Optimal Use of Iodinated Contrast Media In Oncology Patients. Focus on CI-AKI & cancer patient management

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1 Optimal Use of Iodinated Contrast Media In Oncology Patients Focus on CI-AKI & cancer patient management Dr. Saritha Nair Manager-Medical Affairs-India & South Asia GE Healthcare

2 Context Cancer patients are vulnerable to kidney damage1,2 Potentially restricting effective therapy2 Imaging plays a pivotal role at many stages of cancer management, but may add to the AKI risk2,3 CT CT CT CT Diagnosis Staging Response assessment Follow-up 1. Salahudeen AK et al. Clin J Am Soc Nephrol 2013; 8: Cicin I et al. Eur Radiol 2014; 24:

3 AKI in cancer patients AKI: acute kidney injury

4 MD Anderson Cancer Center: cross-sectional analysis Objective To determine incidence, clinical correlates and outcomes of AKI in cancer patients Design Cross-sectional analysis of prospectively collected data on 3,558 patients admitted to medical, surgical or radiological service over 3 months in 2006 Eligibility Any patient admitted with SCr measurements at admission and at least once during hospital stay AKI definition 50% increase in SCr (modified RIFLE) AKI: acute kidney injury Salahudeen AK et al. Clin J Am

5 RIFLE: Risk, Injury, Failure, Loss, ESRD CR/ GFR criteria UO criteria Cr increased 1.5 or GFR decreased >25% UO <0.5 ml/kg/hour for 6 hours Cr increased 2 or GFR decreased >50% UO <0.5 ml/kg/hour for 12 hours Cr increased 3 or GFR decreased >75% or Cr 4 mg/dl (with acute rise of 0.5 mg/dl) UO <0.3 ml/kg/hour for 24 hours or Anuria for 12 hours Risk Injury Failure Loss Persistent ARF: complete loss of renal function for >4 weeks ESRD End-stage renal disease ARF: acute renal failure Figure adapted from Bellomo R et al.

6 Acute Kidney Injury Network (AKIN) Diagnostic criteria An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in SCr of more than or equal to 0.3 mg/dl ( 26.4 μmol/l), a percentage increase in SCr of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg/hour for more than 6 hours). Classification/ staging for AKI Stage Serum creatinine criteria Urine output criteria 1 Increase in SCr of more than or equal to 0.3 mg/dl Less than 0.5 ml/kg/hour for more ( 26.4 μmol/l) or increase to more than or equal to than 6 hours 150% to 200% (1.5- to 2-fold) from baseline 2 Increase in SCr to more than 200% to 300% (>2- to 3-fold) from baseline 3 Increase in SCr to more than 300% (>3-fold) from baseline (or SCr of more than or equal to 4.0 mg/dl Less than 0.3 ml/kg/hour for 24 [ 354 μmol/l] with an acute increase of at least hours or anuria for 12 hours 0.5 mg/dl [44 μmol/l]) AKI: acute kidney injury Less than 0.5 ml/kg/hour for more than 12 hours Mehta R et al. Crit Care

7 Timing of AKI in cancer patients: MD Anderson analysis More than half of the AKI cases occurred >2 days after admission AKI: acute kidney injury ( 50% Figure adapted from Salahudeen AK et al.

8 Mortality in cancer patients with AKI: MD Anderson analysis In-hospital mortality: 4.6% overall p<0.001 AKI: acute kidney injury ( 50% Odds ratio with AKI vs no AKI: 7.41 (95% CI ), univariate analysis 4.47 (95% CI ), multivariate analysis Salahudeen AK et al. Clin J Am Soc

9 Healthcare use in cancer patients with AKI: MD Anderson analysis Length of hospital stay p<0.001 Total hospital costs p<0.001 Median length of stay increased 100% and median hospital costs increased 106% in patients with AKI vs those without AKI Salahudeen AK et al. Clin J Am Soc AKI: acute kidney injury ( 50% Nephrol 2013; 8:

10 AKI risk factors in cancer patients and the role of CM AKI: acute kidney injury CM: contrast medium

11 Multiple risk factors for AKI Pre-existing kidney dysfunction Use of contrast media Age >65 years Nephrotoxic drugs Diabetes mellitus Severe dehydration Advanced CHF AKI Prolonged hypotension Reduced LVEF Reduced effective intravascular volume Renal transplantation Anaemia Multiple myeloma Sepsis Andreucci M et al. Biomed Res Int AKI: acute kidney injury 2014; 2014:

