Imaging in Acute Kidney Injury, how not to harm patients

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Imaging in Acute Kidney Injury, how not to harm patients

  1. 1. Imaging in acute kidney injury: how to kill as few patients as possible Imaging in acute kidney injury: Joel Topf, M.D., JACN Just another clinical neprhologist Detroit, Michigan, USA St John Hospital and Medical Center http://www.PBfluids.com
  2. 2. Dopamine ANZICS Clinical Trials Group. Lancet 2000;356:2139-47 Fenoldopam Tumlin et al. Am J Kidney Dis (2005) vol. 46 (1) pp. 26-34 Anaritide Allgren et al. N Engl J Med (1997) vol. 336 (12) pp. 828-34 High dose furosemide Cantarovich et al. Am J Kidney Dis (2004) vol. 44 (3) pp. 402-9 High intensity dialysis VA/NIH Acute Renal Failure Trial Network et al. N Engl J Med (2008) vol. 359 7-20
  3. 3. Patients with primary diagnosis of AKI have higher mortality when they are: admitted on week-ends admitted to smaller hospitals James et al. Weekend Hospital Admission, Acute Kidney Injury, and Mortality. Journal of the American Society of Nephrology (2010) vol. 21 (5) pp. 845-851
  4. 4. We just don’t know what that “good care” looks like Despite the lack of evidence based success, good care makes a difference
  5. 5. • With out evidence we are left to wander with only our clinical sense to guide us – Avoid hypotension – Maintain urine flow – Avoid renal toxins – Maintain electrolyte balance – Maintain fluid balance
  6. 6. • Relate this to imaging – Avoid contrast induced renal toxicity – Avoid nephrogenic systemic fibrosis • With out evidence we are left to wander with only our clinical sense to guide us – Avoid hypotension – Maintain urine flow – Avoid renal toxins – Maintain electrolyte balance – Maintain fluid balance
  7. 7. Contrast
  8. 8. Hydration 0.9 normal saline +/- Isotonic bicarbonate Minimize contrast exposure Low or isosmolar contrast +/- N-Acetylcysteine
  9. 9. • 2,308 patients randomized to 1,200 mg of N-acetylcysteine x 4 doses • No improvement in: – Contrast induced nephropathy – Change in Cr – Need for dialysis – 30 day mortality or CV mortality • Sub group analysis looking at: – Age – Creatinine – Diabetes – Gender
  10. 10. Hydration 0.9 normal saline +/- Isotonic bicarbonate Minimize contrast exposure Low or isosmolar contrast +/- N-Acetylcysteine Techniques of particular interest to patients with acute kidney injury Dialysis Hemofiltration
  11. 11. Hemodialysis following contrast • Moon et al first demonstrated the ability to remove contrast in patients with pre-ESRD CKD by dialysis • A 6 hour hemodialysis session was able to remove 77% of the contrast load Moon et al. Nephron (1995) vol. 70 (4) pp. 430-7
  12. 12. Cr (mg/dL) Diabetes Contrast volume (mL) 4.5 DM 470 3.5 DM 980 3.2 177 4.1 377 2.4 259 5.7 313 7.5 97 6.1 DM 176 3.7 DM 227 4.5 377 3.0 476 5.7 DM 264 5.8 237 4.6 38% 340
  13. 13. First randomized controlled trial • N=30 • Cr 2.4 ±0.16 • DM 43% • 3 hours of HD started 63±6 min after contrast • Iopental, a low osmolar, non-ionic contrast • CIN defined as an increase of creatinine of 0.5 mg/dL at 48 hours Lehnert T, Et al Nephro Dial Transplant. 1998 13(2): 358-62.
  14. 14. Dialysis accelerated clearance dialysis • At 24 hours – Dialysis: 89% of contrast was gone – Control 83% of contrast was gone
  15. 15. But didn’t save the kidneys dialysis
  16. 16. Second RCT, 3 times the size • 113 patients • Cr 3.5 ± 1 (GFR 21 mL/min) • 33% diabetes • Hemodialysis started 120 minutes after contrast • 3 hours of HD Vogt et al. Am J Med (2001) vol. 111 (9) pp. 692-8
  17. 17. Solid line: dialysis Dotted line: control Contrast Dose (P=0.007) Control: 143 ±115 Hemodialysis: 210 ±143 Contrast Nephropathy (P=0.35) Control: 9 (16%) Hemodialysis 13 (24%) Hemodialysis (P=0.12) Control: 3 (5%) Hemodialysis 8 (15%)
  18. 18. Moon initiated dialysis 1.8 hours after exposure Lehnert initiated dialysis 1 hour after exposure Vogt initiated dialysis 2 hours after exposure Could earlier hemodialysis make a difference?
