Contrast induced nephropathy (CIN) following percutaneous coronary intervention (PCI) is common with variable incidence [1]. Systematic review and meta-analysis have found that the incidence proportion of CIN after the contrast medium exposure post angiography is 9% and that of acute kidney injury (AKI) requiring renal replacement therapy (RRT) about 0.5% [1]. In majority cases, CIN is preventable with different pharmacological strategies and is generally reversible with long term renal impairment or dialysis events rare [2, 3]. PCI is one of the causes of CIN and predicted risk calculator of CIN after PCI was first described by Mehran et al [4]. National Heart Center, Royal Hospital Oman being a tertiary referral center, there is increasing use of PCI over the last ten years, about 1000- 2000 PCI per annum [5]. Patients and relatives in Oman refuse many a times indicated PCI afraid of CIN which leads to increased coronary related events in these patients. However, there is no data to date about incidence of CIN or their follow up in Oman. Hence, the aim of our study was to assess the incidence, risk factors and short-term outcome (30 days) of CIN in patients in Oman undergoing PCI due to either acute or chronic coronary syndromes. In addition we evaluated the utility of Mehran risk score (MRS) for prediction of CIN in patients undergoing PCI.

A prospective cohort study was carried out at National Heart Center, Royal Hospital, Oman over the period of one year from June, 2020 to May 2021. However, it was interrupted and delayed due to pandemic of COVID-19 infection. The study was approved by the Clinical Research Ethics Committee of Royal Hospital, Muscat, Oman. Ethical approval number: 23547, May 11, 2020.

Inclusion criteria: All consecutive patients over 18 years old with acute or chronic coronary syndrome who underwent PCI were included after taking written informed consent. They were evaluated and followed up by research team up to 30 days. All patients had documented serum creatinine before the procedure, at 48 h after the procedure and at 30 days.

Exclusion criteria: We excluded the patients a) who were under 18 years old, b) who had history of acute kidney injury (AKI)/CIN, c) those were on chronic dialysis, d) were in shock or sepsis during presentation, e) those without data of contrast volume, f) those with staged two procedures during index admission and g) those who refused to give consent. All the elective patients including day care patients were on standard preventive measure of hydration with normal saline at 1 ml/kg/hr. (0.5 ml/kg/hr. if EF < 35%), 4-12 hour before and 6-12 hour after procedure [6,7]. In patients undergoing emergency intervention (primary PCI), intravenous normal saline was administered immediately on arrival in the catheter laboratory and the infusion rate during angioplasty was adjusted to clinical condition/left ventricular ejection fraction (LVEF) by the operator. After the procedure, hydration was continued at 0.5-1 mL/kg of body weight per hour for 6-12 hours accordingly. All the patients were treated with dual antiplatelet therapy and were on high dose statins and those with chronic kidney disease (CKD) were given N-acetylcysteine (NAC) as advised by nephrologists.[3] In patients with CKD, nephrotoxic medications such as metformin, ACE-I/ARB, loop diuretics and NSAIDs were withheld prior to PCI and were resumed 24-48 h after PCI. All patients underwent PCI according to standard protocols with 70% undergoing from radial approach. Low-osmolality contrast media (LOCM) iohexol 350 was used in all patients and the volume documented. Standard procedural precautions in CKD patients like biplane angiography, limiting number of views and contrast injections and using more of fluro saves were employed as per department protocol. Serum creatinine was measured pre-PCI, at 48 hours of PCI and at 30 days from the index procedure which was documented from either clinic visit or from the electronic data system.

