Incidence, Risk Factors, and Outcomes of Contrast Associated Nephropathy following Percutaneous Coronary Intervention

Iqbal Wani; Imran Hafeez; Aamir Rashid; Viqar Jan; Mohd Iqbal Dar; Hilal Rather; Khursheed Aslam; Usheem Syed

doi:10.4103/JCPC.JCPC_42_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 9 | Issue : 4 | Page : 145-149

Incidence, Risk Factors, and Outcomes of Contrast Associated Nephropathy following Percutaneous Coronary Intervention

Iqbal Wani MD, DM ¹, Imran Hafeez MD, DM ¹, Aamir Rashid MD DM MRCP UK ¹, Viqar Jan MD, DM ¹, Mohd Iqbal Dar MD, DM ¹, Hilal Rather MD, DM ¹, Khursheed Aslam MD, DM ¹, Usheem Syed MBBS ²
¹ Department of Cardiology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India
² Department of Medicine, SKIMS, Bemina, Srinagar, Jammu and Kashmir, India

Date of Submission	20-Jun-2020
Date of Decision	20-Jul-2020
Date of Acceptance	08-Oct-2020
Date of Web Publication	09-Feb-2021

Correspondence Address:
Dr. Aamir Rashid
Department of Cardiology, SKIMS, Soura, Srinagar, Jammu and Kashmir
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/JCPC.JCPC_42_20

Abstract

Introduction: Contrast-associated acute kidney injury (CA-AKI) is a prevalent but underdiagnosed complication of percutaneous coronary intervention (PCI) that is associated with increased inhospital morbidity and mortality. Aims and Objectives: The aims and objectives were to study the incidence, risk factors, and outcome of CA-KI following PCI. Materials and Methods: This was a single-center prospective observational study. Five hundred patients who were admitted in ward and medical intensive care unit with chronic stable angina and acute coronary syndrome (unstable angina, non-ST-elevation myocardial infarction [STEMI], and STEMI) for PCI (intracoronary stent implantation) were included in the present study. All baseline demographic and clinical characteristics including pre- and postprocedure kidney function test (24 h, 48 h) were noted. Hospital stay, need for dialysis, and mortality were recorded. Results: In this study, 500 patients were enrolled. The mean age of presentation was 61.83 ± 13.17 years. Three hundred and sixty-six patients (73.2%) were male. Of 500 patients, 52 (10.4%) patients developed AKI. AKI was significantly higher in those with diabetes (27.2% vs. 5.4% P < 0.001), heart failure (23.1% vs. 6.5% P < 0.001), left ventricular (LV) dysfunction (21.6% vs. 6.3% P < 0.001), peripheral vascular disease (24.5% vs. 8.9% P = 0.002), hypotension (42.6% vs. 5.2% P < 0.001), creatinine >1.2 (18.5% vs. 5.9% P < 0.001), lower creatinine clearance < 60 (25.4% vs. 5.8% P < 0.001), higher procedural time >60 min (20.2% vs. 7.3% P < 0.001), and higher contrast volume (302.7 ± 37.83 mL in AKI patients vs. and 173.2 ± 23.61 mL in no AKI patients P < 0.001). Multivariate logistic regression analysis showed Type 2 diabetes mellitus, heart failure, LV dysfunction, creatinine clearance <60, and contrast volume more than 270 mL to be significantly associated with the incidence of CA-AKI. AKI patients had significantly prolonged hospital stay as compared to those without AKI (9.2 ± 2.73 vs. 4.7 ± 1.79 days P < 0.001). Dialysis was required only in one (1.9%) patient. AKI patients had higher in hospital mortality as compared to non-AKI group (3 [5.8%] vs. 2 [0.4%] P = 0.004). Conclusion: The incidence of AKI after PCI in our study was 10%. Patients having diabetes, heart failure, LV dysfunction, estimated creatinine clearance, and higher contrast volume were found to be at highest risk. Appropriate preventive measures should be taken in these high-risk patients to avoid adverse outcomes associated with contrast-induced nephropathy.

