Contrast Induced Nephropathy Contrast Induced Nephropathy CIN - PDF document

Contrast Induced Nephropathy Contrast Induced Nephropathy • CIN increases morbidity, mortality and length of hospital stay Nabil Haddad, MD • Patients who developed a relative increase in serum creatinine of only 25 to 50% within The Ohio State University 3 days after cardiac catheterization had a 1.4 fold increase in odds for death, while Nephrology Division those who doubled their serum creatinine had a 3.6 fold increase in odds for death Contrast Induced CIN and Mortality Nephropathy • CIN is the development of acute renal failure after the administration of intravenous contrast • It is defined as an absolute increase in serum creatinine of ≥ 0.5 mg/dL or a relative increase of ≥ 25% above baseline within 2 to 7 days after contrast exposure • CIN is the third most common cause of hospital-acquired acute renal failure Weisbord et al; J Am Soc Nephr 2006 1

Risk Score for CIN Risk Factors for CIN after PCI Patient Related Risk Factor Points • Preexisting renal dysfunction with an estimated BP < 80 5 GFR of less than 60 mL/min or serum creatinine Points Risk for CIN IABP 5 of ≥ 1.5 mg/dL CHF 5 < 6 7.5% • Patients with DM Age > 75 4 • Hypovolemia 6-10 14% Anemia 3 DM 3 • Cardiovascular disease 11-16 26.1% Contrast Vol 1/100 ml • Intra-aortic balloon pump GFR 40-60 2 > 16 57.3% • Advanced age GFR 40-20 4 GFR < 20 6 • Exposure to nephrotoxins (NSAID, CSA) Mehran et al; J Am Coll Cardiol. 2004; 44: 1393–1399) Iodinated Contrast Risk Factors for CIN Agents Procedure Related • Ionic high-osmolar agents • High volume of contrast • Nonionic low-osmolar agents • Type of intravenous contrast – ionic vs • Nonionic iso-osmolar agent nonionic, iso-osmolar/low-osmolar vs high- osmolar � Iso-osmolar/low-osmolar agents are less nephrotoxic than high-osmolar • Multiple exposures to contrast agents agents 2

Pathogenesis Iodinated Contrast Agents Ionic Non-ionic Non-ionic Osmolality Name low-osmolar Contrast Agent Iso-osmolar (mosm/kg) Metrizoate + 2100 ↑ Endothelin/Adenosine Direct cytotoxic Increase (Isopaque) ↓ NO and Prostoglandines effect interstitial pressure Diatrizoate + 1530 (Hypaque) Decreased Ioxaglate + 580 Vasoconstriction renal blood flow (Hexabrix) Iopamidol + 616 ↓ Medullary (Isovue) Blood flow Iohexol + 640 (Omnipaque) Iodixanol + 290 ARF/Acute Tubular Necrosis (Visipaque) Risk of CIN in patients with and Drugs to hold prior to IV without renal insufficiency (RI) contrast administration and Diabetes (DM) • Metformin - ↑ risk of lactic acidosis 30 27 N=1196 • NSAIDS - ↑ risk of CIN 25 % of patients with CIN • Diuretics - ↑ risk of CIN 20 • Mannitol - ↑ risk of intravascular 15 volume contraction 11.8 10 7.4 Diatrizoate • Cyclosporin - ↑ risk of CIN 4.1 Iohexole 5 0 ACE inhibitors and ARB may be continued in stable RI(-) DM(-) RI (+) DM(-) RI(+)DM(+) patients on long term therapy Rudnick et al Kidney Int. 1995; 47: 254–261 3

Clinical Manifestations Clinical Manifestations • Incidence ranges from less than 2% in the • Urinalysis shows muddy brown casts general population to more than 50% typical for acute tubular necrosis depending on risk factors and various definitions • Differential diagnosis includes atheroembolic disease, interstitial • The risk is negligible with normal renal nephritis, different etiologies of acute function tubular necrosis including sepsis and other nephrotoxins, and prerenal acute kidney • Nephrotoxicity ranges from a nonoliguric injury transient mild renal failure to severe renal failure requiring hemodialysis Management of Contrast Clinical Manifestations Induced Nephropathy • In the majority of cases the renal failure is • The main issues are detection of risk factors mild and improves within 3 to 5 days and prevention • Persistent renal dysfunction may develop • Treatment is not effective in established CIN in some patients • Diuretics are used for volume control and do not expedite the recovery of renal function • End stage renal disease may develop especially in patients with advanced • Renal replacement therapy is required if renal chronic kidney disease and diabetes function worsens and/or volume status deteriorates 4

Strategies for Contrast Induced Prevention of CIN Nephropathy: Prevention 1. Volume Expansion 2. Bicarbonate Ganesh Shidham, MD 3. N-acetylcysteine Division of Nephrology 4. Choice of contrast agent The Ohio State University 5. Hemodialysis and Hemofiltration Prevention of CIN Outline Volume Expansion 40% 40 1. Strategies for prevention of CIN 35 28% % with CIN 30 2. Consensus panel recommendations 25 Saline + mannitol Saline + Mannitol 3. Algorithm for patients receiving contrast 20 Saline + Lasix Saline + Lasix 15 11% 10 Saline Saline 5 0 1 2 3 Solomon R et al. N Engl J Med 1994;331:1416-1420 5