We followed the definition of variables as mentioned in the Mehran R et.al [4, 8] and from the Gulf RACE registry [9]. “CIN” was defined as an absolute increase of 44 micro mol/L (0.5 mg/dL) from pre-catheterization serum creatinine at 48 hours after catheterization, or a relative increase of 25% from baseline. ‘‘Anemia’’ was defined using World Health Organization criteria i.e. Hb < 13 gm% in male and < 12 gm% in female. “Chronic kidney disease” was defined as an eGFR of <60 ml/min/1.73 m2 (Levey modified MDRD formula). “Hypotension” was defined as systolic blood pressure <80 mm Hg for at least 1 h requiring inotropic support with medications or intra-aortic balloon pump (IABP) within 24 h per procedurally. Heart failure was defined as New York Heart Association functional classification III/IV and/or history of pulmonary edema. Diabetes was defined as having a history of diabetes diagnosed and/or treated with medication or fasting blood glucose 7.0 mmol/L (126 mg/dL) or greater. Hypertension was defined as having a history of hypertension diagnosed and/or treated with medication, blood pressure greater than 140 mmHg systolic or 90 mmHg diastolic on at least 2 occasions or as receiving any antihypertensive drug. Dyslipidemia was defined as history of dyslipidemia diagnosed and/or treated by a physician or total cholesterol greater than 5.18 mmol/L (200 mg/dL) and/or low-density lipoprotein greater than or equal to 3.37 mmol/L (130 mg/dL). Current smoker was defined as a person smoking cigarettes within 1 month of index admission. MRS was used for predication of CIN [4]. MRS includes following 8 variables and scoring points (in brackets): Hypotension (5), Intra-aortic balloon pump (5), Congestive heart failure class III/IV (5), Age>75 years(4), Anemia(3), Diabetes (3), Contrast media volume (1 for each 100cc),eGFR, mL/min per 1.73m2: 40−60(2), 20−40(4) and <20 (6). Risk 1 or low risk category (≤5 points) is associated with a 7.5% risk of CIN and 0.04% risk of dialysis; risk 2 or moderate risk category (6 to 10 points) with risks of 14% and 0.12%; risk 3 or high risk category (11 to 16 points) with risks of 26.1% and 1.09%; and risk 4 or very high risk category (≥17 points) with risks of 57.3% and 12.6% respectively [4].

Statistical Analysis

The data collection included - demographic, clinical, laboratory, imaging, angiographic data, as well as data relating to management and in-hospital complications. The data was collected prospectively and recorded in the Case Record Form. Statistical analysis was carried out using IBM statistical package for social sciences (SPSS) version 16. Categorical data was reported as absolute values and percentages and continuous data was expressed as mean values ± standard deviation. Comparison between CIN and non-CIN groups of categorical variables (such as age, sex, smoking, hypertension (HTN), diabetes mellitus (DM), dyslipidemia (DLP), anemia, heart failure (HF), diagnosis, emergency procedure, MRS level) were made by using Chi square test whereas student’s t- test was employed for comparison between those groups of continuous variables like laboratory values, contrast volume, LVEF. Univariate and multivariate binary logistic regression analyses was done with risk factors for developing CIN. All observed differences were considered significant if p < 0.05.

Total of 600 patients were screened, 200 patients were enrolled, and 154 patients (77%) were analyzed finally as 46 (23%) patients lost their follow up. Overall, 7.1 %( n=11) patients developed CIN among them 6.3% (n= 9) had only AKI which was improved at 30 day. 1.3% (n=2) patients required in-hospital dialysis. Follow-up was 100% at 30 days. Persistent CIN at 30 days was noted in 1.3% (n=2). There was no mortality. None of the patients required IABP peri-or post procedurally. Table-1 shows the base line characteristics and comparative analysis of total population (n=154), CIN group (n=11) and non-CIN (n=143).

Table1: Baseline characteristics and comparative analysis of risk factors for developing Contrast Induced Nephropathy.

Legend: CIN, Contrast induced nephropathy; LVEF, left ventricular ejection fraction; GFR, glomerular filtration rate; MI, myocardial infarction; STEMI, ST-elevation MI; NSTEMI, non-STE-elevation MI The predominant risk factors for CIN were old age (67.8±11vs 60.6±10), DM (90.9% vs 50.3%), anemia (81.8% vs 29.4 %), HF (81.8% vs 18.2%),) eGFR < 60 ml/min/1.73m2 and increasing MRS of > 11, all with significant p value < 0.05 and they persisted in univariate and multivariate analysis as well (Table 2).

