Contrast Induced Nephropathy

O CIAKI refers to an abrupt deterioration in renal function associated with the administration of iodinated contrast media O CIAKI is characterized by an acute (within 48 hours) 0.3 mg/dl or 50% increase in baseline SCr, or a reduction in urine output to <0.5 ml/kg per hour for more than 6 hours (Acute Kidney Injury Network) Journal of Nephrology 2010; 23(04): 387-398

O A more common definition is 0.5 mg/dl or 25% increase in baseline SCr within 3 days of intravascular CM exposure, in the absence of an alternative etiology O The SCr increase peaks between days 3 and 5 with levels usually returning to baseline within 1 to 3 weeks

Increasing risk O Technological advances in imaging modalities, expanding imaging application cardiology patients undergoing invasive coronary angiography and/or PCI Interventional radiology patients undergoing different procedures patients from a variety of different specialties undergoing diagnostic CT O And an aging world population Journal of Nephrology 2010; 23(04): 387-398

Associated with O increased morbidity and mortality O longer hospital stays O higher rates of in-hospital events; O higher rates of in-hospital 1-year and 5-year mortality Journal of Nephrology 2010; 23(04): 387-398

Risk factors O CKD particularly CKD combined with diabetes mellitus DM O Advanced age O Metabolic syndrome O Prediabetes O Hyperuricemia O Hypertriglyceridemia O Impaired fasting glucose O Gender (women 65 years of age are at greater risk than their male counterparts) O Intra-arterial contrast administration Journal of Nephrology 2010; 23(04): 387-398

Pathogenesis

O Contrast media causes direct injury to the cells lining the renal tubule O The injury can be reproduced in vitro by incubating cells of the proximal tubule with contrast media O Cell death begins within minutes of exposure O The contrast media is taken up into the cells and alters mitochondrial function resulting in generation of reactive oxygen species and apoptosis Radiologic Clinics of North America Volume 47, Issue 5, September 2009

O This injury is exacerbated by a simultaneous reduction in medullary blood flow that occurs in vivo resulting from vasoconstriction of the vasa recta O The medulla of the kidney has both very high oxygen consumption supporting active sodium transport and low tissue oxygen levels O Critical tissue hypoxia results following contrast media leading to additional damage of tubule cells within this region of the kidney Radiologic Clinics of North America Volume 47, Issue 5, September 2009

Investigative Radiology Volume 45, Number 4, April 2010

Incidence

The American Journal of Cardiology Volume 98, 18 September 2006

Incidence in outpatients O O O O O A prospective, consecutive cohort (June 2007 through January 2009) of patients who received intravenous contrast for CECT in the emergency department of a large, academic, tertiary care center was enrolled The incidence of CIN was 11% (70 of 633) among the 633 patients enrolled Fifteen (2%) patients died within 45 d, including six deaths after study-defined CIN Seven (1%) patients developed severe renal failure, six of whom had study-defined CIN Of the six patients with CIN and severe renal failure, four died, and adjudicators determined that renal failure significantly contributed to all four deaths. Mitchell et al. CJASN January 2010 Vol 5

ACE inh and ARB O Four hundred twelve patients were included in a prospective, single-center study (January 2001 July 2004) to compare different treatments for CIN prevention O Creatinine levels within 72 h after CM application and in-hospital outcomes were documented Kiski D et al. Nephrol. Dial. Transplant. 2010;25:759-764

Kiski D et al. Nephrol. Dial. Transplant. 2010;25:759-764

Prevention

Contrast media Type of contrast

CONTRAST EXPOSURE Increased Viscosity Depends on Monomer vs Dimer forms Direct Vasoconstriction ISCHEMIA Increased Adenosine DIRECT CELLULAR TOXICITY Free Radical Formation Mitochondrial Toxicity Depends on Ionization Cell Vacuolization Depends on Osmolarity

Osmolarity Davidson et al (2006) Am J Cardiol 98(supp 6):42-58

Circulation: Cardiovascular Interventions. 3(4):351-358, August 2010.

Circulation: Cardiovascular Interventions. 3(4):351-358, August 2010

Contrast Media Dose of contrast

O Consecutive patients undergoing PCI were prospectively enrolled in the Dartmouth Dynamic Registry from 2000 to 2008 (n=10065) O Patients with preexisting dialysis-dependent renal failure were excluded (n=155) O Maximal acceptable contrast dose (MACD) was defined as (5 ml body weight [kg])/baseline serum creatinine [mg/dl] Circulation: Cardiovascular Interventions Volume 3(4), August 2010

Final model included age, sex, body surface area, diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, priority of PCI, number of stents inserted, and baseline estimated glomerular filtration rate using MDRD equation Circulation: Cardiovascular Interventions Volume 3(4), August 2010

