Cardiometabolic Risk Factors and Acute Kidney Injury Based on ...

ORIGINAL ARTICLE

Cardiometabolic Risk Factors and Acute Kidney Injury Based on Urinary Neutrophil Gelatinase Associated Lipocalin (NGALu) in Acute Coronary Syndrome Patients Lazuardhi Dwipa, Rachmat Soelaeman, Rully M.A. Roesli, Erwan Martanto, IGN. Adhiarta Department of Internal Medicine, Padjadjaran University - Hasan Sadikin Hospital. Jl. Pasteur 38 Bandung 40161, Indonesia. Correspondence mail: [email protected], [email protected]

ABSTRAK Tujuan: untuk menganalisis hubungan antara faktor-faktor kardiometabolik dengan gangguan ginjal akut (GgGA) berdasarkan neutrophil gelatinase associated lipocalin urin (NGALu) pada penderita dengan sindroma koroner akut (SKA). Metode: studi potong lintang dilakukan pada pasien dengan SKA yang datang ke Unit Gawat Darurat Rumah Sakit Hasan Sadikin. Sampel urin diperoleh pada saat kedatangan untuk menentukan GgGA secara dini dengan metode ELISA menggunakan NGAL dan dianggap suatu GgGA apabila ≥150 ng/ml. Faktor-faktor kardiometabolik sesuai dengan kriteria MetS oleh IDF tahun 2006. Hasil: terdapat total 60 subjek terdiri dari 39 lakilaki (65%) dan 21 perempuan (35%) usia rata-rata 58,47 (SD 9,9) tahun. Tiga puluh subjek (50%) termasuk GgGA berdasarkan pemeriksaan NGAL urin. Terdapat dua faktor risiko yang berhubungan bermakna dengan GgGA, yaitu tekanan darah (hipertensi) dan HDL (p ≤0,05). HDL merupakan faktor kardiometabolik paling signifikan (p=0,037; OR 5,137 (95% CI 1,102-23,95)). Jumlah faktor yang terdapat pada seseorang juga berhubungan dengan kejadian GgGA, semakin banyak faktor risiko terdapat pada seseorang semakin besar kemungkinan kejadian GgGA (p=0,03). Kesimpulan: faktor tekanan darah dan HDL berhubungan dengan kejadian GgGA pada penderita SKA. Semakin banyak faktor kardiometabolik terdapat pada seorang dengan SKA maka semakin besar kemungkinan kejadian GgGA. Kata kunci: faktor kardiometabolik, sindroma metabolik, sindroma koroner akut, gangguan ginjal akut, NGAL. ABSTRACT Aim: to analyze the association between cardiometabolic risk factors and acute kidney injury (AKI) based on urinary neutrophil gelatinase associated lipocalin (NGALu) in patients with acute coronary syndrome (ACS). Methods: a cross-sectional study was conducted on the ACS patients who were admitted to the Emergency Room in Hasan Sadikin Hospital. Urinary samples were obtained at the time of the arrival and considered AKI if the urinary NGAL level ≥150 ng/ml. The cardiometabolic risk factors were in accord with the IDF criteria for MetS. Results: there were 60 subjects that consisted of 39 men (65%) and 21 women (35%) and the average of was 58.47 (SD 9.9) years. There were 30 subjects (50%) considered AKI based on NGAL level. There were two significant CMR risk factors associated with AKI; blood pressure (hypertension) and HDL (p ≤0.05). HDL being the most significant cardiometabolic factor (p=0.037; OR 5.137 (95% CI 1.102-23.95)). The number of factors was also associated with the incidence of AKI; the more factors existed in a person the greater the incidence of AKI (p=0.03). Conclusion: blood pressure and HDL were cardiometabolic risk factors associated with AKI in ACS patients. The more cardiometabolic factors existed in a person the greater the incidence of AKI. Key words: cardiometabolic risk factors, metabolic syndrome, acute coronary syndrome, acute kidney injury, NGAL.

Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine

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Lazuardhi Dwipa INTRODUCTION

Cardiometabolic Risk (CMR) factors are currently recognized as an early identification of cardiovascular disease and metabolic risk factors. These factors tend to cluster together in one individu and some experts identify it as Cardiometabolic Risk (CMR) while for others is metabolic syndrome (MetS). These factors consist of abdominal/central obesity, insulin resistance (elevated fasting blood glucose or diabetes mellitus type 2), atherogenic dyslipidemia (decreased levels of/HDL cholesterol, elevated levels of triglycerides) and an increased blood pressure.1 The incidence range from 26% to 46% in Acute Coronary Syndrome (ACS) patients and associated with increased morbidity and mortality.1-3 Previous studies showed the incidence of Acute Kidney Injury (AKI) ranged from 10% to 25% in Acute Myocardial Infarction (AMI) patients.4-6 AKI was associated with more than two-fold increased risk of death in hospitals, when severe enough in which kidney replacement is needed if the mortality rate might increase up to 60%.7-8 AKI is also known as an independent risk factor in ACS patients for adverse outcome of the disease and all cause mortality rate in both short and long term. This could happen even in mild increase in creatinine serum and the higher the degree of the impairment of kidney function, the higher the incidence of morbidity and mortality.8-18 Previous studies showed that each cardiometabolic risk factors are also involved in deterioration of kidney function and are independent risk factors for Chronic Kidney Disease (CKD).19 Lately there are several studies that also studied the association between the cluster of cardiometabolic risk factors based on the criteria of MetS with incidence of AKI in patients with Acute Myocardial Infarction (AMI) which indicated that AKI incidence in MetS patients had higher risk than those without MetS. Other studies showed similar result in patients with three vessel diseases undergoing by-pass surgery.20-22 Nonetheless there has not been any study that examines the association between each individual cardiometabolic risk factors based on the MetS criteria with AKI, especially in patients with ACS. This is in fact an important issue for further investigation since there are still differences of opinions among experts about this