Table2: Univariate and multivariate binary logistic regression analyses of risk factors for developing Contrast Induced Nephropathy.

Legend: CI, confidence interval; GFR, glomerular filtration rate

In addition hypotension was significant risk factor for CIN in univariate analysis. Contrast volume > 100 ml or EF < 50% was not statistically significant for CIN. eGFR level was subdivided into four categories (>60, 40-59, 20-39, <20 ml/min/1.73m2) and as eGFR progressively reduced below 60ml/min/1.73m2 CIN incidence increased to 36.4% (40-59), 27.3% (20-39) and 9.1% (<20) respectively. 90% of patients with eGFR > 60 ml/min/1.73m2 did not develop CIN. With regard to MRS there was underestimation (11-16 score) and overestimation (>17 score) of predicted CIN percentage compared to this study though increasing MRS (>11) lead to increasing CIN incidence in this study (Table 3).

Table3: Comparative analysis of observed and predicted value with Mehran risk score for developing Contrast Induced Nephropathy.

The overall incidence of CIN in this study was less (7.1%) than reported by Mehran et al. (13%) [4], Sgura et al. (14%) [10] and in a recent meta-analysis (9%) [1], but similar to that reported by Abellás-Sequeiros et al. (7.8%) in patients undergoing coronary intervention [11]. In our cohort, the low incidence compared to older studies may be due to the fact that, there was lower proportion of elderly patients (> 75 years), lower prevalence of heart failure (22%) and none required IABP. Baseline CKD is one of strongest independent risk factor for CIN whose prevalence was low in this study population with 86% of patients with eGFR of > 60 mL/min/1.73 m2, which may further explain the low incidence of CIN. In addition, many patients in the study were excluded because they did not have 48-h post procedure creatinine values as most were discharged same day as per policy, missing LVEF data, many did not consent and about 46 patients lost to follow up. Furthermore, incidence of CIN is low probably due to several periprocedural preventive measures already in use at the hospital, including protocolized intravascular volume expansion according to weight, high dose statin use and acetylcysteine/low contrast/biplane angiography in CKD patients, which all can reduce the incidence of CIN [12-14]. In the study from Sgura et al. 14% had CIN in STEMI patients undergoing primary PCI [10]. Our cohort was mixed cases of STEMI (about 24%) and other acute and chronic coronary syndrome patients were in no emergency PCI was done except for those with STEMI which could have led to low incidence of CIN. However in those patients with significant risk factors the incidence was high. In addition, need for RRT during index admission was high (2%) when compared to the meta-analysis (0.5%). The predominant risk factors for CIN were old age, diabetes mellitus, anemia, heart failure, low eGFR and higher Mehran score which are similar to previous reports [1-4, 8, 9, 15]. In this study those who had CIN, 90% were diabetics which indicates that diabetes mellitus is most important in risk factor for CIN. With regard to MRS score, increasing MRS score (>11) led to increasing CIN incidence in this study as noted in previous studies [4, 10, 11]. However, in this study there was underestimation of CIN in the high risk group (11-16 score) and overestimation in the very high risk group (>17 score) of MRS predicted CIN percentage as well as overestimation of MRS for need of dialysis. The predicted percentage of CIN was relatively low in very high score category (>17) than the high scoring group (10-16). Reasons for this discrepancy could be due to very low percentage of our patients in very high risk group (3.2%) when compared to Mehran study cohort who had more patients with contrast volume > 150 ml (80% vs 32%) and use of IABP (7.1% vs 0%) which are predominant reasons for very high risk group and incidence of CIN and need for dialysis. The reason for high incidence of CIN in the high risk group possibly due to periprocedural issues like complex PCI anatomy, no flow or slow flow phenomenon or peri-procedural bleeding for which we did not study and are now being considered in newer MRS which was reported after our study [16]. In addition, over the year’s guideline recommended preventive steps like intravenous normal saline infusion pre and post procedure, high dose statin use and acetylcysteine use along with low contrast with biplane angiography in CKD patients may have prevented CIN in our cohort. Over the last decade, PCI performance has increased dramatically in Oman due to high prevalence of coronary artery disease and acute coronary syndrome[5],[9]. There is a fear among cardiac patients and relatives that PCI causes CIN and many refuse PCI. In this study the low incidence of CIN which was in 98% reversible at 30 days and no need for dialysis at 30 days can reassure patients in making a decision with regard to PCI which is indicated and beneficial especially in CKD patients as coronary events are high in these patients. Therefore, our cardiologists as well as those in Middle East need to use standard scoring method for prediction of CIN after PCI and take guideline recommended precautions in high risk patients in preventing CIN. The Mehran score was published in 2004, but still widely used all over the world as it is simple. Even though as shown in this study higher score may not predict CIN incidence and dialysis as shown in original score, it does show which patients are at risk and in whom precautions can be taken in preventing CIN. Although, there are new scores and methods developed in prediction of CIN after PCI, but their utility in clinical practice is limited as they are either more or less similar to MRS or have a very complex model [17-19] Even though overall CIN incidence was low, need for dialysis in this study is high and in those with risk factors especially diabetes as its prevalence is high in Middle East and Oman, common preventive strategy of hydration with normal saline was found to be inadequate in preventing CIN and renal replacement therapy. Worldwide no consensus reached on exact administration of hydration, duration of administration as well as type of fluid administered. The three common guidelines followed worldwide and also adopted at our institute are: the American College of Radiology guidelines recommend 100 mL/h of intravenous normal saline from 6 to 12 h before angiography until 4 to 12 h following angiography [20], the ESC/EACTS guidelines for myocardial revascularization recommend a regimen of intravenous isotonic saline (1–1.5 mL/kg/h; 0.5ml/kg/h if EF < 35%) from 12 h before until 12 h after the procedure [6] and the KDIGO recommends hydration at a rate of 1 to 1.5 mL/kg/h for 3-4 to 12 h before and 6 to 12 h after procedure with a goal urine volume of > 150 mL/h [7]. Hence there is room for improvement and so in a tertiary institute with high volume PCI it is necessary to take additional novel precautions like the Guard system or hemodynamic guided hydration or contrast reducing or removing systems in preventing CIN specifically in patients with risk factors for CIN as well as consider imaging or physiology guided zero-contrast PCI [21-23].

