Stesura Seveso Archivio Italiano di Urologia e Andrologia 2023; 95(4):11869 1 ORIGINAL PAPER INTRODUCTION Malnutrition is one of the most troublesome comorbidi- ties among hemodialysis patients (HD) (1). Factors responsible for malnutrition in HD patients include dial- ysis factors (e.g. low dialysis adequacy, low quality dialy- sis membranes and techniques) and dietary factors (e.g. poor appetite and low diet quality) (2). Poor nutritional status in HD patients was linked to cognitive impairment (3), cardiac dysfunction (4), hospitalization and mortali- ty (5). Assessment of the nutritional status in HD patients is of paramount importance for the sake of better quality of life and clinical outcomes. However, there is a lack of consensus regarding the gold standard indicators (6). Fortunately, our understanding of the pathological mech- anisms involved in malnutrition and muscle wasting in HD patients has markedly improved over years. One of the significant achievements in this context is identifica- tion of myostatin (MSTN)/activin system and its transcrip- tional system (7). MSTN, also known as growth develop- ment factor-8 (GDF-8) was discovered in 1997. It belongs to the transforming growth factor-ß superfamily. The present study aimed to assess MSTN levels in HD patients and its relation to various clinical and biochemi- cal parameters. PATIENTS AND METHODS The present case control study was conducted at Al-Azhar University Hospitals, Cairo, Egypt. The Research Ethics Committee of the Faculty of Medicine, Al-Azhar University (FMG-IRB). approved the study protocol and written informed con- sent was obtained from all participants before enrollment in line with Helsinki Declaration. The study included 60 HD patients who were undergoing hemodialysis for at least rhree years through mature arteri- ovenous fistula that was fashioned by vascular team in vas- Background and aim: Malnutrition is one of the most troublesome comorbidities among hemodialysis patients (HD). Myostatin (MSTN) belongs to the transforming growth factor-β superfamily. In HD patients, MSTN effects are not limited to skeletal muscle growth. The present study aimed to assess MSTN levels in HD patients and its relation to various clinical and biochemical parameters. Patients and methods: The present case control study included 60 patients on HD for at least three years. In addition, there were age and sex-matched healthy subjects who constitutes the control group. Nutritional status was evaluated using the malnu- trition inflammation score (MIS). Muscle wasting in the present study was evaluated using the lean tissue index (LTI) as assessed by the body composition monitor (BCM). Rectus Femoris Muscle (RFM) thickness was also measured as indicator for nutritional status of patient. Results: The present study included 60 HD patients, and age- and sex-matched healthy controls. Patients expressed signifi- cantly higher myostatin levels when compared to controls [medi- an (IQR): 221.3 (153.5-688.2) versus 144.8 (97.0-281.7), p < 0.001]. According to MIS, patients were classified into those with no/mild malnutrition (n = 22) and others with moderate/severe malnutrition (n = 38). Comparison between the two subgroups revealed that the former group had significantly lower myostatin levels [167.7 (150.3-236.3) versus 341.7 (160.9-955.9), p = 0.004]. According to LTI, patients were clas- sified into those with muscle wasting (n = 23) and others with- out muscle wasting (n = 37). Comparative analysis showed that patients in the former group had significantly higher myostatin levels [775.1 (325.1-2133.7) versus 161.8 (142.6-302.3), p < 0.001]. Conclusions: Myostatin seems to be a promising marker for identification of malnutrition and muscle wasting in HD patients. KEY WORDS: Hemodialysis; Malnutrition; Muscle