Contrast Nephropathy AKI

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A ppt about contrast nephropathy: basics, risk factors, comparison of preventive strategies. critical review of POSEIDON trial and brief about PRESERVE trial.

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  • 1. Presenter : Manish Kumar Singla Clinical Nephrology and transplant fellow University of Toronto Moderator : Dr Ron Wald June 17th 2014

2. It is one of the common causes of AKI hospitalized patients. CI-AKI was reported to be the third most common cause of AKI in hospitalized patients. Nash et al. AJKD 2002;39:930-6. Reported incidence varies from 1.7-2% of patients without predisposing factors and up to 10-45% of patients with predisposing factors. 3. Definition: New onset acute kidney injury (absolute Cr rise 0.5 mg- 1 mg/dl or relative, 25%-50% from baseline) after contrast administration and in the absence of other etiology Time course of CI-AKI: Occurs after 24-48 hrs of contrast Cr peaks in 3-5days and normalizes in 7-10 days(70%) In 30%, 3 weeks to return baseline or progress to CKD Predominantly non-oliguric AKI and with mild proteinuria 4. Patient-related Renal insufficiency Diabetes mellitus* Intravascular volume depletion Reduced cardiac output Concomitant nephrotoxins Procedure-related volume of radiocontrast Multiple procedures w/i 72 hours Intra-arterial administration Type of radiocontrast } * Diabetes alone not strong risk factor additive risk 5. Class Agents Osmolality (msom) Osmolality (compared to plasma) High- osmolar Ionic monomers Iothalamate (conray) Diatrizoate (hypaque) Metrizoate 1400-2000 5-8 Low- osmolar Non-ionic monomers Iohexol (omnipaque) Ioversol (optiray) Iopamidol Iopromide 600-800 2-3 Ionic dimer Ioglaxate Iso- osmolar Nonionic dimer Iodixanol(visipaqu e) Iotrolan 300 1 6. Left ventricular &-----: 30-45 mL aortic angiography PCI-----------------------:150-200 mL CECT scan--------------:uses 100-150 mL IVU-----------------------:100-mL bolus of a 50%60% FFA uses Na fluorescein and not assoc with CIN 7. 0 20 40 60 80 100 120 0 1 2 3 4 number of risk factors Arch Intern Med 1990;150 8. How contrast agents cause AKI ? 9. Contrast Induced AKI Direct tubular toxicity Oxidative stress 10. A temporary increase in renal transport work in the thick ascending limb of Henle's loop ( in oxygen consumption) + Constriction of medullary capillaries ( in medullary oxygen delivery) LEAD TO MEDULLARY ANGINA Solomon, et al. Kidney Int 1998; 230-242 11. Radiocontrast Administration CIN Medullary Hypoxia Generation of ROS Intrarenal Vasoconstriction Direct Cytotoxicity Rheologic Effects Osmotic Load 12. Universally iatrogenic Risk factors well characterised Time of insult largely predictable Make it amenable to prevention 13. CCB Loop diuretics* Mannitol* Dopamine* Fenoldopam* ANP Hemodialysis* NAC Theophylline Aminophylline Ascorbic acid Statins Hemofiltration IVF Ineffective EffectiveUnclear benefit * Possibly harmful 14. HEMODIALYSIS: Contrast medium is dialyzable and there were initial reports that HD was beneficial in preventing CIAKI. Later studies showed that in patients not previously on RRT, HD had no preventive role even if given within 1 hr of procedure and one study even reports a detrimental effect. 15. Tepel M, et al. N Engl J Med 2000; 343:180-184 0% 5% 10% 15% 20% 25% %CIN(Scr0.5mg/dL@48h) Control 2% 21% P=0.01 NAC 16. Publication of this study was followed by a proliferation of clinical trials evaluating NAC 17. most NAC trials enrolled small numbers of patients on the basis of large postulated effect sizes, used small changes in kidney function as the primary endpoint, and did not systematically track longer-term sequelae of CI-AKI. The inconclusive and contradictory results of these trials also led to multiple meta- analyses with conflicting conclusions 18. Meta-analysis 19. Citing these results, 2011 guidelines issued by the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions state that NAC is not useful for the prevention of CI-AKI and recommend against its administration 20. Protective effect unclear Many studies to date have methodological flaws Cheap and benign (in oral form) Should not be used in lieu of other measures 21. 1994 present Provide clinical basis for: Protective effect of IVF Deleterious effect of furosemide Superiority of isotonic IVF Superiority of IVF to pt-directed oral fluids Potential benefit of oral NaCl 22. Rate of CIN: 11% 28% 40% Solomon R, Werner C, Mann D, DElia J, Silva P. N Engl J Med. 1994;331:1416-1420. 23. Mueller C, et al. Arch Int Med. 2002; 162:329-336 P=0.04 P=0.35 P=0.93 24. 13.6% 1.7% 0% 2% 4% 6% 8% 10% 12% 14% NaCl (n=59) NaHCO3 (n=60) rate of CIN (8/59) (1/60) Merten et al. JAMA 2004;291:2328-2334 P = 0.02 25. Presumed effect size -67%, allowed the study with small sample size of 260. (33% would have needed 1300 Switch of one patient would have resulted in statistically negative study 26. 