Prediction of Persistent Renal Dysfunction Following Contrast-Induced Nephropathy After Cardiac Catheterization Procedures

Contrast-induced nephropathy (CIN), recognized as acute kidney injury (AKI) after contrast medium exposure, has been identified as the most frequent cause of hospital-acquired AKI.¹ This iatrogenic complication has been a subject of concern for cardiologists in recent years because CIN is associated with increased morbidity and mortality^2,3 after cardiac catheterization procedures such as coronary angiography and percutaneous coronary intervention (PCI). CIN is generally considered transient, with serum creatinine (SCr) levels typically reaching the peak in a few days and returning to baseline within 2 weeks in most cases.⁴ However, some patients with CIN develop a persistent increase in SCr levels.

Article p ????

Some studies have investigated the prognostic impact of transient or persistent renal dysfunction (RD) after development of CIN.^4,5 These studies reported that persistent RD is associated with significantly higher long-term mortality than transient RD and is independently associated with worse clinical outcomes. Although CIN itself is associated with worse clinical outcomes, there is a strong association between persistent RD after development of CIN and worse clinical outcomes. Thus, the reversibility of RD after development of CIN has significant implications for long-term follow-up of patients who undergo cardiac catheter procedures.

Although several risk scores are available as predictors of CIN after cardiac catheterization procedures,² little is known about the predictors of persistent RD. The Mehran risk score is widely used for predicting CIN,⁶ and it includes 8 clinical and procedural variables, including age >75 years, hypotension, anemia, congestive heart failure, intra-aortic balloon pumping, preprocedural renal function, diabetes mellitus, and contrast volume. Maioli et al⁴ reported that Mehran risk score ≥17 is an independent predictor of persistent RD. Wi et al⁷ reported that high risk (Mehran risk score of 11–15) and very high risk (Mehran risk score ≥16) is an independent predictor of persistent RD in patients with acute myocardial infarction (AMI) undergoing PCI. Several studies reported that change in SCr within 12 h or a few days after cardiac catheterization procedures can predict persistent RD.^4,8,9 The change in urine neutrophil gelatinase-associated lipocalin, an early biomarker of AKI, has also been reported as a useful biomarker for persistent RD.⁹ The use of a greater volume of contrast media has been found to increase the risk of CIN in patients undergoing cardiac catheterization procedures.² Kurogi et al¹⁰ reported that contrast volume/baseline estimated glomerular filtration rate (eGFR) ratio >3.45 is independently associated with the development of persistent RD. This ratio has a similar predictive value as the Mehran risk score. These clinical studies of the incidence and predictors of persistent RD after CIN are summarized in the Table, and they suggest that patients at higher risk of developing CIN are also more likely to have persistent RD.

Table. Incidence and Predictors of Persistent Renal Dysfunction After Contrast-Induced Nephropathy

Study	Year	Definition of persistent RD in patients with CIN	Incidence of persistent RD among patients with CIN	Predictors of persistent RD
Ribichini et al8	2010	Reduction in eGFR ≥25% from baseline at 30 days	38.5% of 39 patients with CIN	5–10% increase in SCr above baseline at 12 h
Maioli et al4	2012	Reduction in creatinine clearance ≥25% from baseline at 3 months	18.6% of 167 patients with CIN	Mehran risk score ≥17, LVEF ≤30%, or 1.5-fold increase in SCr from baseline within 5 days
Wi et al7	2013	Increase in SCr ≥0.5 mg/dL or ≥25% from baseline at 1 month	45.9% of 148 patients with CIN	High (11–15) or very high (≥16) risk group based on the Mehran risk score
Briguori et al9	2018	Increase in SCr ≥0.3 mg/dL from baseline at 1 month	26% of 118 patients with CIN	Urinary NGAL ≥0.50 ng/dL at 48 or absolute SCr increase ≥0.2 mg/dL between 48 and 72 h
Kurogi et al10	2019	Increase in SCr ≥0.5 mg/dL or ≥25% from baseline over 2 weeks	34.5% of 84 patients with CIN	Contrast volume/eGFR ratio >3.45
Luo et al11	2022	Increase in SCr ≥0.5 mg/dL or ≥25% over baseline at 1 week to 12 months	7.3% of 550 patients with CIN	NT-proBNP >876.1 pg/mL at baseline

CIN, contrast-induced nephropathy; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; NGAL, neutrophil gelatinase-associated lipocalin; NT-proBNP, N-terminal pro B-type natriuretic peptide; RD, renal dysfunction; SCr, serum creatinine.

In this Issue of the Journal, Luo et al¹¹ prospectively examine the value of preprocedural N-terminal pro B-type natriuretic peptide (NT-proBNP) for predicting persistent RD, which is described as CIN non-recovery, in 550 patients with CIN after PCI. They demonstrated that NT-proBNP >876.1 pg/mL, which was the best cutoff vale for predicting persistent RD, is an independent predictor of persistent RD. NT-proBNP >876.1 pg/mL and persistent RD were significantly associated with long-term mortality in patients who developed CIN. A previous study suggested that BNP or NT-proBNP might be an effective marker for predicting CIN.¹² To the best of their knowledge, this is the first study to investigate the association between NT-proBNP levels and persistent RD. It defined persistent RD as a persistent increase of SCr >25% or 0.5 mg/dL above baseline at three time points (1 week, 3 months and 12 months) after discharge. The time intervals for assessing persistent RD in this study were longer than in other studies (Table). The definition of persistent RD used in this study might identify a population with confirmed long-term worsening of renal function after PCI. Some patients classified as having persistent RD early on might have later improvement in renal function, which might explain why the incidence of persistent RD in this study (7.3%) was lower than in other studies (18.6–45.9%).

