冠状动脉造影中肝脏功能和肾功能异常课件

Renal Function and Dysfunction in Coronary Arteriography,Peter A. McCullough, M.D., M.P.H., F.A.C.C., F.A.C.P. William Beaumont Hospital, Royal Oak, MI, USA,Renal Insufficiency: A Marker of Cardiovascular Mortality and Morbidity,Cardiac Disease,Renal Disease,Acute Renal Failure and Death in the Cardiac Patient,Myocardial Infarction, Heart Failure, Arrhythmias, and Cardiac Death in the Renal Patient,Cardiorenal Risk,There are two major outcomes of this intersection of disease states, we will focus on acute renal failure in this series. McCullough PA. Cardiorenal Risk: An Important Clinical Intersection. Rev Cardiovasc Med. 2002.,Major Causes of Acute Renal Failure in Cardiac Patients,1) Acute Contrast Nephropathy,2) Acute Renal Failure after Cardiopulmonary Bypass Procedures,56 Review Articles and Editorials Concerning Treatment,35 Randomized Controlled Treatment Trials,Radiocontrast Nephropathy,McCullough PA, Manley HJ. Prediction and Prevention of Contrast Nephropathy. J Interven Cardiol 2001;14(5):547-558.,No Currently Approved Agents for Prevention or Treatment of RCN,Frequency of Radiocontrast Nephropathy,The incidence depends on how it is defined,N=1826 consecutive patients undergoing PCI,McCullough PA, Am J Med 1997;103:386-375.,*Validated at 16.5% in 8,628 consecutive series at Washington Hospital Center, Iakovou, et al. Submitted to ACC for publication in 2002.,14.5%*,Radiocontrast Nephropathy (RCN),DEFINITION New onset or exacerbation of renal dysfunction after contrast administration absent other causes: increase by 25% or absolute of 0.5 mg/dL,from baseline serum creatinine,Occurs 24 to 48 hrs postcontrast exposure, with creatinine peaking 5 to 7 days later and normalizing within 7 to 10 days in most cases,Prediction of RCN and Dialysis after PCI,N=424 N=3695 N=7586,Independent risk factors: CrClDiabetesContrast Volume,Mean age = 65, 72 kg man,Data adapted from Berns AS, Kidney International, 1989, McCullough PA, Am J Med 1997;103:386-375, Rihal et al, Circulation, 2002;105:2259-2264,RCN,Dialysis,CrCl 30 ml/min 30-40% RCN Rate,Kidney Disease Outcome Quality Initiative (K/DOQI) Classification of Renal Function,Stage I,Mild Kidney Function,Moderate Kidney Function,Stage II,Stage III,Stage IV,Stage V,Severe Kidney Function,Kidney Failure ESRD,130 120 110 100 90 80 70 60 50 40 30 20 15 10 0,CKD Risk Factors/Damage with Preserved GFR,“Chronic Kidney Disease” (CKD),Kidney Function (Glomerular Filtration Rate) ml/min/1.73m2 Creatinine Clearance (CrCl) ml/min,Predictors of ARF after PCI Circulation. 2002;105:2259, April 22, 2002 Online,Predictors of Death Circulation. 2002;105:2259, April 22, 2002 Online,Outcomes,McCullough PA, Am J Med 1997;103:386-375.,N=1826 consecutive patients undergoing PCI P .00001 for all pairwise differences,Mortality of Acute In-Hospital Renal Failure,Author Setting N ARFD Mortality McCullough (AJM,1997) PTCA 3,695 0.5% 39% Levy (JAMA,1996) CAN 16,248 (n=183, ARF) 34% Douma (JASN, 1997) ICU - (n=238) 76% Rialp (Ren Fail,1996) ICU 1,087 20.2% 63.3% Chertow (Arch IM,1995) ICU - (n=132) 70.0% Joachimsson (JCAn,1989) CABG 5,181 1.4% 57% Andersson (ThCVS,1993) CABG 2,009 2.2% 44% Chertow (Circ,1997) CABG 43,642 1.1% 63.7%,Survival of those Requiring Dialysis after PCI,Dialysis-free,Dialysis-dependent,Median survival = 2.75 months 2-year survival rate = 18.8%,McCullough PA, Am J Med 1997;103:386-375.,Long-Term Impact of RCN RCN defined as 0.5 mg/dl rise in Cr,Rihal, et al. Circulation. 