Keywords: Contrast-induced nephropathy, coronary artery disease, percutaneous coronary intervention

How to cite this article:
Wani I, Hafeez I, Rashid A, Jan V, Dar MI, Rather H, Aslam K, Syed U. Incidence, Risk Factors, and Outcomes of Contrast Associated Nephropathy following Percutaneous Coronary Intervention. J Clin Prev Cardiol 2020;9:145-9

How to cite this URL:
Wani I, Hafeez I, Rashid A, Jan V, Dar MI, Rather H, Aslam K, Syed U. Incidence, Risk Factors, and Outcomes of Contrast Associated Nephropathy following Percutaneous Coronary Intervention. J Clin Prev Cardiol [serial online] 2020 [cited 2023 Feb 6];9:145-9. Available from: https://www.jcpconline.org/text.asp?2020/9/4/145/308977

Introduction

Contrast-associated acute kidney injury (CA-AKI) is commonly prevalent but underdiagnosed complication of percutaneous coronary intervention (PCI) that is associated with increased inhospital morbidity and mortality.^{[1],[2],[3],[4],[5]} Patients undergoing PCI are at risk of several complications, the most common of which is CA-AKI.^[2] CA-AKI is defined as an increase in serum creatinine concentration of > 0.5 mg/dl (>44 μmol/L) or 25% above baseline within 48 h after contrast administration.^[6] The pathophysiology of CA-AKI includes an increase in vasoconstriction, cytotoxicity, and higher viscosity of contrast leading to ischemia and acute tubular injury.^[4] Incidence of CA-AKI can vary between 2% in low-risk populations to more than 50% in high-risk patients.^[7] It is associated with several adverse outcomes including an increased need for hemodialysis, persistent decline in renal function, increased mortality,^[1],[7] extended inpatient care period, and increased costs of care.^[8],[9],[10] The factors that increase risk of CA AKI are chronic kidney disease, volume and type of contrast media used, diabetes, congestive heart failure (CHF), higher age, anemia, and decreased circulating blood volume.^{[11],[12],[13],[14]}

Various research scores have been developed for predicting CA-AKI; however, they have not been adequately validated.^[7] Mehran score has also been questioned recently and CA-AKI consensus working panel does not recommend it for CA-AKI prediction.^[15] The current study was designed to study the incidence, risk factors, and outcome of patients who develop CA-AKI. This would, in turn, help in identifying the most susceptible population in whom appropriate measures can be taken to reduce the development of CA-AKI and decrease the associated morbidity and mortality.

Aims and objectives

To determine the incidence and risk factors of contrast-induced nephropathy (CIN) after PCI
To analyze the outcome including mortality, the need of dialysis, and impact on the length of hospital stay of CA-AKI.

Materials and Methods

Study design

This prospective observational study was conducted in the Department of Cardiology, Sheri-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India. All patients admitted in the cardiology ward or intensive care unit for a period of 2 years from April 2016 to April 2018 who required PCI were screened for the eligibility criteria.

Inclusion criteria

All patients who were admitted and underwent PCI (intracoronary stent implantation) during the study period whether for chronic stable angina or acute coronary syndrome (unstable angina, non-ST-elevation myocardial infarction [NSTEMI] and ST-elevation myocardial infarction [STEMI]) were included in the study.

Exclusion criteria

Patients who denied consent for the procedure, patients with preoperative Azotemia (serum creatinine levels >1.5 mg/dl.), intravascular administration of contrast medium within previous 7 days, history of reaction to the contrast medium, renal transplantation or end-stage renal disease necessitating dialysis, intake of nephrotoxic drugs within previous 7 days, patients who developed PCI related complications, patients with cardiogenic shock, and patients requiring Intraaortic balloon pump (IABP) support.

All admitted patients underwent blood sampling for baseline hematological and biochemical parameters. Creatinine was repeated at 24 and 48 h post procedure during the hospital stay. Most of the patients received hydration with normal saline 6 h pre and post procedure. Creatinine clearance was calculated using Cockcroft–Gault equation. CI-AKI was defined as an increase in serum creatinine concentration of >0.5 mg/dl (>44 μmol/L) or 25% above baseline within 48 h after contrast administration.