  19. 19. 7 patients with hemodialysis started 10 minutes prior to left heart cath 10 patients with IVF in the control group No need for further dialysis in either group No difference in the average serum Cr at 48 hours and 1 week Frank et al. Clin Nephrol (2003) vol. 60 (3) pp. 176-82
  20. 20. Largest dialysis trial • 424 patients • 3x the size of Vogt • Cr 1.3-3.5 • CIN defined as Cr rise of 0.5 at 48-72 hours • Three arms – Control 6.1% – Dialysis 15.9% – NAC 5.3% P=0.008 • Cr was not different at 30-60 days Reinecke H, Fobker M, Wellmann J, Et al. Clin Res Cardiol. 2007 Mar;96(3):130-9.
  21. 21. WHAT ABOUT THE WORST OF THE WORST? CKD stage 5 not on dialysis Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20
  22. 22. Lehnert Vogt • Cr > 3.5 • 90 patients randomized to dialysis or usual care – 4 hours, no UF – 81±32 min after contrast (45-180) • 24 hour CrCl on 4th day after contrast Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20 • No ITT analysis – 8 patient not analyzed – Insufficient f/u, NSAIDs, 2nd contrast exposure and NAC, off protocol
  23. 23. Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20 Cr and CrCl improved at 4 days
  24. 24. Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20 Cr is lower at day 4, peak and D/C
  25. 25. 1 14 0 5 2 18 Less temporary and permanent dialysis Less cases of severe CIN Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20
  26. 26. Dialysate Conventional Dialysis Diffusive Clearance
  27. 27. Ultrafilter 3+ liters/hour Replace all ultrafiltrate with sterile fluid at ideal plasma concentrations CVVH Convective clearance
  28. 28. What about hemofiltration • Marenzi et al. – Removal – Dilution • 114 patients (Cr = 3, 30% DM) randomized to – CVVH • Began 4-6 hours before contrast, continued for 24 hours – Hydration • CIN defined as an Cr increase >25 % from base-line • Emergency dialysis was protocolized: – oligouria for more than 48 hours despite use of more than 1 g of IV furosemide Marenzi et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med (2003) vol. 349 (14) pp. 1333-40
  29. 29. Contrast induced nephropathy (P=0.001) control: 28 (50%) hemofiltration: 3 (5%) Emergency HD control: 10 (18%) hemofiltration: 0 Hospital mortality (P=0.02) control: 8 (14%) hemodialysis: 1 (2%) 1 year mortality (P=0.01) control: 17 (30%) hemofiltration: 6 (10%)
  30. 30. • So the hemofiltration group differed from the control group by receiving: – More IVF – Removal of contrast – Anticoagulation – IV Alkali in the form of replacement fluid – ICU care
  31. 31. Follow up study • 92 patients • Three protocols – IVF 12 hours before and after contrast – CVVH for 18-24 hours after contrast – CVVH for 6 hours before and 18-24 after contrast • Designed to isolate contrast removal from fluid administration Marenzi G, Lauri G, Campodonico J, et al. Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients. Am J Med 2006;119:155–162.