12 Multiple risk factors for AKI Pre-existing kidney dysfunction Use of contrast media Age >65 years Nephrotoxic drugs Diabetes mellitus Chemotherapy (e.g. cisplatin) Loop diuretics Severe dehydration NSAIDs Advanced CHF AKI (e.g. aminoglycosides, Antimicrobials amphotericin B) Reduced LVEF Prolonged hypotension Immunomodulators (e.g. ciclosporin, tacrolimus) Reduced effective intravascular volume Renal transplantation Anaemia ACE: angiotensinconverting enzyme Multiple myeloma Sepsis Andreucci M et al. Biomed Res Int

13 What factors increase the risk of AKI in cancer patients?

14 Risk of AKI in cancer patients: MD Anderson analysis Multivariate analyses for factors associated with AKI in 3,558 patients admitted to MD Anderson cancer center Antibiotics 1.52 ( ), p=0.004 Chemotherapy 1.61 ( ), p<0.001 Diabetes 1.89 ( ), p<0.001 Hyponatraemia 1.97 ( ), p<0.001 Transfer to ICU 2.34 ( ), p<0.001 IV CM 4.55 ( ), p< Odds ratio (95% confidence interval) AKI: acute kidney injury ( 50% increase in serum creatinine) Salahudeen AK et al. Clin J Am

15 Risk factors for AKI in cancer patients in an emergency setting Overall AKI incidence: 8.0% (66/820 patients) Peritoneal seeding 1.75 ( ) BUN/Cr > ( ) Liver cirrhosis 2.82 ( ) Hypotension before CT 3.95 ( ) Consecutive CECT* 4.09 ( ) Odds ratio (95% confidence interval) *Non-simultaneous CECT performed 24 Figure adapted from Hong SI et al. 72 hours after first scan

16 Risk factors for AKI in cancer patients in an emergency setting Overall AKI incidence: 8.0% (66/820 patients) Peritoneal seeding 1.75 ( ) BUN/Cr > ( ) Liver cirrhosis 2.82 ( ) Hypotension before CT 3.95 ( ) Consecutive CECT* 4.09 ( ) Odds ratio (95% confidence interval) *Non-simultaneous CECT performed 24 Figure adapted from Hong SI et al. 72 hours after first scan

17 Cumulative effect of chemotherapy and CM on AKI Chemotherapy before CECT (Cicin et al)1 p=0.005 AKI: acute kidney injury (Cicin et al: 25% or 0.5 mg/dl increase in serum creatinine CECT before chemotherapy (Sendur et al)2 p= Cicin I et al. Eur Radiol 2014; 24:

18 Overlapping mechanisms of chemotherapy- and CM-induced AKI1,2 Chemotherapy CM Changes in endothelin/ adenosine levels Vasoconstriction/reduced renal blood flow Tissue ischaemia Endothelial damage Inflammation/production of oxygen free radicals Direct cytotoxic effects 1. Cicin I et al. Eur Radiol 2014; 24:

19 Impact of CM osmolality on AKI risk AKI: acute kidney injury CM: contrast media

20 CM profiles Name Benzene rings Ionicity Iodine content, mg/ml Diatrizoate Monomer Ionic ,938 Iothalamate Monomer Ionic ,400 Ioxithalamate Monomer Ionic ,160 Dimer Ionic Iohexol Monomer Non-ionic Iopamidol Monomer Non-ionic Ioversol Monomer Non-ionic Iopromide Monomer Non-ionic Iobitridol Monomer Non-ionic Iomeprol Monomer Non-ionic Iodixanol Dimer Non-ionic Ioxaglate Viscosity at Osmolality 37 C, mosm/kg H2O mpa s Adapted from Davidson C et al. Am J Cardiol 2006; 98 (Suppl): 42K 58K.

21 Risk of AKI with IOCM vs LOCM: learning from intra-arterial use ( high-risk patients) AKI: acute kidney injury (serum creatinine increase 0.5 mg/dl); Figure adapted from

22 Risk of AKI with iodixanol vs iopromide in high-risk patients p=0.037 AKI: acute kidney injury p=0.012 Nguyen SA et al.

23 Subclinical AKI and cumulative effect of nephrotoxic factors in cancer AKI: acute kidney injury

24 GFR levels can be sustained by renal functional reserve, even during kidney injury With sufficient renal functional reserve, up to 50% of nephrons can be lost with no clinical impact on GFR or SCr levels Figure adapted from Sharma A et al. GFR: glomerularnephron filtration Clin Pract 2014; 127:

25 With repeated kidney injury, renal functional reserve is lost AKI: acute kidney injury; CKD: Figure adapted from Sharma A et al.

26 Several biomarkers have been identified that can indicate subclinical AKI Figure adapted from Nejat M et al. Kidney Int 2012; 81: AKI: acute kidney injury

27 Management of AKI in cancer patients AKI: acute kidney injury

28 International guidelines on AKI management in cancer patients1,2 GFR measurement hours after procedure AKI: acute kidney injury 1. Kellum JA et al. Kidney Int Suppl 2012; 2:

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