nefropatia da mezzo di contrasto Giuseppe Rombolà La Spezia

CIN (CI-AKI) Both clinical studies and ESUR definition (Thomsen H. Curr. Opin. Urol. 2007; 17: 70) Increase in serum creatinine (sCr) ≥ 0.5 mg/dL and/or ≥ 25% from baseline within 3 days of CM exposure And the absence of other causes (e.g. atheromatous embolic disease, ischemia, other nephrotoxins, etc.)

CIN (CI-AKI) definition Stage I AKIN definition Increase in sCr ≥ 0.3 mg/dL or ≥ 15 to 20 % from baseline (Metha R. Crit.Care 2007) CIN definition: sCr. Increase ≥0.3mg/dL Solomon R. Clin. JASN 2009 Mitchell A. Clin JASN 2010 Briguori C. Circulation 2010

Carico tubulare di Na e acqua Riassorbimento di Na e acqua Mezzo di contrasto DIURESI OSMOTICA Vasodilatazione Carico tubulare di Na e acqua Consumo di ossigeno IPOSSIA MIDOLLARE vasocostrizione CIN Apparato Juxtaglomerulare RAS Riassorbimento di Na e acqua nel TALH

7856 pts. after PCI Multivariate analysis RR Rihal C. Circulation 2002 493 pts. following CECT Multivariate analysis RR Lencioni R. Acta Radiol. 2010 Chronic Kidney Disease (scr. 2-2.9 mg/dl) 7.37 (4.7-11) Diabetes 1.61 (1.21-2.18) Congestive heart failure 1.53 (1.12-2.10) Periferal vascular disease 1.71 (1.23-2.37) Age 60 years: 1-Y increment 1.02 (1.01-1.03) CM dose (100 ml) 1,12 CONNECT STUDY

renal function deterioration after PCI and one year outcomes Mortality % % increase in serum creatinine <10 10-25 25-50 > 50 10 20 30 40 Gruberg et al. JACC 2000

Loss of kidney function and mortality after reversible CIN eGFR 36±7 ml/min/1.73m2 16±15 ml/min/1.73m2 31±15 ml/min/1.73m2 Goldenberg I. Am. J. Nephrol. 2009

CIN incidence following CM administration 50 45- 40 < 30 CIN incidence following CM administration gfr ml/min 2 V. in 4 studies (2008-2010) (diabetes 29-100 %) 3 V. in 1 study (2010) (diabetes 32%) A. in 5 RCT studies (2007-2009) (diabetes 28-100 %) A +CKD+ diabetes A + CKD only 115 1774 357 58 studies published before 2003 Mc Cullough, J. Cardiov. Med. 2003

Bicarbonato isotonico 1.4%: 90 Arteria volume di mdc …… 248 ± 112 ml 00 …… 122 ± 55 10 …… 117 ± 19 Infusione venosa < 100 ml Strategie preventive Espansione VEC (salina o bicarbonato) NAC Linee guida ESUR 1-1.5 ml/Kg/h 3-12 hrs pre e 12-24 hrs dopo mdc Bicarbonato isotonico 1.4%: 3 ml/kg/h: 1 hr pre e 1 ml/kg/h per 6 hrs dopo mdc

The NEPHRIC Study Although the role of osmolality in the development of CIN is not yet clearly established, clinical studies indicate that use of IOCM decreases the incidence of CIN in patients at high risk compared to a LOCM (iohexol).40 The first study to suggest that the IOCM, iodixanol, reduced the incidence of CIN compared to a LOCM (iohexol) was performed by Chalmers and Jackson in 1999. In this prospective, comparative study, SCr was measured before and after angiography in 124 consecutive inpatients with a SCr >150 µmol/L randomised to receive either iodixanol (IOCM) or iohexol (LOCM). The patient groups were comparable at baseline; 33% had diabetes and 25% had undergone renal transplant. Significantly fewer patients experienced a >10% rise in SCr with iodixanol compared with iohexol (P<0.05).39 Subsequently, a double-blind, randomised, multicentre study was undertaken to compare the use of iodixanol and iohexol in high-risk patients undergoing coronary angiography.40 Results of the NEPHRIC study will be presented in the following slides. Nephrotoxicity In High-Risk Patients A Double-Blind, Randomized, Multicenter Study of Iso-Osmolar and Low-Osmolar, Nonionic Contrast Media The NEPHRIC Study References: Chalmers N, Jackson RW. Comparison of iodixanol and iohexol in renal impairment. Br J Radiol. 1999;72:701-703. Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ; Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media Study Investigators. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003;348:491-499.

NEPHRIC: Primary Endpoint Mean Peak Increase in SCr Up to Day 3 0.6 CIN -creat. < 0.5 mg/dl- 3 % Iodixanol 26 % iohexol 0.55 0.5 0.4 Increase in SCr (mg/dL) 0.3 NEPHRIC: Primary Endpoint Mean Peak Increase in SCr Up to Day 3 0.2 The 2 groups of patients were similar with respect to demographic and baseline characteristics. While patients in the iohexol group had a longer mean duration of diabetes (ie, time from diagnosis), retrospective analysis showed that this was not a predictive factor for the development of CIN. Patients in both groups were similarly hydrated and received approximately the same volume of CM. The primary endpoint in this study was the peak increase in SCr between Day 0 (administration of CM) and Day 3. In the iodixanol group, the peak increase in SCr was 0.13 mg/dL at Day 3, compared with 0.55 mg/dL in the iohexol group (P=0.001) 0.13 0.1 Iodixanol (n=64) Iohexol (n=65) Adapted from Aspelin P et al. N Engl J Med. 2003;348:491-499. Reference: Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ; Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media Study Investigators. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003;348:491-499.

efficacia della NAC nella prevenzione della CIN N pazienti RR Birck Lancet 2003 805 0.43 (0.21 – 0.87) Kshirsagar JASN 2004 1538 efficace nel 33 % Nallamothu Am.J. Med.2004 2195 0.73 (0.52 – 1.0) Alonso Am.J. Kid. Dis. 2004 885 0.55 ( 0.34 – 0.91) Zagler Am. Heart J. 2006 1892 0.68 (0.46 – 1.01)

119 pts

MYTHOS Protocol Diuresi > 300 ml/h PROCEDURA 4 ore 30 min Infusione In 20% of pts additional furosemide (0.5 mg/Kg) was required i.v. furosemide (0.5 mg/kg) Volume urine 826±342 ml/hr 48 - 16 min 30 min PROCEDURA 4 ore Diuresi > 300 ml/h 250 ml i.v. saline Infusione continua di sol fisiol in volume uguale alla diuresi Controllo parametri ogni 30 min RenalGuard

Transcatheter Cardiovascular Therapeutics CIN 157 pts. baseline GFR 39 ± 10 ml/min. % P=0.028 P=0.03 P NS 25% -69% -80% -60% Controls RenalGuard 16% 10% Added the patient numbers at the top of each column 6% 5% 4% Elective procedures All patients NSTEMI Marenzi; TCT 2010 Transcatheter Cardiovascular Therapeutics 17

2003

PREVENZIONE CIN & EMOFILTRAZIONE Marenzi G. Am. J. Med. 2006

Am J Med 2001

CONCLUSIONI CIN è associata con un peggioramento della funzione renale che aumentando il rischio CV può aumentare la mortalità CIN sembra rappresentare un rischio indipendente di mortalità sia a breve che a lungo termine I trattamenti depurativi extracorporei sembrano promettenti nel ridurre questo rischio

giuseppe.rombola@asl5.liguria.it