IV contrast and Contrast-Induced Acute Kidney Injury. Dr Sarah Constantine FRANZCR The Queen Elizabeth Hospital University of Adelaide, SA.

Contrast-induced acute kidney injury. CI-AKI is defined as an acute decrease in renal function, occurring within 3 days of administration of iodinated contrast, (in the absence of an alternative aetiology).1 transient event serum creatinine peaks at approx. 72 hours slowly returns to normal over 2 weeks small number will progress to established renal failure 1. RANZCR Guidelines 2009

Contrast-induced acute kidney injury. 15% of ICU patients2, 1.5% of unselected patients3 a deterioration in serum markers of renal function after administration of iodinated contrast is very common almost always an “alternative aetiology” - or compounding factors How do we know the decline in renal function is due to iodinated contrast? 2. Hoste et al 2011 Intensive Care Med 3. Laskey et al 2007 J Am Coll Cardiol

Contrast-induced acute kidney injury. it doesn’t matter!! the end result is the same regardless of the cause

Other Risks of Poor Renal Function reduced success of procedures increased bleeding increased MI increased number of deaths 3. Laskey et al 2007 J Am Coll Cardiol

Risk Factors for CI-AKI. advanced age (over 75 years) pre-existing renal disease prolonged hypotension (systolic BP less than 80mmHg for 1 hour or more within 48 hours of contrast administration) congestive cardiac failure diabetes mellitus cirrhosis multiple myeloma

Risk Factors for CI-AKI. dehydration anaemia low serum albumin (< 35 g/L) medications – ACE inhibitors, angiotensin II blockers, NSAIDs, diuretics, nephrotoxic antibiotics eg gentamicin

Reducing the risk of CI-AKI. identify and modify risk factors (where possible) defer scan alternative imaging technique involve renal physicians monitor renal function

SA Renal Network

Outpatient Risk Assessment ask about risk factors recent serum creatinine/eGFR (within 3 months) oral hydration if necessary rebook with more aggressive prevention if necessary

Inpatient Risk Assessment check renal function and risk factors at time of scan request organise hydration, NAC, cease medication etc ensure renal function is rechecked within 72 hours post scan

4. SA Renal Network 2010

Proven methods of reducing the risk of CI-AKI. adequate hydration5 – easy, cheap, quick, safe, take care in CCF volume of contrast6 – use the minimum necessary to obtain a diagnostic scan 5. Balemans et al 2012 Radiology 6. Gurm et al 2011 Am J Coll Cardiol

Hydration 747 patients receiving IV contrast high risk patients hydrated, low risk patients not hydrated serum creatinine rechecked 3 – 5 days later incidence of CI-AKI was 2.5% 5. Balemans et al 2012 Radiology

Hydration 5. Balemans et al 2012 Radiology

Methods of possibly reducing the risk of CI-AKI. N-acetylcysteine7 – conflicting evidence as to its success, does no harm, expensive sodium bicarbonate8 – thought to be effective by some authors 7. Sergie 2012 Catheter Cardiovasc Interv 8. Hiremath 2010 Nephrol Dial Transplant

Experimental/non-proven methods statins ascorbic acid (vitamin C) β1 blockers loop diuretics theophylline 5HT receptor blockers systemic hypothermia

Special Situations: Code Stroke, STEMI time is critical in this patient group life potentially at risk assess risk factors AFTER scan, modify where possible no significant decreases in renal function in our experience

Special Situations: CRF patients unique group with severe, chronic renal impairment liase with renal physicians background renal function may be important in this group transplant patients

Estimating Renal Function serum creatinine measures the effect of both production (from muscle) and excretion (by the kidneys) creatinine clearance provides a good estimate of GFR calculated via the Cockcroft – Gault equation accuracy has been verified9 not reliable in extremes of body size, rapidly changing renal function eg ARF 9. Faull Aust Presc 2007

Calculated GFR and CrCL Cockcroft-Gault Equation*: Age = years Weight = kg Creatinine = μmol/L Creatinine clearance = (mL/min) (140 – age) x weight serum creatinine x 0.815 * multiply by 0.85 for females overestimates GFR in severely impaired renal function (< 20mL/min), unreliable in morbid obesity or severe malnutrition1 9. Faull Aust Presc 2007

Estimated Glomerular Filtration Rate assumes patient is average body size (what is average??) surface area of 1.73m2, hence the units mL/min/1.73m2 screening tool overdose small patients, underdose large patients

Contrast Dose to Cr Ratio Cigarroa formula: 5ml per kg divided by serum creatinine (mg/dL)3 in patients with normal renal function, a ratio of 1:1 is considered safe, higher ratios are associated with a higher risk increasing evidence that this is effective ratio in Australia - 88.4 : 1 (μmol/L)