Limitations

There are some limitations of our study. Firstly, the sample size is low due to recruitment interruption during COVID-19 pandemic, missing data, loss to follow-up as well as many refused to give consent for the study. Therefore, the incidence of CIN may be underestimated. Secondly, it was a single center study, therefore, the general applicability of the results is limited. Finally we did not study the procedural characteristics or complexity of intervention which may have affected the bias of the results.

The overall incidence of CIN in this study was similar to other studies, but was high in those patients with risk factors. In addition, need for renal replacement therapy during index admission was high. The predominant risk factors for CIN were old age, diabetes mellitus, anemia, heart failure and low eGFR. The use of Mehran CIN risk score was able to identify patients with a high likelihood of CIN. Common preventive strategy of hydration with normal saline was found to be inadequate in preventing CIN and renal replacement therapy in high risk group. Hence, in a tertiary institute with high volume PCI it is necessary to take additional novel precautions like the Guard system or hemodynamic guided hydration or contrast reducing or removing systems in preventing CIN specifically in patients with risk factors for CIN as well as consider zero-contrast PCI.

Acknowledgment

We thank all the physicians, nurses from the department of cardiology and Coronary Care Unit of NHC, Muscat, Oman for their help in timely investigations, following the protocols and management of CIN patients.

Funding information

Nil.

Conflicts of interest

There are no conflicts of interest.

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