wasting; Myostatin. Submitted 23 September 2023; Accepted 13 November 2023 Relation between myostatin levels and malnutrition and muscle wasting in hemodialysis patients Amal H. Ibrahim 1, Sammar A. Kasim 1, Alshimaa A. Ezzat 2, Noha E. Ibrahim 3, Donia A. Hassan 4, Amira Sh. Ibrahim 5, Tamer A. Abouelgreed 6, Ehab M. Abdo 7, Naglaa M. Aboelsoud 2, Nermeen M. Abdelmonem 8, Mohammad Thabet Alnajem 9, Ahmed A. Aboomar 10 1 Department of Internal Medicine, Nephrology Unit, Al-Azhar University, Cairo, Egypt; 2 Department of Radiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 3 Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre (NRC), Giza, Egypt; 4 Department of Clinical Pathology, Al-Azhar University, Cairo, Egypt; 5 Department of Rheumatology and Rehabilitation, Faculty of Medicine for girls, Al-Azhar University, Cairo, Egypt; 6 Department of Urology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 7 Department of Vascular Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 8 Department of Radiology, Thumbay University Hospital, Ajman, UAE; 9 Department of Radiology, Tawam Hospital, Alain, UAE; 10 Department of internal medicine, Nephrology Unit, Faculty Medicine, Tanta University, Tanta, Egypt. DOI: 10.4081/aiua.2023.11869 Summary Archivio Italiano di Urologia e Andrologia 2023; 95(4):11869 A.H. Ibrahim, S.A. Kasim, A.A. Ezzat, et al. 2 cular department. Patients were excluded if they had other neurological, gastrointestinal or endocrinal conditions with direct effect on the nutritional status or if they have associ- ated malignant tumors. A Control group was selected from hospital staff. They were age and sex-matched healthy sub- jects who constitutes the control group. All participants were submitted to sophisticated history taking, thorough clinical assessment and examination of arterio-venous fistu- la (AVF) and standard laboratory investigations. All partic- ipants were subjected to Ultrasound measurement of rec- tus femoris muscle thickness by a high frequency linear transducer (L12-4 Linear Active Probe) connected to an ultrasound machine (Philips Affinity 30, by: Singha’s medical system India private limited, New Delhi). The ultrasound probe was placed perpendicular to the long axis of the thigh on its anterior surface. The obtained B-mode cross sectional image was adjusted to visualize the rectus femoris muscle, the subcutaneous tissues and the femur. After identifying the muscle tissue, the maximum muscle thick- ness of the rectus femoris muscle was obtained by scanning the muscle through its length until its insertion into the patella. Nutritional status was evaluated using the malnu- trition inflammation score (MIS) (8). Recent studies proved that MIS assessment in HD patients is well correlated with biochemical parameters (9) and showed better perform- ance (10) and prognostic value (11). Patients were divided into two groups according to their MIS values as mild (MIS < 6) and moderate/severe malnu- trition (MIS ≥ 6). Muscle wasting in the present study was evaluated using the lean tissue index (LTI) as assessed by the body composition monitor (BCM). LTI was considered a reli- able indicator of skeletal muscle mass (12). In HD patients, low LTI was related to poor prognosis (13). Patients with LTI < 10.0% of the normal reference range were considered to have muscle wasting (14). Kt/v was calculated by dialy- sis machine, and we take the results from the machines screen. Control patients had controls had only measurement of myostatin. Statistical analysis Data obtained from the present study were presented as number and percent, mean and standard deviation (SD) or median and interquartile range (IQR). Numerical variables were compared using t test or Mann-Whitney U t test, as appropriate while categorical variables were compared using chi-square