Update in Contrast Induced Nephropathy

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1 Update in Contrast Induced Nephropathy Yves Pirson Service de Néphrologie, Clin. Univ. St-Luc - UCL

2 A 76-year-old man with - type 2 diabetes - CKD (ser. creat.: 1.8 mg/dl; GFR: 32) presents with angina pectoris indication for elective coronarography

3 Course of kidney function Ser. Créat.: (mg/dl) Coro Definition of CIN : - either in ser. creat. > 0.5 mg/dl - or > 25% increase in ser. creat Day

4 Risk score for prediction of CIN after percutaneous coronary intervention Risk factor Score Age > 75 4 Diabetes 3 Systolic BP < 80 mmhg durant > 1h 5 GFR Contrast volume 1/100 ml Risk score Risk of CIN (%) Risk of dialysis (%) > (Mehran R et al., J Am Coll Cardiol 2004; 44: 1393)

5 Prevalence of CKD in the US (Andersen PE, World J Radiol 2012; 4: 253)

6 Is it important to avoid CIN? Pathophysiology of CIN Risk factors for developing CIN How to prevent CIN?

7

8 (Maioli M, Circulation 2012; 125: 3099)

9 (Maioli M, Circulation 2012;125:3099)

10 12% 2% (Maioli M, Circulation 2012; 125: 3099)

11 Effect of acute kidney injury frequency on survival to stage 4 CKD (Chawla LS, Kidney Int 2012; 82: 516)

12 (Chawla LS, Kidney Int 2012; 82: 516)

13 Is it important to avoid CIN? Pathophysiology of CIN Risk factors for developing CIN How to prevent CIN?

14 (Calvin AD, Nat Rev Nephrol 2010; 6: 679)

15 (Calvin AD, Nat Rev Nephrol 2010; 6: 679)

16 Is it important to avoid CIN? Pathophysiology of CIN Risk factors for developing CIN How to prevent CIN?

17 Patient-related risk factors for CIN Classical Age > 70 CKD Diabetes mellitus Congestive heart failure Dehydration (! diuretics) Use of nephrotoxic drugs (NSAID, anticalcineurins, some antivirals) Recently recognized risk factors for AKI in general Obesity (Soto GJ, Crit Care Med 2012; 40: 260) Albuminuria with preserved egfr

18 Adjusted hazard ratio for acute kidney injury according to egfr and albuminuria Albumin-to-creatinine ratio > 300 mg/g mg/g < 30 mg/g (Gansevoort R, Kidney Int 2011; 80:93)

19 Is it important to avoid CIN? Pathophysiology of CIN Risk factors for developing CIN How to prevent CIN?

20 How to prevent CIN? Assessment of the individual risk for CIN Minimisation of this risk Volume expansion Pharmacological prevention? Non-pharmacological preconditioning? Clinical practice

21 Screening of the population at risk for CIN Ser. creat. in all patients at risk : egfr < 45 Simple risk-factor questionnaire : - known CKD? - diabetes? - c-v disease? - list of current medications - contrast media within the last 3 days? Urinary-protein screening advisable

22 In patients with increased risk : is contrast injection absolutely needed?

23 How to prevent CIN? Assessment of the individual risk for CIN Minimisation of this risk Volume expansion Pharmacological prevention? Non-pharmacological preconditioning? Clinical practice

24 Minimisation of the risk Discontinue concurrent nephrotoxic medications (NSAID, diuretics) whenever possible for > 3 days No compelling reason to discontinue ACE-I/ARB Avoid repeat contrast injection within 72 hours Use the lowest volume of contrast Apply a prevention protocol

25 Which prevention strategy?

26 How to prevent CIN? Assessment of the individual risk for CIN Minimisation of this risk Volume expansion Pharmacological prevention? Non-pharmacological preconditioning? Clinical practice

27 «Despite the recognition of volume depletion as an important risk factor for AKI, there are no RCT that have directly evaluated the role of fluids vs placebo in the prevention of AKI» (KDIGO) There is however a large consensus as to recommend volume expansion in at-risk patients But : Oral or i-v? Na chloride or bicarbonate?