  32. 32. Contrast nephropathy Emergent dialysis Hospital mortality IVF alone 12/30 (40%) 9/30 (30%) 6/30 (20%) CVVH after 8/31 (26%) 3/31 (10%) 3/31 (10%) CVVH before and after 1/31 (3%) 0/31 (0%) 0/31 (0%) Between group analysis P=0.0013 P=0.002 P=0.03
  33. 33. Before and after IVF
  34. 34. Pre/Post hemofiltration was 95% protective for contrast nephropathy compared to saline Pre/Post hemofiltration was 90% protective for contrast nephropathy compared to post hemofiltration
  35. 35. • So the pre/post hemofiltration group received – More IVF – Removal of contrast – Anticoagulation – Alkali exposure – ICU care
  36. 36. summary
  37. 37. • Hemodialysis is generally considered ineffective at protecting the kidneys from CIN Cruz et al. Am J Kidney Dis (2006) vol. 48 (3) pp. 361-71
  38. 38. However… • Data on the weakest kidneys was positive • Hemofiltration has been effective in two RCTs
  39. 39. • Swollen and thickened skin • Wood-like texture • Decreased range of motion • Presenting over days to weeks Nephrogenic systemic fibrosis Broome et al. AJR Am J Roentgenol (2007) vol. 188 (2) pp. 586-92
  40. 40. Twenty-four– month mortality was 48% and 20% in patients with and those without cutaneous changes of NSF, respectively Todd et al. Arthritis Rheum (2007) vol. 56 (10) pp. 3433-41
  41. 41. Novel Disease First patients with dermal features suggestive of scleromyxedema were identified in 1997 (published in 2000) – Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. The Lancet 2000; 356(9234):1000-1 19972001 A follow-up article on the same patient series. Characterized the histology and identified it as a novel disease they named Nephrogenic Fibrosing Dermopathy – Cowper SE, Su L, Robin H, Bhawan J, LeBoit PE. Amer J Dermatopathol 2001; 23(5): 383-393
  42. 42. 2000-2006 No idea of what triggered NSF • ACEi • Sevelamer • Epoetin • Ischemia • Clotting abnormalities –Anti-phospholipid antibodies • Abnormal Ca- Phos metabolism • Trauma • Acidosis
  43. 43. 5Five patients who received gadodiamide and developed NSF 4Four patients who also received gadodiamide but did not develop NSF
  44. 44. 10 months later
  45. 45. …we have not observed a single case of NSF among patients who were not exposed to gadodiamide…
  46. 46. Boyd et al. Gadolinium deposition in nephrogenic fibrosing dermopathy. Journal of the American Academy of Dermatology (2007) vol. 56 (1) pp. 27-30
  47. 47. Gadopentetate (magnevest) introduced 1988 Gadodiamide (Omniscan) approved 1993 1997 First case of NSF 1997 Galan A, Cowper SE, Bucala R: Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol 18: 614–617, 2006 Examined two tissue repositories to find unrecognized cases prior to 1997.
  48. 48. Co-factor to trigger NSF? • ACEi • Sevelamer • Epoetin • Ischemia • Clotting abnormalities –Anti-phospholipid antibodies • Abnormal Ca- Phos metabolism • Trauma • Acidosis
  49. 49. RISK OF NSF FOLLOWING GADOLINIUM
  50. 50. Not all gadolinium are equal • Gadolinium is insoluble in water and highly toxic • For human use gadolinium needs to be chelated • All the brands of gadolinium differ in the nature of the chelation molecule
  51. 51. Brand name generic Class of chelation agent K (log dissociation constant) Optimark Gadoversetamide Linear, non-ionic 16.8 Omniscan Gadodiamide 16.9 Vasovist Gadofosveset Linear, ionic 22.1 Magnesvist Gadopentetate 22.5 Multihance Gadobenate 22.6 Eovist Gadoxetate 23.5 Gadovist Gadobutrol 21.8 Prohance Gadoteridol Cyclic, ionic 23.8
  52. 52. Gadodiamide K=16.9 Gadoteridol K=23.8 1,000,000x more free, toxic Gd
  53. 53. Gadodiamide Gadoteridol 1,000,000x as tall Mount Elbert 14,440 feet Thickness of an iPod, 0.26 inches
  54. 54. 13 23 4.7 2.6 2.2Omniscan Magnevist Optimark Multihance Prohance Adapted from data presented at Joint Meeting of the Cardiovascular and Renal Drugs and Drug Safety and Risk Management Advisory Committees Estimated doses (millions)* The gadolinium matters *2005-2008 IMS National Sales Perspectives™, Year 2005- 2009 ** post marketing adverse events. FDA Office of Surveillance and Epidemiology
  55. 55. • 2.4% risk – 3 patients of 87 who received 123 exposures – Deo A, Fogel M, Cowper SE. Clin J Am Soc Nephrol 2007;2:264–7. • 18% risk – 18/102 patients exposures to gadodiamide exposure – Rydahl C, Thomsen HS, Marckmann P. Invest Radiol 2008;43:141– 4. • 0% risk – 0 of 141 exposures to gadoteridol (ProHance) – Reilly RF. Clin J AmSoc Nephrol 2008;3:747–51. • 30% risk – 16/54. Prospectively examined patients for dermatologic signs of NSF after exposure to gadopentetate – Todd DJ, Kagan A, Chibnik LB, et al. Arthritis Rheum 2007;56:3433–41. • 8.4% risk – Patients with a GFR <15 mL/min (not on dialysis) receiving gadolinium developed NSF – Prince MR, Zhang H, Morris M, et al. Radiology 2008;248:807–16. • 0.05% risk with gadodiamide • 0.002% risk with gadopentetate – Used all MRI scans as the denominator – Wertman R, Altun E, Martin DR, et al. Radiology 2008;248:799 – 806
  56. 56. NSF in acute renal failure • The condition occurs in acute renal failure but much of the focus has been on chronic dialysis patients Todd DJ, Kagan A, Chibnik LB, et al. Arthritis Rheum 2007;56:3433–41.
