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Study of Serum Neopterin, Interleukin-10 and Neutrophil to Lymphocyte Ratio in Contrast Induced Nephropathy

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Study of Serum Neopterin, Interleukin-10 and Neutrophil to Lymphocyte Ratio in Contrast Induced Nephropathy Z.U.M.J.Vol. 24; No.3 May .;2018 Study of Serum Neopterin, Interleukin-10……. STUDY OF SERUM NEOPTERIN, INTERLEUKIN-10 AND NEUTROPHIL TO LYMPHOCYTE RATIO IN CONTRAST INDUCED NEPHROPATHY Mohamed Aly Fahmy Zanaty MD*, Yousef Ahmed Kadry MD*, Hisham Mohamed Omar MD** and Mohamed Gomaa Abd el-Rehim MSc*. *Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Zagazig University, Egypt. **Clinical Pathology Department, Faculty of Medicine, Zagazig University, Egypt. ABSTRACT Background: Recent improvements in radio-diagnostic procedures and in cardiovascular percutaneous interventions, together with increased life expectancy, have resulted in the subjection of an increasing number of patients to contrast medium-enhanced examinations or cardiac and angiographic procedure requiring iodinated contrast medium injection. Subjects and methods: This study was carried out at Internal Medicine, Cardiology, Radiology and Clinical Pathology departments, Zagazig University Hospitals. The study was approved by Institutional Review Board (IRB) and included a total of 60 patients. Based on the development of contrast induced nephropathy after IV administration of high osmolar contrast agent, Patients were classified into CIN and NO CIN groups. We measured serum neopterin and IL-10 and calculating neutrophil to lymphocyte ratio before contrast administration, 24 and 48 hours after in 45 patients underwent coronary angiography for diagnostic and therapeutic purposes and 15 patients underwent renal angiography. Results: About 25 % of the present studied patients (14 patients) fulfilled the criteria of contrast nephropathy with more cases in the percutaneous coronary angiography group (11 patients).This study revealed that serum neopterin, IL 10 and neutrophil to lymphocyte ratio were higher in patients with CIN following IV contrast media at 24 & 48 hours compared to patients without CIN. In our study; we found increased pre- procedural and post-procedural CRP, ESR and uric acid levels at 48 hours in patients with CIN. We found a decreased basal serum total bilirubin level in patients with CIN following IV contrast media compared to patients without CIN. Conclusion: Serum neopterin, IL 10 and neutrophil to lymphocyte ratio proved that they can be used as early biomarkers of contrast induced nephropathy instead of serum creatinine as they rise 24 hours before any change in the serum creatinine. Decreased serum total bilirubin levels had a higher incidence of CIN after the use of contrast media. Measuring ESR & CRP levels at admission may offer additional assistance in predicting the development of CIN. Elevated serum uric acid level is independently associated with an increased risk of CIN. Abbreviations: CIN = Contrast induced nephropathy, AKI = Acute kidney injury, CRP = C-reactive protein, NLR= Neutrophil to lymphocyte ratio, ESR = Erythrocyte sedimentation rate, UA = Uric acid, eGFR = estimated glomerular filtration rate. Keywords: Contrast induced nephropathy; Neopterin; IL-10; Neutrophil to lymphocyte ratio. Corresponding author: Mohamed Gomaa Abd el-Rehim Mobile: 01064277675 Email: [email protected]. INTRODUCTION induced nephropathy (CIN) has become the cute kidney injury (AKI) represents a third leading cause of hospital-acquired acute A significant and devastating problem in renal failure (2). clinical medicine. The incidence of AKI varies CIN is usually defined as impairment of from 5% of hospitalized patients to 30–50% of renal function occurring within 48 h after patients in intensive care units (1). administration of contrast media and With the increasing use of radio-contrast manifested by an absolute increase in serum media in diagnostic and interventional creatinine concentration of at least 0.5 mg/dl or procedures over the last 30 years, Contrast- Mohamed A., et al….. -239- Z.U.M.J.Vol. 24; No.3 May .;2018 Study of Serum Neopterin, Interleukin-10……. by a relative increase of at least 25% from the artery disease , renal failure , transplant baseline value (3). rejection and diabetes (7). Neutrophil-to-lymphocyte ratio (NLR) Two principal mechanisms have been was introduced as a potential marker to reported for CIN pathogenesis: renal determine inflammation in renal and cardiac vasoconstriction resulting in medullary hypoxia disorders (8). and direct cytotoxic effects of the contrast Interleukin-10 is required for regulating agents. Following the exposure to the contrast immune functions by promoting the wide agent, effects of various mediators (vasopressin spread suppression of immune responses. IL-10 and endothelin) and reduction in the production is effective at decreasing