Why not just use serum creatinine? creatinine rise from 60 to 120 is still in the normal range, although GFR has halved as renal function declines with age, an 80 year old with the same creatinine as a 20 year old will have about half the renal function

GFR or CrCL? not the same entity CrCL is an indirect measure of renal function, the rate at which creatinine is removed from the body CrCL requires blood sample + 24 hour urine collection GFR is a direct measure of renal function, the rate at which ultrafiltrate is formed by the glomerulus. GFR requires injection of radioisotope, then 2 blood samples to measure plasma clearance calculated methods less accurate but more practical 9. Faull Aust Presc 2007

Contrast Dose to CrCL Ratio several studies now published iodinated contrast has linear pharmacokinetics: systemic clearance of contrast equals glomerular filtration rate plot serum contrast concentration vs time area under the curve (AUC) represents systemic exposure (and therefore toxicity) ratio of contrast dose to eGFR or CrCL approximates AUC10 10. Sherwin et al 2005 Invest Radiol

Blood Concentration vs Time11 contrast dose CrCL AUC ≈

Contrast Dose to CrCL Ratio several studies now published iodinated contrast has linear pharmacokinetics: systemic clearance of contrast equals glomerular filtration rate plot serum contrast concentration vs time area under the curve (AUC) represents systemic exposure (and therefore toxicity) ratio of contrast dose to eGFR or CrCL approximates AUC10 10. Sherwin et al 2005 Invest Radiol

Contrast Volume to Cr CL Ratio. Gurm et al 2011 Am J Coll Cardiol

Contrast Dose to GFR Ratio. Nyman et al 2005 Acta Radiol

Contrast Dose to Cr CL Ratio Author Ratio Low Risk High Risk Laskey et al3 volume CrCL Not stated ≥ 3.7 Gurm et al6 < 2 > 3 Altmann et al13 ≤ 6 (4%) > 6 (14%) Nyman et al12 gm-Iodine eGFR < 1 (2%) > 1 (25%) Nyman et al14 < 1 (3%) ≥1 (25%)

Summary screen patients for CI-AKI risk – history, blood results consider non-contrast scan, other tests minimise risk with prevention protocol HYDRATION is important role for contrast to renal function ratios?

References RANZCR Guidelines for Iodinated Contrast Administration. March 2009, RANZCR Website. Hoste EA et al. Epidemiology of contrast-associated acute kidney injury in ICU patients: a retrospective cohort analysis. Intensive Care Med 2011; 37: 1921 – 31. Laskey WK et al. Volume-to-Creatinine Clearance Ratio. J Am Coll Cardiol 2007; 50: 584 – 90. SA Renal Network. Protocol For Prevention Of Contrast-induced Acute Kidney Injury, 2010. Balemans CE et al. Epidemiology of contrast material-induced nephropathy in the era of hydration. Radiology 2012; 263: 706 - 13. Gurm HS et al. Renal Function-Based Contrast Dosing to Define Safe Limits of Radiographic Contrast Media in Patients Undergoing Percutaneous Coronary Interventions. J Am Coll Cardiol 2011; 58: 907 – 14. Sergie Z, Mehran R. NAC and CIN Prevention: Mounting Evidence of Inefficacy. Catheter Cardiovasc Interv 2012; 79: 927 – 8. Hiremath S, Brar SS. The evidence for sodium bicarbonate therapy for contrast-associated acute kidney injury: far from settled science. Nephrol Dial Transplant 2010; 25: 2802 – 4. Faull R, Lee L. Prescribing in renal disease. Aust Prescr 2007; 30: 17 – 20. Sherwin PF et al. Contrast Dose–to–Creatinine Clearance Ratio as a Potential Indicator of Risk for Radiocontrast-Induced Nephropathy. Invest Radiol 2005; 40: 598 – 603. DiPiro JT et al. Pharmacotherapy: A pathophysiologic Approach. 7th Edn. Nyman U et al. Contrast-Medium-Induced Nephropathy Correlated to the Ratio Between Dose in Gram Iodine and Estimated GFR in ml/min. Acta Radiol 2005; 46: 830 – 42. Altmann DB et al. Use of the Contrast Volume to Estimated Creatinine Clearance Ratio to Predict Renal Failure After Angiography. J Interven Cardiol 1997; 10: 113 – 9. Nyman U et al. Contrast Medium Dose-to-GFR Ratio: A Measure of Systemic Exposure to Predict Contrast-Induced Nephropathy after Percutaneous Coronary Intervention. Acta Radiol 2008; 49: 658 – 67.