Prevention of CIN Prevention of CIN Bicarbonate Volume expansion – Oral vs IV 34.6 35 30 Merten; JAMA 291; 2328-2334: 2004 25 % CIN 20 IV Bicarb saline onate 15 (n=59) (n=60) 10 CIN % 13.6 (8) 1.7 (1) 3.7 5 0 IV saline Oral Hydration Trivedi: Nephron Clinical Practice 93:29-34;2003 Prevention of CIN Prevention of CIN Bicarbonate ( REMEDIAL trial ) Volume Expansion Saline + NAC Bicarbonate + Saline + • IV fluid administration is superior to NAC Ascorbic acid + NAC oral hydration N=111 N=107 N=108 • Isotonic saline is superior to hypotonic fluid CIN 11 (9.9%) 2 (1.9%)* 10 (10.3%) p-0.019 • Both Lasix and Mannitol – increase the risk for CIN Relatively small study size . If 1 patient less in Saline group and 1 more patient in Bicarb group had developed CIN – results would be NS Briguori; Circulation 15:1211-1217, 2007 6

Prevention of CIN Prevention of CIN N-Acetylcysteine Bicarbonate (RENO trial) Group B: n=55 Group A: n=56 • Subject of numerous clinical trials and intense debate Post procedure IV Pre procedure Bicarbonate + NAC + Saline + NAC post procedure Saline • First study in NEJM 2000, Tepel CIN 1/56 (1.8%) 12/55 (21.8%) • Since then 25 RCT and 17 meta- analyses with conflicting results • Rates of fluid different in both groups • Difference in outcome could be due to difference of fluid given pre procedure rather than due to Bicarbonate Recio-Mayoral, J AM Coll Cardio 49:1283-1288, 2007 Prevention of CIN Prevention of CIN N-Acetylcysteine Bicarbonate • Insufficient Data to make firm recommendation for prevention of CIN Tepel, NEJM 2000 7

Prevention of CIN Prevention of CIN Intravenous N-Acetylcysteine N-Acetylcysteine Negative study • Despite large number of studies, literature is inadequate to resolve the question of NAC’s effectiveness at preventing CIN Bagshaw; Arch Int Med 166:161-166, 2006 Webb; Am Heart J 2004;148:422-9 Prevention of CIN Prevention of CIN N-Acetylcysteine Choice of Contrast Agent • Low-osmolar/Iso-osmolar contrast agents substantially decrease CIN in high risk patients as compared to * high-osmolar contrast agent • Low-osmolar vs Iso-osmolar ? *Limitation: Rate of CIN in control group significantly high Marenzi; NEJM 2006;354:2773-82 8

Prevention of CIN Prevention of CIN Choice of Contrast Agent Hemodialysis and Hemofiltration “NEPHRIC study” N=64 N=65 N=129 Iodixano l:Iso-osmolar Iohexol :Low-osmolar Aspelin; NEJM 2003 Cruz; Am J Kid Dis 2006 Differences in Nephrotoxicity between Iodixanol and Iohexol Prevention of CIN Prevention of CIN Hemofiltration- CVVH Choice of Contrast Agent General Consensus: • In high risk patients – an iso-osmolar or low-osmolar contrast agent should be used • Minimize volume of contrast agent • Avoid repetitive exposure to contrast in short period of time Marenzi; Am J Med 2006 9

Prevention of CIN Prevention of CIN Consensus Panel Hemodialysis and Recommendations Hemofiltration 1. All patients must be evaluated for CIN risk. Presence of multiple risk factors can create a risk of 50% for CIN and risk of 15% ARF requiring dialysis • Studies of Hemodialysis after contrast have suggested the potential for harm 2. All patients should be in optimal volume status. Intravenous Normal saline 1 to 1.5 ml/kg for 3 to 12 hrs before and 6 to 24 hr after the procedure. Data on • The relative risk for CIN associated oral fluid is insufficient with HD was 1.35 3. High risk patients considered for pharmacologic prophylaxis with therapies supported by clinical • Prophylactic CVVH not recommended evidence 4. Non ionic, iso-osmolar contrast medium is associated with lowest risk for CIN Prevention of CIN Prevention of CIN Consensus Panel Consensus Panel Recommendations Recommendations 5. Intra-arterial administration of contrast pose a greater risk than intravenous • Consensus Panel for CIN 6. High contrast volume associated with higher rates of CIN in patients at risk • CIN Consensus Working Panel 7. Drugs that adversely affect renal functions should be withheld 8. Follow up creatinine in 24-72 hrs after exposure 9. Prophylactic Hemodialysis and Hemofiltration have not been validated as effective 10