2002;105:2259, April 22, 2002 Online,Adjusted, long term outcomes in 7586 patients with and without acute renal failure after angioplasty, p 0.0001. Acute renal failure is defined as a 0.5 mg/dl rise in Cr after PCI. MI = myocardial infarction. ARF = acute renal failure.,RCN is a Marker for: Inflammation Oxidative Stress Endothelial Dysfunction Atherosclerotic Burden Increased thiols Yet to be discovered factors,Renal Complications and Costs Multicenter Study of Perioperative Ischemia Group,Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, Mangano DT. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. The Multicenter Study of Perioperative Ischemia Research Group. Ann Intern Med. 1998 Feb 1;128(3):194-203.,N = 2222 CABG Patients from 24 Centers,OUTCOMES OF THOSE REQUIRING DIALYSIS FOLLOWING PCI Gruberg, Mehran, Dangas, et al. American College of Cardiology. 2000;Poster:11291175. Anaheim, CA.,Days or % of Patients,n = 12,054,Chronic dialysis: $51,000/yr3 Transplantation: $18,000/yr3,Dialysis-requiring ARF $128,000 per QALY saved2,Inpatient expenses: $1,227/day1,1Department of Health and Human Services, HCFA, Healthcare Indicators, 3Q 1999. 2Hamel MB, Phillips RS, Davis RB, et al. Ann Intern Med. 1997;127(3):195202. 3Economic cost of ESRD and Medicare spending by modality in Excerpts from United States Renal Data System 1999 Annual Data Report. Am J Kid Dis. 1999;34:S124S139.,Pathogenesis of Radiocontrast Nephropathy,Pathogenesis of Contrast Nephropathy,Toxicity of Contrast to Cells Direct cellular toxicity (ionic concentration dependent) Tubular sluffing Thick ascending limb Tamm- Horsfall protein Renal Ischemic Effects of Contrast *Intrarenal vasoconstriction (endothelin, histamine, NO)* Ischemic tubular injury Additive Insults to Injury Atheroembolism Systemic Hypotension-induced renal blood flow,The outer juxtamedullary nephron is at the greatest risk for ischemia because of its limited perfusion. Susceptibility to injury is high when contrast exposure results in intrarenal constriction and shunting of blood flow from this zone.,BLOOD FLOW AND INTERSTITIAL OXYGEN CONTENT,REGIONAL DISTRIBUTION IN RENAL CORTEX AND MEDULLA,Extracts 80%,Extracts 18%,Aortic Debris Keeley EC, Grines CL. Scraping of aortic debris by coronary guiding catheters: a prospective evaluation of 1,000 cases J Am Coll Cardiol. 1998 Dec;32(7):1861-5.,Model,Direct Toxicity,Decreased GFR,Renal Vasoconstriction,Acute Renal Failure,Other Factors, Serum Cr Oligouria ATN Volume Overload Uremia Dialysis Outcomes,Selection of Patients,Preventive Measures,Supportive Care,Injury Substrate Result,Prevention of Radiocontrast Nephropathy,PREVIOUS ATTEMPTS AT PREVENTING RCN,EITHER NO BENEFIT OR CAUSE HARM dopamine1 mannitol2 furosemide2 atrial natriuretic peptide1 mixed endothelin antagonists3 calcium channel blockers4 Immediate hemodialysis post contrast,SOME BENEFIT saline2 non-ionic contrast media5 Continuous Veno-Venous Hemofiltrationpre and post contrast6 N-Acetylcysteine Fenoldopam,1Weisberg LS, Kurnik PB, Kurnik BR. Kidney Int. 1994;45(1):259265. 