Statistical methods

The recorded data were compiled and entered in a spreadsheet (Microsoft Excel) and then exported to data editor of SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean ± standard deviation (SD) and categorical variables were summarized as frequencies and percentages. Student's independent t-test was employed for comparing continuous variables. Chi-square test or Fisher's exact test, whichever appropriate, was applied for comparing categorical variables. P < 0.05 was considered statistically significant.

Results

A total of 630 patients were screened. One hundred and thirty patients were excluded (baseline creatinine >1.5 in 50, renal transplantation or end-stage renal disease necessitating dialysis in 10, denied consent for the procedure in 50, intravascular administration of contrast medium within previous 7 days in 9, and history of reaction to contrast medium in 11). Five hundred patients were enrolled. The mean age of presentation was 61.83 ± 13.17 years. Three hundred and sixty-six patients (73.2%) were male and 134 (26.8%) were female. Baseline serum creatinine was 1.01 ± 0.41 mg/dl.

Incidence and risk factors

Of 500 patients, 52 (10.4%) patients developed CA-AKI. CA-AKI was significantly higher in those with diabetes (27.2% vs. 5.4% P < 0.001), heart failure (23.1% vs. 6.5% P < 0.001), left ventricular (LV) dysfunction (21.6% vs. 6.3% P < 0.001), peripheral vascular disease (PVD) (24.5% vs. 8.9% P = 0.002), hypotension (42.6% vs. 5.2% P < 0.001), creatinine > 1.2 (18.5% vs. 5.9% P < 0.001), lower creatinine clearance < 60 (25.4% vs. 5.8% P < 0.001), and higher procedural time > 60 min (20.2% vs. 7.3% P < 0.001) [Table 1]. The mean ± SD of contrast volume was 302.7 ± 37.83 mL in CIN patients and 173.2 ± 23.61 mL in no CIN patients with significant (P < 0.001) [Table 2]. Four hundred and ninety-seven patients received contrast medium iohexol and only in three patients, Iodixanol was used. In our study of 500 patients, of total of 52 AKI patients, 44 (84.6%) patients had Stage I AKI, 6 (11.5%) patients had Stage II AKI, and only 2 (3.8%) patients developed Stage III AKI (KDIGO Staging). Highest number of patients (20.9%) with AKI was seen in the age group of 70–79 years, followed by 13.2% in the age group of 60–69 years. No patient with AKI was seen in 30–39 years, whereas only one (2.4%) patient developed AKI in the age group of 40–49 years (P = 0.016) [Table 3]. There was no statistically significant difference in males versus females (9.6% vs. 12.7% P = 0.3) or hypertensives versus nonhypertensives (13.3% vs. 9.6% P = 0.25). Multivariate logistic regression analysis showed Type 2 diabetes mellitus, heart failure, LV dysfunction, creatinine clearance <60, and contrast volume more than 270 mL to be significantly associated with incidence of CA-AKI [Table 4].

Table 1: Risk factors associated with acute kidney injury

Click here to view

Table 2: Relationship of contrast volume with acute kidney injury

Click here to view

Table 3: Incidence of acute kidney injury as per age among the study patients

Click here to view

Table 4: Multivariate logistic regression analysis of risk factors for acute kidney injury

Click here to view

Outcome

AKI patients had significantly prolonged hospital stay as compared to those without AKI (9.2 ± 2.73 vs. 4.7 ± 1.79 days P < 0.001). Dialysis was required only in one (1.9%) patient. AKI patients had higher inhospital mortality (3 [5.8%] vs. 2 [0.4%] P = 0.004). The cause of death in the AKI patients was sudden cardiac arrest due to Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) in two patients, while the third one developed sepsis and died of septic shock.

Discussion

The present prospective study was conducted on 500 patients who were admitted with chronic stable angina and acute coronary syndrome (unstable angina, NSTEMI, and STEMI) for PCI in our department over a period of 2 years.