levels of pro- of nitric oxide lead to renal vasoconstriction, inflammatory cytokines that minimizes impaired vasodilation and reduced medullary leukocyte maturation, recruitment and blood flow (4). inflammation (9). Furthermore, tubular injury associated SUBJECTS AND METHODS with oxygen radicals, pro-inflammatory Study design: Cohort study gained the cytokines and complement activity are another approval of Zagazig University Institutional pathophysiologic events that result in tubular Review Board before starting the study. A obstruction in the form of protein precipitates written informed consent was taken from all (5). participants. It was carried out at Cardiology, Experimental studies have shown a Radiology, Internal Medicine and Clinical significant relationship between inflammation Pathology departments, Zagazig University and AKI. First, renal vascular endothelium and Hospitals. tubular epithelium undergo structural and SUBJECTS functional changes due to ischemia, sepsis or This study was applied on 2 groups of patients, nephrotoxic effects. At the next stage, one underwent coronary angiography for inflammatory cells such as macrophages, diagnostic and therapeutic purposes (45 cases) natural killer cells, lymphocytes and and the other underwent renal angiography (15 particularly neutrophils infiltrate damaged cases) using IV (high-osmolar) contrast media tissue leading to further renal destruction in Zagazig university hospitals. Active neutrophils trigger endothelial cellular The patients were classified after IV contrast damage that plays a role in reduced vasodilator adminstration into 2 groups : response, elevated vasoconstrictor response and CIN group : The creatinine level was aggregation of platelets causing physical elevated either by 25% or more of the basal obstruction of capillaries, all of which, in turn level or by ≥ 0.5 mg/dl above the basal level may lead to reduced blood flow, aggravated after 48 hours. ischemic damage and serious destruction in the No CIN group : Rise of the serum creatinine normal tissue (6). level less than 0.5 mg/dl above the basal level Neopterin is a marker of cellular immune after 48 hours. response. Its levels are elevated in several Exclusion criteria : Diabetes mellitus, conditions including autoimmune diseases such Pregnancy and lactation , Presence of known as systemic lupus erythematosus and malignancy , Evidence of current infection , rheumatoid arthritis; infections such as hepatitis inflammation , renal impairment or and human immunodeficiency virus; cancers autoimmune diseases , Nephrotoxic drugs like hepatocellular, gastric and urothelial intake , Patients undergoing dialysis , Patients carcinomas; congestive heart failure, coronary with nephrectomy and Shocked patients or with neurological dysfunction. Mohamed A., et al….. -240- Z.U.M.J.Vol. 24; No.3 May .;2018 Study of Serum Neopterin, Interleukin-10……. All subjects of the study were subjected to the studied groups (I & II) as regard age and sex following: but no statistical significant difference was Full history & full clinical examination. found between studied groups (I & II) as regard Blood samples were withdrawn for BMI. routine investigations (complete urine analysis. Table (2) shows the specific biomarkers data of Fasting & post prandial plasma sugar. studied groups (I &II) before contrast Complete blood picture, serum creatinine and adminstration a statistical significant difference calculation of glomerular filtration rate using was found between studied groups (I & II) as MDRD equation (basal, 24 and 48 hours after regard CIN (number of patients) as 11 subjects contrast administration). Serum uric acid, ESR, of coronary angiography group while only 3 of CRP and Cardiac enzymes (basal and 48 hours renal angiography developed CIN but no after contrast administration). Liver function statistical significant differences were found tests, P.T, PTT and lipid profile. between studied groups (I & II) as regard Blood samples were withdrawn for neopterin , IL 10 , serum creatinine ,eGFR and special investigations (serum neopterin, IL-10 NLR. and calculating neutrophil to lymphocyte ratio Table (3) shows the demographic basal data of (basal, 24 and 48 hours after contrast of patients developed CIN and those without administration). CIN after contrast adminstration , no statistical Aim: To study the interrelation and levels of significant differences were found between neopterin, interleukin-10 and neutrophil to them as regard age , sex and BMI. lymphocyte ratio in contrast induced Table (4) shows the routine laboratory basal nephropathy. data of patients developed CIN and those STATISTICAL ANALYSIS without CIN after adminstration of IV (high- Data were analyzed with SPSS version 20.0 osmolar) contrast , no statistical significant (statistical package for the Social Science). differences were found between studied
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