Contrast-Induced Nephropathy Among Patients Undergoing Cardiac Catheterization

Contrast-induced nephropathy is an important complication after cardiac catheterization, and is associated with accelerated renal disease, increased costs, mortality rate, need for dialysis and prolonged hospital stay. This study aim is to find its incidence and risk factors. It is a cross-sectional study on 160 patients admitted for diagnostic or therapeutic percutaneous coronary intervention in Basra Cardiac Center, from March to September 2016. Data collected were a complete history, examination, blood pressure, Echo study, fasting blood sugar, lipid profile, blood urea, serum creatinine and estimated glomerular filtration rate, the type and duration of procedure, volume of contrast, and after 48 hours renal function tests were repeated. Contrast-induced nephropathy has developed in 7 (8.3%) men and 5 (6.6%) women; 11 (10.8%) from 102 patients with dyslipidemia (P = 0.03); 8 (22.2%) from 36 with preexisting renal impairment (P = 0.01); 11 (10.9%) from 101 with hypertension (P = 0.02); 9 (13.6%) from 66 diabetic (P = 0.016); 9 (17.3%) from 52 smoker (P = 0.002); 4 (23.5%) from 17 alcohol drinkers (P = 0.026); 11 (11.2%) from 98 with ischemic heart disease (P = 0.02); and 9 (25.7%) from 35 with heart failure (P = <0.001). Also found in 1 (1.6%) from 64 diagnostic procedures; 11 (11.5%) from 96 therapeutic procedures (P = 0.016); 5 (3.7%) from 135 patients received < 300 ml of contrast; and 7 (28%) from 25 received ≥ 300 ml (P = 0.001). In conclusion contrast-induced nephropathy is aggravated by increasing age, diabetes mellitus, heart failure, ischemic heart disease, renal impairment, hypertension, dyslipidemia, smoking and alcohol use. The type of procedure (therapeutic vs. diagnostic), and large volume of contrast agent are important risk factors. Gender had no significant effect.


Introduction
Contrast-induced nephropathy (CIN) is defined as an absolute (≥ 0.5mg/dL) or relative increase (≥ 25%) in serum creatinine at 48-72h after exposure to a contrast agent compared to baseline serum creatinine level, after exclusion of alternative explanation of renal impairment [1]. The incidence of CIN among the general population was found to be (1% -6%), and increases by 20% or more in selected patients, especially those with previous history of cardiovascular disease [1,2]. CIN is the third most common cause of renal impairment acquired in hospitals after renal perfusion impairment and nephrotoxic drugs [3]. It is associated with accelerated development of end-stage renal disease, increased costs, mortality rate, need for dialysis and prolonged hospital stay [4]. CIN normally is transient and the renal function return to baseline within 5-7 days after exposure to contrast agent, less than one third of patients will develop residual renal impairment and dialysis is required in less than 1% of them. The mortality rate in patients with preexisting renal impairment rising to 17% while the rate is around 3.9% without preexisting renal impairment [5]. The pathogenesis of CIN is not so clear, but it is thought to be due to acute tubular necrosis caused by renal vasoconstriction and direct cytotoxicity to the renal tubular epithelium [6]. Many experimental and clinical studies suggest that the osmolality of contrast agent may play a role in the development of CIN [7].
There are many risk factors for CIN development divided into non modifiable and modifiable, and can be either patient related or procedure related. Older age, diabetes mellitus, preexisting renal failure, and heart failure have all been identified as important risk factors for developing CIN [5,8,9]. On the other hand, the main modifiable risk factor is the volume of contrast media. The risk of CIN was minimal in patients who received a contrast volume of 100 mL or less, although, in the presence of other risk factors even low dose of contrast can cause permanent renal failure especially in patient with underlying renal disease [10]. Other properties of contrast media such as viscosity and ionicity may also share the same risk for CIN [11]. Many medications such as NSAID, diuretics, aminoglycosides, metformin and vancomycin can affect renal function through many mechanisms, so withholding these medications is considered before contrast exposure [2]. The major preventive measure is the intravenous volume expansion before contrast agent administration (0.45% or 0.9% saline, 100 ml/h, 12 hours before and 12 hours after) [12,38]. The effectiveness of sodium bicarbonate and N-acetylcysteine in CIN prevention is controversial, and there are no recommendations to use them due to insufficient evidence of its efficacy [13,14]. Statins were studied as potential agents to prevent CIN; one of these studies found a significant reduction in CIN incidence, and better post-procedural creatinine clearance [15]. However, till now there is no overall substantial evidence to support the use of statins before contrastenhanced interventions [11,40]. Regarding the use of prophylactic hemodialysis after contrast exposure, there was no benefit of it as shown by three studies [16]. On the other hand, prophylactic hemofiltration appears to be effective in preventing CIN and is associated with improvement of in-hospital and long-term outcomes [17]. The aim of this study is to find the frequency of CIN among patients undergoing coronary catheterization, and its risk factors.

