Jayant Bagai MD, FSCAI and Craig J. Beavers PharmD, FAHA, AACC, BCPS-AQ Cardiology, CACP 

As older patients with comorbidities such as diabetes and renal disease are increasingly treated in the cath lab, we encounter more patients at high risk for contrast-induced renal dysfunction. The term “contrast-induced nephropathy (CIN)” has traditionally been defined as an increase in serum creatinine (sCr) > 0.5 mg/dl or > 25% increase from baseline, within 72 hours of contrast administration. This definition has recently been replaced by “contrast-induced acute kidney injury (CI-AKI).” CI-AKI is now defined in the KDIGO guidelines (Kidney Disease—Improving Global Outcomes) as a rise in Cr > 0.3 mg/dl or > 50% from baseline.¹ In this Tip-of-the-Month, we will summarize quality measures to help the proceduralist and cath lab staff decrease the risk of CI-AKI using evidence-based risk stratification and prevention strategies.

Incidence, risk factors, and consequences of CI-AKI

CI-AKI is the third most common cause of hospital-acquired renal failure after decreased renal perfusion and medications. Coronary angiography (CA) and percutaneous coronary intervention (PCI) are more likely than other contrast studies to result in CI-AKI, probably due to the often-urgent nature of these procedures in high-risk patients.² The incidence of CI-AKI following CA and PCI varies from 2.8–13% in selected studies, depending on the risk factor profile of patients studied.^2,3 Several risk factors for CI-AKI have been identified. (Table 1) Of these, pre-existing chronic kidney disease (CKD) is a major risk factor. The presence of CKD more than doubles the risk of CI-AKI in diabetics, and in these patients CI-AKI strongly predicts one-year mortality (OR 2.75; p<0.01).⁴ Another major risk factor is anemia, with each 3% decline in hematocrit increasing the odds of CI-AKI by 11%.⁵ In-hospital mortality has been reported at 14–22% and is much higher in the 8–10% of patients who require in-hospital dialysis.^2,6 CI-AKI is associated with prolongation of hospital stay, myocardial infarction (MI), short- and long-term mortality, persistent renal impairment, and progression of CKD.⁷

Quality measures to decrease risk of CIN

1. Use risk calculators to predict risk of CI-AKI

• Mehran score (Figure 1)—Important modifiable factors based on this score are contrast volume and placement of an IABP.³

• SCAI PCI risk assessment tool calculates risk of in-hospital AKI and dialysis

2. Administer pre and post-procedural hydration

 • 1-1.5 ml/kg/hour NaCl x 3-12 hours pre-procedure, and 12-24 hours post procedure has been advocated in the 2011 ACC/AHA/SCAI PCI guidelines.⁸

• LVEDP-guided hydration: 3 ml/kg 0.9% NaCl x 1-hour pre-procedure, and 5 ml/kg/h (LVEDP < 13 mmHg), 3 ml/kg/h (LVEDP 13–18 mmHg) and 1.5 ml/kg/h (LVEDP > 18 mmHg) x 4 hours post-procedure. This protocol from the POSEIDON trial lowered CI-AKI by 60%.⁷ However, the trial had a relatively small number of patients (n=396) and excluded the following categories of patients: decompensated heart failure, emergency PCI such as for ST-elevation myocardial infarction (STEMI), dialysis and history of heart/kidney transplant, mechanical aortic valve. Its results have not been validated in larger and more inclusive populations.

3. Limit contrast volume
   The risk of CI-AKI increases by 12% for every 100 ml of contrast administered.⁶ The CV/CCC or contrast volume/calculated creatinine clearance ratio (using the Cockcroft-Gault equation) should be kept less than three and ideally less than two.⁹ The maximal acceptable contrast dose (MACD) equation, calculated as 5x body weight (kg)/ serum creatinine, was first developed 20 years ago. It has since been validated by more recent studies that have shown a progressive increase in the risk of CI-AKI when the so-called Contrast Ratio (contrast volume used during the procedure/MACD) exceeds one. The MACD or CV/CCC ratio should be stated during time-out and the operator notified by the staff when the ratio is exceeded.
   
   Practical methods of lowering contrast volume are: limiting number of injections, using co-axial engagement with adequate length catheters, using ECHO in lieu of left ventriculography, 5F catheters, bi-plane imaging, automated injection systems, contrast reduction systems, and intravascular ultrasound (IVUS).