28 (n = 79) NaCl 1g/10kg/d per os for 2 days (n = 77) 0.9% NaCl i.v. 15 ml/kg for 6 h before (n = 80) idem arm B + theophylline 5mg/kg 1 h before (n = 79) idem arm B + furosemide 3mg/kg i.v. after

29 Arm A (n = 27) NaCl i.v. 1 h before 6 h after Arm B (n = 21) Bicar i.v. 1 h before 6 h after Arm C (n = 22) Oral H 2 O 500 ml before 600 ml after Arm D (n = 21) Idem C + oral bicar 4g before and 2g after

30 Oral route vs i-v route «We recommend not using oral fluids alone in patients at increased risk of CIN» KDIGO. Kidney Int 2012; Suppl 2: 69 «We suggest using the oral route for hydratation, on the premise that adequate intake of fluid and salt are assured (2C). We suggest that, when oral intake of fluid and salt is deemed cumbersome in patients at increased risk of CIN, hydration should be performed by intravenous route (2C)» ERBP. Nephrol Dial Transplant 2012; 27: 4263

31 Clinical trials comparing i-v bicarbonate with i-v saline for CIN (Weisbord SD, Clin J Am Soc Nephrol 2013;8: 1618)

32 Meta-analyses of bicarbonate vs saline for CIN prevention (Weisbord SD, Clin J Am Soc Nephrol 2013;8: 1618)

33 «We recommend volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no volume expansion, in patients at increased risk for CIN (1A)» KDIGO and ERBP 2012

34 How to prevent CIN? Assessment of the individual risk for CIN Minimisation of this risk Volume expansion Pharmacological prevention? Non-pharmacological preconditioning? Clinical practice

35 83 patients ser.creat ~ 2,4 mg/dl enhanced CT NaCl 0.45 % i-v 12h before 12h after + NAC 600 mg 2x/j J-1 and J0 (Tepel M et al. N Engl J Med 2000; 343: 180-4)

36 Clinical trials comparing NAC with placebo for CIN prevention 15 positive vs 21 negative studies 17 meta-analyses with conflicting conclusions! «We suggest using oral NAC, together with i.v. isotonic cristalloids, in patients at increased risk of CIN (2D)» KDIGO «We suggest using oral N-acetyl-cysteine (NAC) only in patients who receive appropriate fluid and salt loading (2D). We recommend not using oral NAC as the only method for prevention of CIN (1D)» ERBP

37 2 x 2 factorial design - bicarbonate vs saline - NAC vs placebo 90-day composite end-point (death or dialysis or persistant decline in kidney function) > participants, USA and Australia (Weisbord SD, Clin J Am Soc Nephrol 2013;8: 1618)

38 Atorvastatin 80 mg within 24 h before contrast vs placebo + Bicarbonate and NAC in all patients (Quintavalle C, Circulation 2012; 126: 3008)

39 9 RCTs, 1536 patients 33% less risk of CIN among patients receiving ascorbic acid

40 How to prevent CIN? Assessment of the individual risk for CIN Minimisation of this risk Volume expansion Pharmacological prevention? Non-pharmacological preconditioning? Clinical practice

41 Preconditioning : 4 cycles of alternating 5 inflation and 5 deflation of a standard BP cuff to the individual SBP + 50 mmhg, within 1 before coronarography 50 pts vs 50 controls S creat > 1.4 mg/dl or egfr < 60 (Er F, Circulation 2012; 126: 296)

42 Regional Ischemic Preconditioning Protects Remote Virgin Myocardium From Subsequent Sustained Coronary Occlusion Przyklenk K, Circulation 1993; 87: 893

43 Effect of IPC on serum creatinine (Wever KE, PlosOne 2012;7: e32296)

44 What is the molecular mechanism(s) behind ischemic preconditioning? inducible NO (Park KM, 2003)? adenosine (Wever KE, 2011)? hypoxia inducible factor 1 α (Malfoud, 2012)?.

45

46 How to prevent CIN? Assessment of the individual risk for CIN Minimisation of this risk Volume expansion Pharmacological prevention? Non-pharmacological preconditioning? Clinical practice

47 Conclusions 1. Among at-risk patients (age >75; suspicion of CKD; diabetes, congestive heart failure etc ) check egfr 2. If egfr < 40 : - discontinuation diuretics, NSAID - i-v saline 1 ml/kg/h for 24 h - use the lowest dose of contrast

48

49 (Bolognese L, Am J Cardiol 2012; 190:67)

50 (Gurm H, J Am Coll Cardiol 2011; 58:907)

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