrosis celular y

enzimuria.

Alteraciones bioquímica y

Toxicidad directa

Nefropatía Inducida de ContrasteFactores de riesgo



• Factor de riesgo mas importante.

• 60 % de los pacientes que realizan nefropatía inducida por contraste

tienen compromiso renal previo.

Disfunción renal

preexistente

Probabilidad de NIC = Creatinina sérica (mg/dL) x 10


2010 Diabetes Mellitus

6358Pacientes


Volumen del contraste

1989

Peso: 70 Kg

Creatinina: 2 mg/dL

Volumen permitido: 175 ml

Nefropatía Inducida de ContrasteValoración pre-test

2004


2004

Riesgo de nefropatia inducida

por contraste

Riesgo de requerimiento de

hemodialisis


Escala de riesgo de Mehran


2014


2014

67%Sensibilidad

76%Especificidad


2015

Edad≥ 75 años: 1 punto

Función ventricular < 40%: 1

punto

Creatinina sérica > 1.5 mg/dL: 2

puntos

Riesgo bajo 0 puntos: 0%

Riesgo moderado 1 punto: 5.10%

Riesgo alto ≥ 2 puntos: 19.4%


2015

Nefropatía Inducida de ContrastePrevención

Trang H. Au, PharmD, Anne Bruckner, PharmD, Syed M. Mohiuddin, MD, and Daniel E. Hilleman,

PharmD. The Prevention of Contrast-Induced Nephropathy. Annals of Pharmacotherapy 2014, Vol.

48(10) 1332–1342


Cristaloides

2013


Estatinas

Efficacy of Short-Term High-Dose Statin in PreventingContrast-Induced Nephropathy: A Meta-Analysis ofSeven Randomized Controlled Trials

Yongchuan Li. , Yawei Liu . , Lili Fu, Changlin Mei*, Bing Dai*

Division of Nephrology, Nephrology Institute of PLA, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

Abst ract

Background: A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathyhave been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess theeffectiveness of shor-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of thepotential benefits of statin therapy.

Methods: We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trialsdatabases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statintreatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2–5 days after contrastadministration and need for dialysis.

Results: Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall resultsbased on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significantreduction in risk of CIN (RR= 0.51, 95% CI 0.34–0.76, p = 0.001; I2= 0%). The incidence of acute renal failure requiring dialysiswas not significant different after the use of statin (RR= 0.33, 95% CI 0.05–2.10, p = 0.24; I2= 0%). The use of statin was notassociated with a significant decrease in the plasma C-reactive protein level (SMD 2 0.64, 95% CI: 2 1.57 to 0.29, P= 0.18,I2= 97%).

Conclusions: Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered inthe context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statinbased on current data. Considering the limitations of included studies, a large, well designed trial that incorporates theevaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to moreadequately assess the role for statin in CIN prevention.

Citat ion: Li Y, Liu Y, Fu L, Mei C, Dai B (2012) Efficacy of Short-Term High-Dose Statin in Preventing Contrast-Induced Nephropathy: A Meta-Analysis of SevenRandomized Controlled Trials. PLoS ONE 7(4): e34450. doi:10.1371/journal.pone.0034450

Editor: Nick Ashton, The University of Manchester, United Kingdom

Received December 9, 2011; Accept ed February 28, 2012; Published April 12, 2012

Copyright: ß 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by grants from the National Natural Science Foundation of China (30900692, 81000283, 30971368) and Shanghai LeadingAcademic Discipline Project (B902). The funders had no role in study design, data collection and analysis, decision to publish, or preparat ion of the manuscript.

Compet ing Interests: The authors have declared that no competing interests exist.

* E-mail: [email protected] (BD); [email protected] (CM)

. These authors contributed equally to this work.

Int roduct ion

Contrast-induced nephropathy (CIN), characterized by the

development of acute renal failure after exposure to radiocontrast,

is the third leading cause of hospital-acquired acute renal injury,

accounting for 11% of all cases [1]. It is defined as an increase in

baseline serum creatinine level of 25% or an absolute increase of

44 mmol/ L (0.5 mg/ dL). Although CIN is generally benign in

most instances, it is associated with lengthened hospital stays,

increased health care costs, and higher risk of death [2–4]. Several

strategies, including using iso-osmolar contrast, limiting the

amount of administered contrast media and volume expansion

have become well established methods for the prevention of CIN.