4. Consider use of transradial access (TRA) compared to transfemoral access (TFA) in patients undergoing CA and PCI for acute coronary syndrome, especially in patients with Mehran score > 10, Killip class III/IV and eGFR < 60 ml/min/1.73 m². TRA lowered incidence of CI-AKI by 23% compared with TFA in the AKI-MATRIX trial.¹⁰ The risk of dialysis was lowered by 55% in the group that did not require access site crossover. The main benefit of TRA was attributed to decreased access site bleeding resulting in less hemoglobin drop and blood transfusion.

5. Correct modifiable risk factors for CI-AKI. Correct periprocedural hypovolemia, hypotension, hyperglycemia, anemia, and hold nephrotoxic drugs such as ACE inhibitors, NSAIDs, and ARBs.

6. Obtain follow up labs to diagnose CI-AKI and follow patients to ensure recovery of renal function.

7. Review benchmarked data. The PCI in-hospital risk adjusted acute kidney injury rate is a quality metric provided by the National Cardiovascular Data Registry (NCDR) CathPCI registry. Compare your institution’s data with national benchmarks.

Administration of oral N-acetyl cysteine and intravenous sodium bicarbonate do not offer any benefit based on a large randomized controlled trial and are no longer recommended.¹¹ In addition, isosmolar contrast does not seem to uniformly lower risk of CI-AKI compared to low-osmolar agents based on meta-analysis.¹² The 2009 focused update of the ACC/AHA guidelines for PCI recommends that the choice of contrast media be expanded to either isosmolar or low-osmolar contrast media other than ioxaglate or iohexol.¹³

Conclusion

While the incidence of CI-AKI in the average patient undergoing CA and PCI is low (~ 2%), patients with a combination of risk factors, such as pre-existing renal disease and diabetes, face a high risk. CI-AKI is strongly associated with increased mortality, health care costs, and progression of renal disease. Identification of high-risk patients and use of evidence-based measures can improve quality of care and outcomes in these patients.

References

1. Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1–138
2. Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. 2002;39(5):930-936.
3. Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004 Oct 6;44(7):1393-9.
4. Nikolsky E, Mehran R, Turcot D et al. Impact of chronic kidney disease on prognosis of patients with diabetes mellitus treated with percutaneous coronary intervention. Am J Cardiol. 2004;94:300–5.
5. Nikolsky E, Mehran R, Lasic Z et al. Low hematocrit predicts contrast-induced nephropathy after percutaneous coronary interventions. Kidney Int. 2005 Feb;67(2):706-13.
6. Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002 May 14;105(19):2259-64.
7. Brar SS, Aharonian V, Mansukhani P et al. Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial. Lancet. 2014;383:1814–23.
8. Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA, SCAI Guidelines for Percutaneous Coronary Intervention. Circulation. 2011;124:e574-e651.
9. Gurm HS, Dixon SR, Smith DE 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.
10. Andò G, Cortese B, Russo F et al; MATRIX Investigators. Acute Kidney Injury After Radial or Femoral Access for Invasive Acute Coronary Syndrome Management: AKI-MATRIX. J Am Coll Cardiol. 2017 May 11.
11. Weisbord SD, Gallagher M, Jneid H, et al. PRESERVE Trial Group. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018 Feb 15;378(7):603-614.
12. From AM, Al Badarin FJ, McDonald FS et al. Iodixanol versus low-osmolar contrast media for prevention of contrast induced nephropathy: meta-analysis of randomized, controlled trials. Circ Cardiovasc Interv. 2010 Aug;3(4):351-8.
13. Kushner FG, Hand M, Smith SC, et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction. Circulation. 2009;120:2271-2306.

Table 1. Risk factors for CI-AKI

Figure 1. Risk score to predict CI-AKI as described by Mehran et al. (3) Anemia- baseline hematocrit < 39 in men and < 38 in women, CHF- NYHA class III or IV, hypotension- systolic BP < 80 mmHg or requiring inotropic support for > 1 hour, IABP- elective or urgent and within 24 hours of procedure. Risk of requiring dialysis and one-year mortality rises steeply once score exceeds 16. eGFR is preferable to serum creatinine to assess renal function.