CONTRAST EXPOSURE Increased Viscosity Pre-Hydration Direct Vasoconstriction ISCHEMIA Increased Adenosine -Theophylline Mitochondrial Toxicity -Dialysis DIRECT CELLULAR TOXICITY Cell Vacuolization Free Radical Formation -N Acetyl Cysteine -Bicarbonate

Volume expansion

Group 1 subjects (n = 27) received 0.9% saline for 24 h at a rate of 1 ml/kg/h beginning 12 h prior to scheduled catheterization; and group 2 subjects (n = 27) were allowed unrestricted oral fluids Nephron Clin Pract. 2003;93:C29 C34

A total of 1620 patients scheduled for elective or emergency coronary angioplasty were randomly assigned to receive isotonic (0.9% saline) (n = 809) or half-isotonic (0.45% sodium chloride plus 5% glucose) (n = 811) hydration beginning the morning of the procedure for elective interventions and immediately before emergency interventions. IV fluids were started at a rate of 1 ml/kg of body weight per hour at 8 AM on the day of coronary angioplasty or immediately on arrival in the catheter laboratory in case of emergency procedures. After the procedure, hydration was continued at 1 ml/kg of body weight per hour until 8 AM the next morning. Arch Intern Med. 2002;162:329-336

Bicarbonate

Zoungas S et al. Ann Intern Med 2009;151:631-638

N Acetylcysteine

Kelly A M et al. Ann Intern Med 2008;148:284-294

O 354 consecutive patients undergoing primary angioplasty were randomized to one of three groups: 116 patients were assigned to a standard dose of N-acetylcysteine (a 600-mg intravenous bolus before primary angioplasty and 600 mg orally twice daily for the 48 hours after angioplasty) 119 patients to a double dose of N-acetylcysteine (a 1200-mg intravenous bolus and 1200 mg orally twice daily for the 48 hours after intervention) 119 patients to placebo N Engl J Med 2006; 354:2773-2782

O In a study presented at the American Heart Association's annual meeting 2,308 patients undergoing an angiographic procedure were randomized to 1,200 mg of N-acetylcysteine, prescribed orally twice daily, with two doses given before the procedure and two doses after the procedure, or to placebo O There was no difference in the primary end point of contrast-induced nephropathy and no difference in the secondary end point of serum creatinine elevations

Renal Replacement Therapy

O It has been shown that dialysis removes contrast O However earlier trials have not been able to show any benefit to dialyze patients after administration of contrast O Dialysis was attempted at different times 1, 1.8 and 2 hours after contrast administration and in one study it was performed during the procedure itself O Some of those trials even showed worse kidney outcomes with dialysis

Dialysis Group (n = 42) Control Group (n = 40) p Value Age (yrs) 65.3 ± 11.1 65.9 ± 11.2 0.780 Male 27 (64%) 26 (65%) 0.946 Body weight (kg) 63.7 ± 10.2 61.0 ± 10.0 0.220 Systemic hypertension 40 (95%) 37 (93%) 0.604 Diabetes mellitus 23 (55%) 25 (62%) 0.477 Coronary artery disease 0.600 Stenosis <50% 3(7%) 1(3%) Single-vessel 16 (38%) 12 (30%) Double-vessel 8(19%) 10 (25%) Triple-vessel 15 (36%) 17 (42%) Prior myocardial infarction 10 (24%) 7(18%) 0.481 Left ventricular ejection fraction 0.45±0.07 0.42±0.08 0.221 Use of ACE inhibitors 11 (26%) 11 (28%) 0.894 Indication for CAG 0.812 Stable angina 22 (52%) 22 (53%) Acute coronary syndrome 20 (48%) 18 (47%) Performed procedure 0.837 Coronary angiography 19 (45%) 19 (47%) Percutaneous coronary intervention 22 (55%) 21 (53%) Volume of contrast medium (ml) 106.8 ± 44.0 108.1 ± 32.6 0.877 Journal of the American College of Cardiology Volume 50, Issue 11, 11 September 2007

O All patients were given intravenous normal saline at 1 ml/kg/h for 6 h before and 12 h after contrast medium exposure, and then randomized to receive hemodialysis (dialysis group) or not (control group) O In the dialysis group, dialysis was started as soon as technically possible after angiography, and the time interval from contrast exposure to initiation of dialysis was recorded O The duration of dialysis was 4 h O To lessen the hemodynamic changes, 200 ml normal saline priming was administered before dialysis and no fluid removal was prescribed in the dialysis group Journal of the American College of Cardiology Volume 50, Issue 11, 11 September 2007

Changes from baseline in the Cr level were significant at the peak value in the dialysis group (***p = 0.008) and on day 4, at the peak value, and at discharge in the control group (*p < 0.001); the difference between the 2 groups was significant on day 4 and at peak value (**p = 0.010 on day 4; p = 0.005 at peak value) Journal of the American College of Cardiology Volume 50, Issue 11, 11 September 2007