Incidence of acute kidney injury

In our study of 500 patients, 52 (10.4%) patients developed AKI which is comparable to other studies.^{[16],[17],[18],[19],[20],[21],[22],[23]} The incidence of CA-AKI varies from 2% in low-risk populations to more than 50% in high-risk patients.^[7] The difference in the reported incidence of CA-AKI in different studies is likely due to the different inclusion and exclusion criteria. Our study showed a higher incidence of 10.4% as compared to Kumar et al.^[24] who reported an incidence of 2.4%. Their low incidence is because they excluded patients with hypotension and acute myocardial infarction which were included in our study. On the other hand, Valappil et al.^[25] reported an incidence of 29% as they included patients with impaired estimated glomerular filtration rate (30–60 mL/min/1.73 m²). The mean age of presentation was 61.3 ± 13.87 years which is comparable to other studies.^{[16],[18],[20],[26]} Three hundred and sixty-six patients (73.2%) were male and 134 (26.8%) were female with a male-to-female ratio of 2.7:1.

Risk factors

The risk factors that were significantly associated with CA-AKI in univariate analysis were diabetes, heart failure, LV dysfunction, PVD, hypotension, creatinine >1.2, lower creatinine clearance <60 mL/min, higher procedural time >60 min, higher contrast volume, and increasing age.

Among diabetics, 27% developed CA-AKI as compared to 5% nondiabetics. Association of diabetes with CA-AKI has also been shown in other studies.^{[16],[17],[27]} Diabetes predisposes to CA-AKI, especially in those with renal functional impairment. Renal hypoxia and reactive oxygen species also play a major role in the pathogenesis of CIN, and the diabetic kidney is susceptible to intensified hypoxic and oxidative stress after administration of contrast media. The pathophysiology involves various mechanisms, including a prior enhanced tubular transport activity, oxygen consumption, and the generation of reactive oxygen species. Both micro- and macrovascular diseases and chronic tubulointerstitial changes further reduce regional oxygen delivery, and renal antioxidant capacity might be hampered. A better understanding of these mechanisms and their control in the diabetic patient may initiate novel strategies in the prevention of contrast nephropathy in these patients.

Twenty-seven (23.1%) patients with heart failure developed AKI as opposed to 25 (6.5%) patients without heart failure. This is consistent with other data.^{[28],[29],[30],[31]} CIN was also found to be significantly associated with LV systolic dysfunction (21.6% vs. 6.3% P < 0.001). CHF and decreased LV function are established risk factors for the development of CA-AKI. Radiocontrast causes renal vasoconstriction and medullary hypoxia. However, in animal models, contrast alone is insufficient to cause toxicity, and a second insult, such as salt depletion or CHF, is also required. These states of decreased effective blood volume lead to an increase in sympathetic activity, increased vasopressin release, and renin–angiotensin activation, which may all contribute to medullary hypoxia.

Twelve (24.5%) patients with PVD developed AKI compared with 40 (8.9%) in those without PVD which is consistent with various studies.^[29],[32] Since inflammation and oxidative stress are integral components of the pathogenesis of peripheral arterial disease, it may further contribute to AKI following contrast administration.

Twenty-nine (42.6%) patients with hypotension developed AKI compared with 23 (5.2%) in those without hypotension. Hypotension predisposes to CA-AKI.^[17],[32] The mechanisms of AKI may be related to renal hemodynamic instability with renal hypoperfusion with hypotension.