  57. 57. • Perez-Rodriguez looked at 33 cases of biopsy proven NSF from a single center – 7 were AKI (21%) – 5 subsequently recovered renal function, – That did not lead to improved symptoms Perez-Rodriguez J, Lai S, Ehst BD, Fine DM, Bluemke DA 2009 Radiology, 250, 371-377
  58. 58. Prince et al. Radiology (2008) vol. 248 (3) pp. 807-16 11 of 15 (73%)patients were in acute kidney injury
  59. 59. • 4 of 12 cases (33%) from a single institution were in acute renal failure • 3 of the 4 were due to hepatorenal syndrome Broome et al. AJR Am J Roentgenol (2007) vol. 188 (2) pp. 586-92
  60. 60. Avoiding NSF • Because there is no effective therapy for NSF, avoidance of exposure is the best option • View the unenhanced images to verify the need for gadolinium enhancement • Minimize dose – avoid MR angiogram • Low risk gadolinium- containing contrast agent
  61. 61. Brand name generic Class of chelation agent K (log dissociation constant) Optimark Gadoversetamide Linear, non-ionic 16.8 Omniscan Gadodiamide 16.9 Vasovist Gadofosveset Linear, ionic 22.1 Magnesvist Gadopentetate 22.5 Multihance Gadobenate 22.6 Eovist Gadoxetate 23.5 Gadovist Gadobutrol 21.8 Prohance Gadoteridol Cyclic, ionic 23.8
  62. 62. • Gadolinium contrast agents are rapidly cleared – half life of 1.3 hours in healthy volunteers. – In CKD the half-life can be extended from 30 to 120 hours. • 70 dialysis patients, 4 hours hemodialysis session Okada S, Katagiri K, Et al. Acta Radiol 2001; 42: 339-341.
  63. 63. Prince et al. Radiology (2008) vol. 248 (3) pp. 807-16 14 of 15 patients had either no dialysis or delayed dialysis
  64. 64. • 33 cases of NSF – 8 not on dialysis – 5 on peritoneal dialysis – 20 on hemodialysis • 7 received HD on the day of exposure • 13 unable to determine the timing of dialysis in regards to gadolinium exposure Perez-Rodriguez et al. Radiology (2009) vol. 250 (2) pp. 371-7
  65. 65. • 3 of 12 cases (33%) received dialysis on the day of exposure and then daily for three days • And they developed NSF Broome et al. AJR Am J Roentgenol (2007) vol. 188 (2) pp. 586-92
  66. 66. Recovery of renal function • Some authors report improvement in symptoms with improvement in renal function – Cowper. Am J Kidney Dis (2005) vol. 46 (4) pp. 763-5 • Perez-Rodriguez reported on 5 cases of NSF in association with renal failure with a liver transplant. – Every patient recovered renal function within 6 weeks, none had improvement in NSF – One patient’s kidney function recovered days prior to developing skin changes Perez-Rodriguez et al. Radiology (2009) vol. 250 (2) pp. 371-7
  67. 67. Summary • Nephrogenic Systemic Fibrosis is a devastating complication • The risk, in patients with decreased renal function and inflammatory insults, likely runs from 5 to 30% following a single Gd exposure • Though dialysis if suggested as a way to reduce harm, there are case reports of patients who have developed NSF despite this
  68. 68. Summary • Avoid gadolinium • Use safer formulations of gadolinium, Gadovist, ProHance if necessary
  69. 69. DOES ANYBODY HAVE ANY QUESTIONS? The big finish

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