Journal of the American College of Cardiology Volume 50, Issue 11, 11 September 2007

Marenzi et al. N Engl J Med. 2003 Oct 2;349

O O O O Patients were assigned to receive either hemofiltration therapy in ICU (hemofiltration group) or intravenous hydration with isotonic saline given in a step-down unit (control group) For patients in the hemofiltration group, a treatment session was started 4 to 6 hours before the scheduled coronary procedure; treatment was resumed after the procedure was completed and continued for 18 to 24 hours The flow of isotonic replacement fluid was set at a rate of 1000 ml per hour and was exactly matched with the rate of ultrafiltrate production, so that no net fluid loss resulted Patients in the control group received a continuous intravenous infusion of isotonic saline at a rate of 1 ml per kilogram of body weight per hour for 6 to 8 hours before and 24 hours after the coronary procedure Marenzi et al. N Engl J Med. 2003 Oct 2;349

Temporary renalreplacement therapy was required in 25 % of the control patients and in 3 % of the patients in the hemofiltration group The rate of in-hospital events was 9 % in the hemofiltration group and 52% in the control group (P<0.001) In-hospital mortality was 2% in the hemofiltration group and 14% in the control group (P=0.02) The cumulative one-year mortality was 10 % and 30%, respectively (P=0.01) Marenzi et al. N Engl J Med. 2003 Oct 2;349

Controls (n = 30) Post-hemofiltration (n = 31) Pre/post hemofiltration (n = 31) P value Age (y) 71±6 72±8 72±7.86 Men 22 (73%) 23 (74%) 20 (65%).65 Weight (kg) 71±8 73±9 68±7.12 Diabetes 12 (40%) 9(29%) 7(23%).86 Hypertension 18 (60%) 21 (68%) 23 (74%).50 Prior MI 8(27%) 13 (42%) 10 (32%).44 Prior CABG 3(10%) 5(16%) 4(13%).77 Prior PCI 2(7%) 2(6%) 1(3%).80 Prior CHF 5(17%) 9(29%) 6(19%).47 Mean LVEF (%) 47±10 46±12 48±12.66 LVEF < 40% 9(30%) 12 (39%) 8(26%).24 Peripheral arterial disease 9(30%) 9(29%) 10 (32%).96 Cerebral vascular disease 4(13%) 4(13%) 5(16%).92 COPD 5(17%) 4(13%) 4(13%).89 Chronic atrial fibrillation 4(13%) 3(10%) 2(6%).66 Aspirin 15 (50%) 19 (61%) 13 (42%).31 ACE inhibitor or ARB 9(30%) 10 (32%) 8(26%).85 Diuretics 17 (57%) 20 (64%) 18 (58%).80 Indication for angiography Stable angina 10 (33%) 8(26%) 9(29%).81 Recent MI 4(13%) 7(23%) 6(19%).64 Unstable angina 9(30%) 10 (32%) 8(26%).85 Other 7(23%) 6(19%) 7(23%).92 Serum creatinine (mg/dl) 3.6±0.8 3.6±0.7 3.7±0.9.85 Creatinine clearance (ml/min) 20±5 20±4 18±4.12 Marenzi et al. Am J Med. 2006 Feb;119(2)

Patients were randomized in a 1:1:1 ratio to receive 1 of the following 3 prophylactic treatments: intravenous hydration with isotonic saline, performed for 12 hours before and for 12 hours after contrast agent exposure (control group) intravenous hydration with isotonic saline, performed for 12 hours before contrast agent administration, followed by hemofiltration treatment for 18 to 24 hours after contrast agent exposure (post-hemofiltration group) hemofiltration treatment performed for 6 hours before and for 18 to 24 hours after contrast agent exposure (pre/post-hemofiltration group)

Marenzi et al. Am J Med. 2006 Feb;119(2)

Controls (n = 30) Post hemofiltration (n = 31) Pre/post hemofiltration (n = 31) Acute myocardial infarction 5(17%) 4(13%) 1(3%).21 Emergency CABG 0(0%) 0(0%) 0(0%) - p value Pulmonary edema requiring MV Cardiogenic shock requiring IABP 1(3%) 1(3%) 0(0%).59 1(3%) 0(0%) 0(0%).35 Blood transfusion 4(13%) 6(19%) 5(16%).81 ARF requiring RRT 9(30%) 3(10%) 0(0%).002 2 clinical complications In-hospital mortality 6(20%) 2(6%) 0(0%).019 6(20%) 3(10%) 0(0%).02 Marenzi et al. Am J Med. 2006 Feb;119(2)

Weisbord, ASN renal week, Denver, Co November 2010