We also noted that CIN was significantly higher in those with increasing age. No patient with age <40 years developed AKI, whereas highest AKI was seen in those above 70 years age. Other authors have reported similar results.^{[17],[31],[32]}

Among AKI patients, 57% had creatinine clearance <60% compared to only 19% in non-AKI group (P < 0.001). The contrast volume was significantly higher in AKI versus no AKI patients (302.7 ± 37.83 mL vs. 173.2 ± 23.61 mL P = 0.001). Limiting the volume of contrast as much as possible is recommended. The best way to prevent CA-AKI is to identify patients at high risk and provide adequate volume administration. Similar results have been reported by other authors.^{[16],[31],[32]}

Outcome

CA-AKI patients had prolonged hospital stay as compared to those without CA-AKI (mean ± SD was 9.2 ± 2.73 vs. 4.7 ± 1.79 days; P < 0.001). Other authors have reported similar results.^{[17],[26],[32]} Dialysis was required only in one (1.9%) patient. Three (5.8%) patients died in AKI group, whereas only 2 (0.4%) patients died in no AKI group (P = 0.004). Higher mortality in CA-AKI patients has been reported by other authors.^[29],[32]

Limitations

It was a single-center study. Renal functions were monitored only up to 48 h after PCI and not after that which could have underestimated the incidence of CA-AKI. Long-term follow-up of patients who developed CIN was not done.