Patients and Methods
A cross-sectional study was carried out on 160 patients {85 male (53.1%), 75 female (46.9%)}, who underwent diagnostic and/or therapeutic PCI, between March 2016 and September 2016, in Basra cardiac center. The inclusion criteria were: age more than 18 years, not on nephrotoxic drugs, and had no acute illness or advanced chronic kidney disease. The exclusion criteria were: the patients who refused to consent, patients who did not have renal function test at the day of the procedure or 48 hours after it, and patients who had other cause for renal impairment.
Before the procedure full history and physical examination elicited. Blood pressure and Echo study results were recorded. Blood sample was taken for serum creatinine, fasting plasma glucose, and lipid profile estimation. GFR was calculated by the CKD-EPI Creatinine 2009 equation [18]. After the procedure, the type and duration of the procedure and the volume of administered contrast agent were recorded, and after 48 hours renal function tests were repeated for each patient. The contrast agent that was used in all procedures was Ultravist® (Bayer Health Care / Germany), each 1 ml contains Iopromide 0.769 g (370mg Iodine/ml). Table 1 shows the characteristics of the patients and of the studied variables.

Discussion
In this study, the incidence of CIN was 7.5% in patients who underwent coronary interventional procedures, which is similar to other studies [2,27]. This result was lower than the study by Pérez-Topete et al in which the incidence was 14.2 % [8]. Also our result is higher than that shown by Rihal et al that was only 3.3 % [5]. This can be due to use of prophylactic measures before the procedure and sample size of each study. The presence of CIN shown to be significantly increased with increasing age of the patient with prevalence increased from (2.1%) in patients under 45 years old to (16%) in patients above 65 years old. This result was similar to other studies, and it is due to many factors including reduction of GFR and decrease in renal tubular function and concentration ability [10,28]. Gender had no significant effect on the incidence of CIN; (8.3%) in males and (6.6%) in females. This is supported by other studies like that by Marenzi et al [29]. Hypertension has significantly increased the risk of CIN, and this can be due to effect of high blood pressure on the arteries around the kidneys which lead to vasospasm, narrowing and hardening of these arteries, and this is similar to a study by Bartholomew et al [30]. There was significant increase in CIN prevalence in diabetic patients (13.6%), and this result supported by other studies that show incidence of CIN between 5.7 % -29.4%, mainly due to the decrease in GFR and multiple vascular complications in these patients [31,35]. dyslipidemia significantly increased the risk of CIN, this was supported by the study of Liu et al who studied 3632 patients. This is because LDL-C is associated with endothelial dysfunction, inflammation, and vasoconstriction, which are involved in the pathophysiology of CIN [32].
Preexisting HF shown to significantly increase the risk of CIN development in this study, which can be due to low renal perfusion [5,30,33]. IHD also was significantly increased the incidence rate of CIN in this study, since 11 out of the12 patients who developed CIN had a history of IHD, sharing the same underlying mechanism with HF that lead to reduced renal perfusion [34,35]. This study show significant association between preexisting renal impairment and prevalence of CIN, prevalence of CIN after PCI was increased with decreasing GFR [36]. Smoking also significantly increased the frequency of CIN in this study, because smoking can increase blood pressure, activation of the sympathetic nerve, the renin-angiotensin, and the endothelin systems as well as alteration of intra renal hemodynamics [37]. This result differs from other study which found that smoking was not a significant risk factor for CIN development [30].
Type of the procedure was also important. Therapeutic procedure significantly increases the prevalence of CIN development more than diagnostic procedure. This can be attributed to the volume of contrast agent in these procedures, as therapeutic intervention take longer duration that needs larger volume of contrast agent; this is supported by a study of Kane et al [10]. Similarly, in a retrospective study of nearly 104 patients who underwent diagnostic or therapeutic PCI, those with duration of procedure more than 90 minutes shown a higher risk of CIN development, also shown that use of more than 200 ml of contrast media was associated with further risk for development of CIN [10], and other studies correspond to these findings [30,33,39].
Alcohol use was shown to have significant increase in the risk of CIN; (23.5%) of alcohol users developed CIN. This can be due to the renal tubular dysfunction that results from alcohol consumption which includes: increase urinary excretion of calcium, magnesium, and phosphate; incomplete renal tubular acidosis, and impaired urine-concentrating ability [37]. No other studies found that show a positive correlation between alcohol use and CIN development.

Conclusion
CIN is an important complication that can develop in patients undergoing cardiac catheterization, and it is aggravated by increasing age, presence of DM, HF, IHD, renal impairment, HTN, dyslipidemia, smoking and alcohol use. Also the type of procedure (therapeutic vs. diagnostic), and large volume of contrast agent are important risk factors for CIN development. There was no significant association between gender and development of CIN. So we recommend proper patient selection, appropriate type and low dose of contrast, and adequate hydration by IV normal saline to prevent CIN.