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Acta Med Indones-Indones J Intern Med

phenomenon of the clustering cardiometabolic risk factors in one individual whether to classify it as a syndrome or not. Unlike the International Diabetes Foundation (IDF), National Heart, Lung, and Blood Institute (NHLBI) and National Cholesterol Education Program (NCEP), which regard it as a syndrome, the American Diabetes Association (ADA) stated that despite the tendency of cardiometabolic risk factors to be clustered in one individual, one cannot classify it as a syndrome since the basic pathogenesis that may explain each cardiometabolic risk factor as one syndrome is still unclear. Another reason is that currently there has been no single therapy that can address all cardiometabolic risk factors simultaneously but instead the approach is still adressing to each risk factor respectively.1,23 Acute Kidney Injury (AKI) on the other hand, which is based on the AKIN or ADQI criteria have several limitations. The criteria are based on the observation of the increase in creatinine serum and the decrease of urinary output, while in fact, the creatinine serum levels cannot be used in certain conditions such as in acute setting because of the late increase in creatinine serum level (it may take up to two or three days) compared with the actual state of injury that has already occurred in the kidney. Moreover, creatinine serum levels are influenced by various factors of renal and non-renal.5,25 While the observation on urinary output often cannot be used in various clinical conditions such as dehydration, urinary tract obstruction, and the use of diuretics. Meanwhile, especially in ACS patients complicated with acute lung edema setting requires diuretics in its management. Thus, according to the ADQI suggestions a biological marker is needed for the diagnosis of AKI capable of early detecting with a fine sensitivity and specificity.24 Neutrophil Gelatinase Associated Lipocalin (NGAL) is considered as one of the most promising AKI novel biomarkers. Previous studies showed that NGAL is a biological marker which is more a sensitive biological marker AKI compared with other markers.5 In addition, there are other things that can influence the events of AKI in ACS patients. Various kinds of interventions and therapies of ACS such as a primary PCI treatment (Contrast-induced Nephropathy) and drugs (ACE-i, NSAIDs, heparin, furosemide, etc.) may also have a role in the development of AKI. These various therapies may confuse clinicians

Vol 44 • Number 1 • January 2012

whether AKI is caused primarily by ACS or other causes.27-30 NGAL can be a solution to the above mentioned problems because AKI can be detected upon initial arrival in the Emergency Department (ED) before treatment or interventions are given. Therefore, it is necessary to conduct a study to analyze the association of cardiometabolic risk (CMR) factors with the incidence of Acute Kidney Injury, particularly in ACS patients and utilizing a new method with a new biological marker known as NGAL as an alternative method to help recognize AKI in its early stage. METHODS

This is a cross sectional study conducted at the Emergency Department and Cardiac Intensive Care Unit, Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital. The accessible population was those with Acute Coronary Syndrome (ACS) admitted to the Emergency Unit of Hasan Sadikin Hospital (RSHS) Bandung and who were willing to participate in the study. Those with sepsis, history of malignancy, anuria, history of chronic heart failure (CHF), history of chronic kidney disease (CKD) or initial creatinine ≥4 mg/dl were excluded from the study. Data collected included characterics such as sex, age, type of ACS, and the clinical presentation based on Killip classification, prior medications, level of urinary NGAL (NGALu) to determine AKI (NGALu ≥150 ng/ml), history of treatment of hypertension, triglyceride, HDL and diabetes mellitus, as well as data based on the cardiometabolic factors from IDF 2006 which consist of waist circumference, level of blood pressure, fasting blood glucose, HDL, and triglyceride. Sampling was based on the consecutive sampling method until the sample size was reached. Data analysis was done by Chi-square test and multivariate analysis was performed by logistic regression technique to control some identified confounding factors. All data were processed and statistical analyses were done with SPSS 13.0 for Windows. Ethical clearance from the ethical committee for Medical Research in the Faculty of Medicine, University of Padjadjaran was obtained prior to the study, and all subjects signed informed consents.

Cardiometabolic Risk Factors and Acute Kidney Injury RESULTS

Our study recruited a total of 60 subjects to be analyzed. Most are male 39 (65%) while women were 21 subjects (35%). The average of age 58.47 years-old, with the youngest was 32 and the oldest was 78 years old. Most (35%) are in the range of 50-59 year old. The table showed that the majority was STEMI patients; 37 subjects (61.7%) and followed by NSTEMI and UAP, 17 (28.3%) and 6 (10%), respectively. Most of the subjects admitted with the clinical presentation degree of Killip I; 34 subjects (56.7%), followed by the degree of Killip II, IV, and III; 17 men (28.3%), five subjects (8.3%), and four subjects (6.7%), respectively. Research subjects with AKI were 30 subjects (50%). There were more subjects without MetS which were 43 subjects (71.7%) compared to subjects with MetS according to the criteria of the IDF 2006. Incidence of AKI increases according to age (p=0.017), the older the subject, the higher the events. AKI was found significantly more in women 17 subjects (81.0%) than in men whereas in women compared with men (3 subjects (33.3%)) p value