Conclusion

The incidence of AKI after PCI in our study was 10%. Patients having diabetes, increasing age, heart failure, LV dysfunction, PVD, hypotension, and lower estimated creatinine clearance are at the highest risk. Appropriate preventive measures should be taken in these high-risk patients to avoid adverse outcomes associated with CA-AKI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Blackman DJ, Pinto R, Ross JR, Seidelin PH, Ing D, Jackevicius C, et al. Impact of renal insufficiency on outcome after contemporary percutaneous coronary intervention. Am Heart J 2006;151:146-52.
2.	Lindsay J, Apple S, Pinnow EE, Gevorkian N, Gruberg L, Satler LF, et al. Percutaneous coronary intervention-associated nephropathy foreshadows increased risk of late adverse events in patients with normal baseline serum creatinine. Catheter Cardiovasc Interv 2003;59:338-43.
3.	McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F. Epidemiology and prognostic implications of contrastinduced nephropathy. Am J Cardiol 2006;98:5K-13.
4.	Sushrut SW, Joseph VB. Acute Kidney Injury. Harrison's Principles of Internal Medicine. Vol. II., 18^th ed.. New York: McGraw-Hill Medical Publishing Division; 2011. p. 2293-308.
5.	Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
6.	Tepel M, Aspelin P, Lameire N. Contrast-induced nephropathy: A clinical and evidence-based approach. Circulation 2006;113:1799-806.
7.	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;44:1393-9.
8.	Fishbane S, Durham JH, Marzo K, Rudnick M. N-acetylcysteine in the prevention of radiocontrast-induced nephropathy. J Am Soc Nephrol 2004;15:251-60.
9.	Goldenberg I, Matetzky S. Nephropathy induced by contrast media: Pathogenesis, risk factors and preventive strategies. CMAJ 2005;172:1461-71.
10.	Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A cohort analysis. JAMA 1996;275:1489-94.
11.	Nough H, Eghbal F, Soltani M, Nejafi F, Falahzadeh H, Fazel H, et al. Incidence and main determinants of contrast-induced nephropathy following coronary angiography or subsequent balloon angioplasty. Cardiorenal Med 2013;3:128-35.
12.	Baker CS, Wragg A, Kumar S, de Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: The RAPPID study. J Am Coll Cardiol 2003;41:2114-8.
13.	Diaz-Sandoval LJ, Kosowsky BD, Losordo DW. Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial). Am J Cardiol 2002;89:356-8.
14.	Drager LF, Andrade L, Barros de Toledo JF, Laurindo FR, Machado César LA, Seguro AC. Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: Decrease in oxidant stress-mediated renal tubular injury. Nephrol Dial Transplant 2004;19:1803-7.
15.	Tumlin J, Stacul F, Adam A, Becker CR, Davidson C, Lameire N, et al. Pathophysiology of contrast-induced nephropathy. Am J Cardiol 2006;98:14K-20.
16.	Alam AB, Moniruzzaman M, Alam MB, Islam N, Khatoon F, Hahan N, et al. Assessment of acute kidney injury in patients undergoing elective coronary angiography and percutaneous coronary intervention. Cardiovasc. J. 2012;5:37-43.
17.	He F, Zhang J, Lu ZQ, Gao QL, Sha DJ, Pei LG, et al. Risk factors and outcomes of acute kidney injury after intracoronary stent implantation. World J Emerg Med 2012;3:197-201.
18.	Sharma SL, Dubey L, Laudary S, Dhunge S, Ghimire M, Pahari B, et al. Incidence and predictors of contrast induced nephropathy after coronary intervention at college of medical sciences teaching hospital, Bharatpur. Nepalese Heart J 2014;11:3-11.
19.	Taher HS, Hassan AK, Dimitry SR, Mahfouz AK. Predicting contrast induced nephropathy post coronary intervention: A prospective cohort study. Egypt Heart J 2015;67:337-43.
20.	Shacham Y, Leshem-Rubinow E, Gal-Oz A, Arbel Y, Keren G, Roth A, et al. Acute cardio-renal syndrome as a cause for renal deterioration among myocardial infarction patients treated with primary percutaneous intervention. Can J Cardiol 2015;31:1240-4.
21.	Assareh A, Yazdankhah S, Majidi S, Nasehi N, Beladi Mousavi SS. Contrast induced nephropathy among patients with normal renal function undergoing coronary angiography. J Renal Inj Prev 2016;5:21-4.
22.	Farhan S, Vogel B, Tentzeris I, Jarai R, Freynhofer MK, Smetana P, et al. Contrast induced acute kidney injury in acute coronary syndrome patients: A single centre experience. Eur Heart J Acute Cardiovasc Care 2016;5:55-61.
23.	Pérez-Topete SE, Miranda-Aquino T, Gasca-Luna K, Guerra-Villa MN, Elizondo-Adamchik HE. Contrast-induced nephropathy in patients undergoing percutaneous coronary intervention. Rev Mex Cardiol 2016;27:64-70.
24.	Kumar S, Nair RK, Aggarwal N, Abbot AK, Muthukrishnan J, Kumar KV. Risk factors for contrast-induced nephropathy after coronary angiography. Saudi J Kidney Dis Transpl 2017;28:318-24. [PUBMED] [Full text]
25.	Valappil SP, Kunjukrishnapillai S, Iype M, Koshy AG, Viswanathan S, Gupta PN, et al. Predictors of contrast induced nephropathy and the applicability of the Mehran risk score in high risk patients undergoing coronary angioplasty A study from a tertiary care centre in South India. Indian Heart J 2017;1279:1-6.
26.	Kashif W, Khawaja A, Yaqub S, Hussain SA. Clinically significant contrast induced acute kidney injury after non-emergent cardiac catheterization Risk factors and impact on length of hospital stay. J Coll Physicians Surg Pak 2013;23:842-7.
27.	Dutta PK, Mannan MM. Risk factors of contrast induced acute kidney injury A single centre study in Tertiary hospital of Bangladesh. Asian J Sci Technol 2015;6:1080-2.
28.	Shoukat S, Gowani SA, Jafferani A, Dhakam SH. Contrast-induced nephropathy in patients undergoing percutaneous coronary intervention. Cardiology Research and Practice 2010;6:1080-2.
29.	Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;105:2259-64.
30.	Tehrani S, Laing C, Yellon DM, Hausenloy DJ. Contrast-induced acute kidney injury following PCI. Eur J Clin Invest 2013;43:483-90.
31.	Tsai TT, Patel UD, Chang TI, Kennedy KF, Masoudi FA, Matheny ME, et al. Validated contemporary risk model of acute kidney injury in patients undergoing percutaneous coronary interventions: Insights from the National Cardiovascular Data Registry Cath-PCI Registry. J Am Heart Assoc 2014;3:e001380.
32.	Victor SM, Gnanaraj A, Vijaya Kumar S, Deshmukh R, Kandasamy M, Janakiraman E, et al. Risk scoring system to predict contrast induced nephropathy following percutaneous coronary intervention. Indian Heart J 2014;66:517-24.