The pathophysiological mechanisms of CIN is not well known.

However, multiple studies have suggested that renal vasoconstric-

tion, oxidative stress, inflammation and direct tubular cell damage

by contrast media may play crucial important roles in the renal

injury process [5–8]. Statins, drugs primarily associated with low-

density lipoprotein cholesterol-lowering effects, have been shown

to possess pleiotropic effects that include enhancement of

endothelial nitric oxide production [9–11], anti-inflammatory

and antioxidative actions [12,13]. Therefore, statins are consid-

ered as promising candidate agents for the prevention of CIN.

A few studies focused on statin therapy as specific prophylactic

measuresof CIN have been published with conflicting results [14–

22]. In this meta-analysis of randomized controlled trials (RCTs),

we aimed to assess the effectiveness of short-term high-dose statin

treatment for the prevention of CIN and clinical outcomesand re-

evaluate of the potential benefits of statin therapy.

PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e34450

Ta

ble

1.

Chara

cterist

ics

of

incl

ud

ed

stud

ies.

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tho

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034450.t001

Statin Prevents Contrast-Induced Nephropathy

PLoSONE | www.plosone.org 2 April 2012 | Volume 7 | Issue 4 | e34450

Ta

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1.

Chara

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034450.t001


PLoSONE | www.plosone.org 2 April 2012 | Volume 7 | Issue 4 | e34450Table 1. Characteristics of included studies.

Author,

year Pat ients,nInclusion

criteria

Stat in

protocol Control

Contrast

type

Median

contrast

volume,mlHydrat ion

procedure

Stat in Control Stat in Control

Sang-Ho Jo

et al,2008

118 118 CAG.SCr$ 1.1 mg/dL or

CrCl# 60 mL/min

Simvastatin,40 mg every 12

hours, 1 day pre-procedure

and 1 day post-procedure

Placebo Iodixanol 173 191 Isotonic saline,1 mg/kg/hour for 12 h

before and 12 h after procedure

Anna Toso

et al,2009

152 152 CAG and/or PCI.

CrCl, 60 ml/min

Atorvastatin,80 mg/day 2 days

pre-procedure and 2 days post-

procedure+NAC,1200 mg bid

from 1 day before to 1 day

post-procedure

Placebo+NAC,

1200 mg bid from 1

day before to 1 day

post-procedure

Iodixanol 151 164 NS,1 ml/kg/hour for 12 h before and

after the procedure

Xinwei

et al,2009

113 115 PCI Simvastatin, 80 mg/day from

admission to the day before,

20 mg/day after procedure

Simvastatin, 20 mg/

day

from admission to

the end

Iodixanol for

CKD,iohexol for

others

227 240 NS, 1 ml/kg/hour for 6 to 12 hours

before and 12 hours after procedure

Zhou Xia

et al,2009

50 50 CAG or PCI Atorvastatin,80 mg/day before

for 1day,10 mg/day for 6days

after procedure

Atorvastatin, 10 mg/

day for 7 days

Iopamidol 119 113 1000 mL saline infusion, for 12 hours

before and 12 hours after intervention

Sadik Acikel

et al,2010

80 80 CAG.eGFR. 60 ml/min per

1.73 m2Atorvastatin,40 mg/day,3 days

pre-procedure and 2 days

post-procedure

Nothing Iohexol 105 103 Isotonic saline,1 ml/kg/hour starting 4 h

before and continuing until 24 h after

procedure

Hakan Ozhan

et al,2010

60 70 CAG.SCr# 1.5 mg/dl or

eGFR$ 70 ml/min per 1.73 m2Atorvastatin,80 mg 1 day

pre-procedure and 2 days

post-procedure+600 mg

NAC bid pre-procedure

600 mg NAC bid pre-

procedure

Iopamidol 97 93 1000 ml saline infusion during 6 h after

procedure

Giuseppe Patti

et al,2011

120 121 CAG and/or PCI.