The mechanisms underlying the association between NT-proBNP and persistent RD remain unclear, but might include the following. First, NT-proBNP reflects impaired cardiac output and increased venous congestion, such as with AMI and congestive heart failure, which lead to systemic and renal hemodynamic changes that can result in persistent RD. Second, NT-proBNP is related to risk factors for the progression from AKI to chronic kidney disease (CKD), such as age, diabetes mellitus, proteinuria, and pre-existing CKD.¹³ Third, NT-proBNP might be an indicator of increased inflammation,¹⁴ which plays an important role in the development of persistent RD. Luo et al show that patients with higher NT-proBNP were more likely to be older and have diabetes mellitus, AMI, chronic heart failure, reduced left ventricular ejection fraction, and decreased eGFR. Therefore, the cutoff value of NT-proBNP >876.1 pg/mL might reflect the influence of multiple comorbidities and the systemic and renal hemodynamics associated with the development of persistent RD.

Several studies have demonstrated that patients with persistent RD have worse clinical outcomes than those with transient RD. Therefore, it is important to identify persistent RD as early as possible for risk stratification of patients with CIN. In patients at high risk of developing persistent RD after CIN, early clinical follow-up, careful management, and close monitoring of renal function might improve long-term clinical outcomes. Currently, once CIN develops, there is no effective treatment to prevent persistent RD, only waiting for recovery of renal function. Effective treatments for preventing persistent RD in patients with CIN need to be developed in future studies.

Disclosures

None.

IRB Information / Reference Number

Not applicable.

References

• 1.   McCullough PA. Contrast-induced acute kidney injury. J Am Coll Cardiol 2008; 51: 1419–1428.
• 2.   Isaka Y, Hayashi H, Aonuma K, Horio M, Terada Y, Doi K, et al; Japanese Society of Nephrology; Japan Radiological Society; Japanese Circulation Society Joint Working Group. Guideline on the use of iodinated contrast media in patients with kidney disease 2018. Circ J 2019; 83: 2572–2607.
• 3.   Sato A, Aonuma K, Watanabe M, Hirayama A, Tamaki N, Tsutsui H, et al. Association of contrast-induced nephropathy with risk of adverse clinical outcomes in patients with cardiac catheterization: From the CINC-J study. Int J Cardiol 2017; 227: 424–429.
• 4.   Maioli M, Toso A, Leoncini M, Gallopin M, Musilli N, Bellandi F. Persistent renal damage after contrast-induced acute kidney injury: Incidence, evolution, risk factors, and prognosis. Circulation 2012; 125: 3099–3107.
• 5.   Abe M, Morimoto T, Nakagawa Y, Furukawa Y, Ono K, Kato T, et al. Impact of transient or persistent contrast-induced nephropathy on long-term mortality after elective percutaneous coronary intervention. Am J Cardiol 2017; 120: 2146–2153.
• 6.   Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, 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; 44: 1393–1399.
• 7.   Wi J, Ko YG, Shin DH, Kim JS, Kim BK, Choi D, et al. Prediction of contrast-induced nephropathy with persistent renal dysfunction and adverse long-term outcomes in patients with acute myocardial infarction using the Mehran risk score. Clin Cardiol 2013; 36: 46–53.
• 8.   Ribichini F, Graziani M, Gambaro G, Pasoli P, Pighi M, Pesarini G, et al. Early creatinine shifts predict contrast-induced nephropathy and persistent renal damage after angiography. Am J Med 2010; 123: 755–763.
• 9.   Briguori C, Quintavalle C, De Micco F, Visconti G, Di Palma V, Napolitano G, et al. Persistent serum creatinine increase following contrast-induced acute kidney injury. Catheter Cardiovasc Interv 2018; 91: 1185–1191.
• 10.   Kurogi K, Ishii M, Sakamoto K, Komaki S, Marume K, Kusaka H, et al. Persistent renal dysfunction in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. J Am Heart Assoc 2019; 8: e014096.
• 11.   Luo M, Zhu Z, Zhang L, Zhang S, You Z, Chen H, et al. Predictive value of N-terminal pro B-type natriuretic peptide for contrast-induced nephropathy non-recovery and poor outcomes among patients undergoing percutaneous coronary intervention. Circ J, doi:10.1253/circj.CJ-22-0399.
• 12.   Li X, Liu C, Mao Z, Qi S, Song R, Zhou F. Brain natriuretic peptide for predicting contrast-induced acute kidney injury in patients with acute coronary syndrome undergoing coronary angiography: A systematic review and meta-analysis. J Interv Cardiol 2020; 2020: 1035089.
• 13.   Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371: 58–66.
• 14.   Jensen J, Ma LP, Fu ML, Svaninger D, Lundberg PA, Hammarsten O. Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio. Clin Res Cardiol 2010; 99: 445–452.