1. Although the summary of the published data favours bicarbonate but this is due the effect of the smaller, poorer quality trials . 27. Clin J Am Soc Nephrol 4: 15841592, 20 Trials those who included patients with CKD2-4 as well as normal renal function. 28. Power curve: the relationship between trial size and power. Hiremath S , and Brar S S Nephrol. Dial. Transplant. 2010;ndt.gfq279 The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org 29. 1. This metanalysis highlights that the perceived benefit of sodium bicarbonate is largely driven by small, underpowered RCTs with extreme treatment effects and wide CIs. 2. Among the large randomized trials there was no evidence of benefit for hydration with NaHCO3 compared with NaCl for the prevention of CI-AKI. ------CLINICAL EQUIPOISE-------- Clin J Am Soc Nephrol 4: 15841592, 20 Trials those who included patients with CKD2-4 as well as normal renal function. 30. NAC of unclear benefit Can use 1200 mg po bid x 2 days IV fluids beneficial isotonic >> hypotonic ? Superiority of NaHCO3 Abbreviated regimen OK 1 hr pre and 4-6 hr post 31. Dal lake, Kashmir, India 32. Volume? Duration ? Very little is known about the optimal rate and duration of fluid administration around the time of contrast exposure. So far, no trial has directly compared volume expansion with isotonic saline at different rates or durations in at risk populations Not unexpectedly, these uncertainties might explain, in part, the non-uniform adoption of volume expansion strategies. POSEIDON Trial 33. Poseidon is one of the twelve Olympian deities of the pantheon in Greek mythology. His main domain is the ocean, and he is called the "God of the Sea". Additionally, he is referred to as "Earth-Shaker due to his role in causing earthquakes, and has been called the "tamer of horses 34. Aimed to investigative different rates of fluid administration guided by the left ventricular end-diastolic pressure 35. Between Oct 10, 2010, and July 17, 2012, All consecutive patients referred to the cardiac catheterization laboratory at the Kaiser Permanente Medical Center in Los Angeles, CA, USA Funded by Kaiser Permanente Southern California regional research committee grant 36. eGFR of 60 mL/min or lower age 18 years or older and at least one of the following: diabetes mellitus history of congestive heart failure hypertension age older than 75 years 37. inability to obtain consent from participants emergency cardiac catheterisation Renal replacement therapy exposure to radiographic contrast media within the previous 2 days allergy to radiographic contrast media acute decompensated heart failure severe valvular heart disease mechanical aortic prosthesis left ventricular thrombus history of kidney or heart transplantation change in estimated GFR of 7.5% or more per day or a cumulative change of 15% or more during the preceding 2 or more days 38. Eligible patients randomized in a 1:1 ratio to either left ventricular end-diastolic pressure- guided therapy or a standard fluid administration protocol Randomization was stratified by diabetes mellitus status and N-acetylcysteine use. This study was partly blinded 39. Creatinine was measured at baseline and twice afterward between day 1 and 4. Commercially available 0.9% sodium chloride used in all patients A bolus infusion at 3 mL/kg for 1 h was given to all patients before the procedure 40. Before the administration of contrast media, LVEDP was measured by placing an angled 5 or 6-French pigtail catheter in the mid-cavity of the left ventricle. Fluid rate was adjusted according to the LVEDP as follows: 5 mL/kg/h for LVEDP lower than 13 mm Hg, 3 mL/kg/h for LVEDP of 1318 mm Hg, and 1.5 mL/kg/h for LVEDP higher than 18 mm Hg. The control group was hydrated at 1.5 mL/kg per h. Infusion was continued for the duration of the procedure, and for 4 h post-procedure in both groups 41. Primary outcome Primary endpoint was increase in the serum creatinine of greater than 25% or 0.5 mg/dL from baseline Secondary endpoints components of the primary endpoint occurrence of major adverse events at 30 days and 6 months :- composite of all- cause mortality myocardial infarction or renal replacement therapy 42. Analyses were done with Stata version 12.0 and R version 2.15.3. All tests were two-tailed, with differences reported as significant if the p value was less than 0.05 43. total mean (SD) volume of NS administered was 1727 ml in LVEDP group vs 812 ml in control group 44. Overall incidence of CI AKI was 11.4% - it was 6.7 % in LVEDP group vs 16.3% in control group (p = 0.005) Relative risk was 0.41 (95% CI 0.220.79) NNT 11 45. Patients who received larger volumes of normal saline had a lower rate of contrast-induced acute kidney injury than did those given smaller volumes Among patients with LVEDP > 18, incidence of CI AKI was 5.3% (8/152) in the treatment group versus 14.4% (21/146) in the control group (relative risk 0.37, 95% CI 0.170.80; p=0.008) Moreover, the odds of contrast-induced acute kidney injury decreased by 9% for