SCr# 3 mg/dl

Atorvastatin,80 mg(12 hs

before)+40 mg(2 hs before),

40 mg for 2days after procedure

Placebe+40 mg

atorvastatin for 2days

after procedure

Iobitridol 209 213 For patients CrCl, 60 ml/min,1 ml/hour/

kg for 12 h before and 24 h after

intervention

Statin = statin-treated group(high-dose);Contro l = control group(low-dose or non-statin);CAG= coronary angiography;PCI = percutaneous coronary intervention;CrCl = creatinine clearance;Scr = serum creatinine;eGFR= estimated

glomerular filtration rate;NAC= N-acetylcysteine;NS= 0.9% sodium chloride.

doi:10.1371/journal.pone.0034450.t001

StatinPrevents

Contrast-Induced

Nephropathy

PLoSO

NE

|w

ww

.plosone.org2

April2012

|Volum

e7

|Issue

4|

e34450

2012


Estatinas

Efficacy of Short-Term High-Dose Statin in PreventingContrast-Induced Nephropathy: A Meta-Analysis ofSeven Randomized Controlled Trials

Yongchuan Li. , Yawei Liu . , Lili Fu, Changlin Mei*, Bing Dai*

Division of Nephrology, Nephrology Institute of PLA, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

Abst ract

Background: A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathyhave been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess theeffectiveness of shor-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of thepotential benefits of statin therapy.

Methods: We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trialsdatabases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statintreatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2–5 days after contrastadministration and need for dialysis.

Results: Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall resultsbased on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significantreduction in risk of CIN (RR= 0.51, 95% CI 0.34–0.76, p = 0.001; I2= 0%). The incidence of acute renal failure requiring dialysiswas not significant different after the use of statin (RR= 0.33, 95% CI 0.05–2.10, p = 0.24; I2= 0%). The use of statin was notassociated with a significant decrease in the plasma C-reactive protein level (SMD 2 0.64, 95% CI: 2 1.57 to 0.29, P= 0.18,I2= 97%).

Conclusions: Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered inthe context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statinbased on current data. Considering the limitations of included studies, a large, well designed trial that incorporates theevaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to moreadequately assess the role for statin in CIN prevention.

Citat ion: Li Y, Liu Y, Fu L, Mei C, Dai B (2012) Efficacy of Short-Term High-Dose Statin in Preventing Contrast-Induced Nephropathy: A Meta-Analysis of SevenRandomized Controlled Trials. PLoS ONE 7(4): e34450. doi:10.1371/journal.pone.0034450

Editor: Nick Ashton, The University of Manchester, United Kingdom

Received December 9, 2011; Accept ed February 28, 2012; Published April 12, 2012

Copyright: ß 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by grants from the National Natural Science Foundation of China (30900692, 81000283, 30971368) and Shanghai LeadingAcademic Discipline Project (B902). The funders had no role in study design, data collection and analysis, decision to publish, or preparat ion of the manuscript.

Compet ing Interests: The authors have declared that no competing interests exist.

* E-mail: [email protected] (BD); [email protected] (CM)

. These authors contributed equally to this work.

Int roduct ion

Contrast-induced nephropathy (CIN), characterized by the

development of acute renal failure after exposure to radiocontrast,

is the third leading cause of hospital-acquired acute renal injury,

accounting for 11% of all cases [1]. It is defined as an increase in

baseline serum creatinine level of 25% or an absolute increase of

44 mmol/ L (0.5 mg/ dL). Although CIN is generally benign in

most instances, it is associated with lengthened hospital stays,

increased health care costs, and higher risk of death [2–4]. Several

strategies, including using iso-osmolar contrast, limiting the

amount of administered contrast media and volume expansion

have become well established methods for the prevention of CIN.

The pathophysiological mechanisms of CIN is not well known.

However, multiple studies have suggested that renal vasoconstric-

tion, oxidative stress, inflammation and direct tubular cell damage

by contrast media may play crucial important roles in the renal

injury process [5–8]. Statins, drugs primarily associated with low-

density lipoprotein cholesterol-lowering effects, have been shown

to possess pleiotropic effects that include enhancement of

endothelial nitric oxide production [9–11], anti-inflammatory

and antioxidative actions [12,13]. Therefore, statins are consid-

ered as promising candidate agents for the prevention of CIN.

A few studies focused on statin therapy as specific prophylactic

measuresof CIN have been published with conflicting results [14–

22]. In this meta-analysis of randomized controlled trials (RCTs),

we aimed to assess the effectiveness of short-term high-dose statin

treatment for the prevention of CIN and clinical outcomesand re-

evaluate of the potential benefits of statin therapy.