2Solomon R, Werner C, Mann D, et al N Engl J Med. 1994;331(21):14161420. 3Wang A, Bashore T, Holcslaw T, et al American Society of Nephrology. Philadelphia, PA, 1998:137A. 4Carraro M, Mancini W, Artero M, et al. Nephrol Dial Transplant. 1996;11(3):444448. 5NEPHRIC Trial, NEJM, 2003.6Marenzi G, et. Al, TCT 2001, A292.,9.7,6.6,19.7,45.9,16.2,0,0,5.4,8.1,21.6,41,19.7,0,5,10,15,20,25,30,35,40,45,50,1,2,3,4,5,Any,Renal failure outcome by definition,Cases (%),Low UFR (150 mL/hr),High UFR (150 mL/hr),1 indicates 25% rise in serum creatinine; 2 indicates 50% rise in serum creatinine; 3 indicates 100% rise in serum creatinine; 4 indicates 1.0 mg/dL rise in serum creatinine; 5 indicates a peak creatinine of 5.0 mg/dL at 48 h or dialysis. UFR = urine flow rate,Stevens et al. (1999),Hydration and urine output after PCI is important,Regression 95% CI,r = -0.36, F = 5.73, p = 0.005 Urine Flow Rate (mL/hr), beta = -0.36, t = -3.33, p = 0.001 Baseline CrCl (mL/min), beta = 0.10, t = 0.93, p = 0.36,Urine flow rate (mL/hr),Change in Cr from baseline (mg/dL),1.5,0.5,0.5,1.5,2.5,3.5,4.5,0,60,120,180,240,300,Regression of induced urine flow rate predicting resultant change in serum creatinine,Stevens et al. (1999),Iodixanol (Visipaque) NEPHRIC Study, N Engl J Med 2003,Iodinated contrast choices*,Ionic High-osmolar 1500 mOsm: Iatrizoate (Hypaque Urografin) Iothalamate (Conray) Low-osmolar 600 mOsm: Ioxaglate (Hexabrix) Non-ionic, low-osmolar 600700 mOsm Iohexol (Omnipaque) Iopamidol (Isovue) Ioversol (Optiray) Non-ionic, iso-osmolar, 290 mOsm,More thrombogenic,More renal toxic More allergenic,*All have iodine concentrations of 280370 mg/mL,Less renal toxic Less allergenic,Less thrombogenic,Desirable to limit contrast to 100 mL,Ritchie (1993),ANTIOXIDANT THERAPY AND CONTRAST ASSOCIATED RENAL FAILURE,N-ACETYLCYSTEINE (NAC) THERAPY HAS BEEN DEMONSTRATED TO HAVE THE FOLLOWING RENAL EFFECTS: Increased renal blood flow during endotoxic shock Rejuvenates glutathione Scavenges oxygen free radicals Blocks mesangial VCAM and NF-k expression,NAC Meta-Analysis N=7 RCTs, 805 Subjects,Lancet 2003; 362: 598603,NAC randomised, 12 controlled trials,Fishbane et al. (2003),Study,NAC,Control,OR (random),Weight,OR (random),or sub-category,n/N,n/N,95% C.I.,%,95% C.I.,Tepel et al,1/41,9/42,5.78,0.09,(0.01, 0.76),Shyu et al,2/60,15/61,8.28,0.11,(0.02, 0.49),Diaz-Sandoval et al,2/25,13/29,7.81,0.11,(0.02, 0.54),Kay et al,4/102,12/98,10.25,0.29,(0.09, 0.94),Brigouri et al,6/92,10/91,10.92,0.57,(0.20, 1.63),Allaquaband et al,8/45,6/40,10.32,1.23,(0.39, 3.89),Durham et al,10/38,9/41,11.07,1.27,(0.45, 3.57),Oldemeyer et al,4/49,3/47,8.14,1.30,(0.28, 6.16),Goldenberg et al,4/41,3/39,8.08,1.30,(0.27, 6.21),Loutriakis et al,6/24,3/23,8.28,2.22,(0.48, 10.21),Vallero et al,2/12,0/8,3.25,4.05,(0.17, 96.19),Total (95% C.I.),570,558,100.00,0.54,(0.29, 1.03),Total events: 51 (NAC), 91 (Control),Test for heterogeneity: p = 0.008,Test for overall effect: Z = 1.86 (p = 0.06),0.01,100,0.1,Favours treatment,Favours control,1,10,Baker et al,2/41,8/39,7.81,0.20,(0.04, 1.00),The CONTRAST Trial: Algorithm,315 patients at 28 U.S. centers undergoing invasive cardiac procedure with calc