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Statistical analysisDichotomous data (contrast-induced nephropathy and need for

dialysis) were analyzed using the risk ratio (RR) measure and its

95% confidence interval (CI). Moreover, heterogeneity across

trials was evaluated with I2 statistic, which defined as I2. 50%. If

heterogeneity existed, a random-effect model was used to assess

the overall estimate. Otherwise, a fixed-effect model was chosen.

We assessed for potential publication bias by using Begg funnel

plots of the natural log of the relative risk versus itsstandard error

[25]. To further detect and evaluate clinically significant

heterogeneity, we also a priori decided to perform several

subgroup analyses to identify potential differences in treatment

across the trials. Subgroup analysis was conducted based on renal

function in participants at baseline (with or without renal

impairment), the control group property (low dose of statin or

control), the addition of NAC (with or without NAC), and Jadad

study quality score (Jadad. 3 or Jadad# 3). All tests were two-

tailed and a P value less than 0.05 was regarded as significant in

this meta-analysis.

Results

Selected studies and characteristicsWe identified 322 potentially relevant citations from the initial

literature search. After independently reviewing the title and

abstract of all potential articles, 34 articles were considered of

interest and reviewed in full-text. Of these, 27 were excluded from

the meta-analysis (review articles, retrospective studies, prospective

obervational studies, irrelevant to our aim). Although the study

carried out by Acikel Sadik et al [20] did not provide data on the

incidence of CIN, we requested it by directly contacting the

author. Therefore, seven randomized controlled studies with a

total of 1,399 patients with undergoing radiocontrast-related

procedures were identified and analyzed [16–22]. Our search

strategy is outlined in Figure 1.

Table 1 and table 2 summarizes the characteristics of the

included studies. All of them had been reported since 2008. 693

subjects were assigned to short-term high-dose statin treatment

group and 706 subjects were assigned to short-term low-dose or

non-statin treatment group. The proportion of patients lost to

follow-up was less than 5% in all studies. CIN was defined

Figure 2. Forest plot of risk rat ios and 95% confidence intervals (CI) for the incidence of contrast induced nephropathy amongpat ients assigned to stat in therapy versus control.doi:10.1371/journal.pone.0034450.g002

Figure 3. Funnel plot with 95% confidence intervals (CI) to assess for evidence of publicat ion bias.doi:10.1371/journal.pone.0034450.g003



2012


Bicarbonato

2004

Protocolo bicarbonato:

154 meq de Bicarbonato + 846 cc de DAD al 5%

3 ml/Kg/hora 1 hora antes del medio de contraste

1 ml/Kg/hora 6 horas después del medio de contraste


Bicarbonato

2004


Bicarbonato

2010


N acetilcisteina

ACT InvestigatorsRandomized Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)

Coronary and Peripheral Vascular Angiography : Main Results From the Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing

ISSN: 1524-4539 Copyright © 2011 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online

72514Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX

doi: 10.1161/CIRCULATIONAHA.111.0389432011, 124:1250-1259: originally published online August 22, 2011Circulation

http://circ.ahajournals.org/content/124/11/1250

located on the World Wide Web at: The online version of this article, along with updated information and services, is

http://circ.ahajournals.org/content/suppl/2011/08/18/CIRCULATIONAHA.111.038943.DC1.htmlData Supplement (unedited) at:

http://www.lww.com/reprintsReprints: Information about reprints can be found online at

[email protected]. E-mail:

Fax:Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters

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2011

RR: 1.0IC 0.81 – 1.25


N acetilcisteina

2013


Terapias sin evidencia o contraindicadas

Manitol

Furosemida

Dopamina

Fenoldopam

Hemodiálisis o

Hemofiltración

Prostaglandinas

Calcio-antagonistas

Teofilina

Acido ascórbico

Sulfato de magnesio

N acetil cisteína

Nefropatía Inducida de ContrastePronóstico

Mortalidad

William F. Finn. The clinical and renal consequences of contrast-induced nephropathy. Nephrol Dial

Transplant (2006) 21 [Suppl 1]: i2–i10

Gracias

Nefropatia inducida por medio de contraste 2015

Health & Medicine

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