test. Spearman’s correlation coefficient was used to correlate numerical variables. Binary logistic regression analysis was used to identify predictors of the study outcomes. All statistical procedures were accom- plished using SPSS (Version 27, IBM Corporation, IL, USA). RESULTS The present study included 60 HD patients and age- and sex-matched healthy controls. Patients expressed signifi- Table 1. Association between PPLA score and risk factors for kidney stones or stone recurrence. Malnutrition All patients No/mild Moderate/severe p value n = 60 n = 22 n = 38 Age (years) mean ± SD 54.0 ± 7.9 49.5 ± 6.9 56.5 ± 7.4 0.001 Male/female n 29/31 13/9 16/22 0.21 BMI 24.4 ± 3.4 24.6 ± 2.9 24.3 ± 3.7 0.056 Comorbidities n (%) DM 23 (38.3) 9 (40.9) 14 (36.8) 0.76 HTN 31 (51.7) 13 (59.1) 18 (47.4) 0.38 IHD 17 (28.3) 7 (31.8) 10 (26.3) 0.65 COPD 11 (18.3) 4 (18.2) 7 (18.4) 0.98 HCV 9 (15.0) 3 (13.6) 6 (15.8) 0.82 HD duration (months) 47.0 (28.0-76.0) 45.5 (28.8-67.5) 49.5 (21.0-79.8) 0.84 Kt/V 1.3 ± 0.1 1.4 ± 0.1 1.3 ± 0.1 0.003 Laboratory findings mean ± SD/median (IQR) Hb (gm/dL) 9.8 ± 1.3 10.4 ± 0.3 9.5 ± 1.6 < 0.001 WBCs 5.4 ± 2.0 4.7 ± 1.8 5.9 ± 2.0 0.009 Platelets 188.0 ± 61.9 167.1 ± 63.1 200.3 ± 58.6 0.015 Creatinine (mg/dL) 8.2 ± 2.4 7.9 ± 2.0 8.4 ± 2.6 0.4 Urea (mg/dL) 110.0 ± 32.3 97.6 ± 30.1 117.1 ± 31.7 0.047 FBS (mg/dL) 119.6 ± 46.0 117.2 ± 44.2 120.9 ± 47.5 0.54 Albumin (gm/dL) 4.0 ± 0.4 4.2 ± 0.2 3.8 ± 0.4 < 0.001 Cholesterol (mg/dL) 158.4 ± 44.0 146.3 ± 34.6 165.5 ± 47.6 0.13 Triglycerides (mg/dL) 172.3 ± 114.5 131.8 ± 42.7 195.7 ± 135.4 0.026 Calcium (mg/dL) 8.9 ± 0.8 8.7 ± 0.8 8.9 ± 0.8 0.41 Phosphorus (mg/dL) 4.5 ± 1.5 4.2 ± 1.5 4.6 ± 1.4 0.51 Sodium 138.9 ± 4.8 140.1 ± 5.4 138.1 ± 4.3 0.017 Potassium 4.9 ± 0.6 4.8 ± 0.6 5.0 ± 0.6 0.033 PTH (pg/mL) 407.5 (191.8-895.0) 512.5 (233.0-897.8) 407.5 (187.0-897.8) 0.78 Uric acid (mg/dL) 5.8 ± 1.4 5.6 ± 1.7 5.9 ± 1.3 0.56 Ferritin (ng/mL) 829.4 (752.4-1689.0) 789.0 (370.8-1689.0) 1408.5 (752.4-1726.3) 0.21 hsCRP (mg/L) 111.2 (88.2-121.5) 89.5 (68.6-111.5) 113.9 (100.9-124.0) < 0.001 Myostatin 221.3 (153.5-688.2) 167.7 (150.3-236.3) 341.7 (160.9-955.9) 0.004 Archivio Italiano di Urologia e Andrologia 2023; 95(4):11869 3 Myostatin in hemodialysis cantly higher myostatin levels when compared to controls [median (IQR): 221.3 (153.5-688.2) versus 144.8 (97.0-281.7), p < 0.001]. According to MIS, patients were classified into those with no/mild mal- nutrition (n = 22) and others with moderate/severe malnutrition (n = 38). Comparison between both subgroups revealed that subjects in the former group were significantly younger (49.5 ± 6.9 years versus 56.5 ± 7.4, p = 0.001) with higher Kt/V (1.4 ± 0.1 versus 1.3 ± 0.1, p = 0.003), higher hemoglobin levels (10.4 ± 0.3 gm/dl versus 9.5 ± 1.6, p < 0.001), higher albumin levels (4.2 ± 0.2 gm/dl versus 3.8 ± 0.4), lower triglycerides levels (131.8 ± 42.7 mg/dL versus 195.7 ± 135.4, p = 0.026), lower hsCRP [89.5 (68.6-111.5) mg/dL versus 113.9 (100.9-124.0), p < 0.001] and lower myostatin levels [167.7 (150.3- 236.3) versus 341.7 (160.9-955.9), p = 0.004] (Table 1). According to LTI, patients were classified into those with muscle wasting (n = 23) and others without muscle wasting (n = 37). Comparative analysis showed that patients in the former group are significantly older (58.3 ± 5.2 years versus 51.2 ± 8.2, p < 0.001) with longer HD duration [71.0 (42.0-101.0) months versus 42.0 (24.0-57.0), p = 0.005], lower Kt/V (1.24 ± 0.12 versus 1.37 ± 0.11, p < 0.001), lower hemoglobin (8.7 ± 0.7 gm/dL ver- sus 10.5 ± 1.2, p < 0.001), lower albumin (3.7 ± 0.4 gm/dL versus 4.2 ± 0.3, p < 0.001), higher choles- terol (177.9 ± 51.6 mg/dL versus 146.3 ± 33.9, p = 0.006) and higher triglycerides (226.9 ± 158.5 mg/dL versus 138.4 ± 55.2, p = 0.016). They also showed significantly lower RFM thickness (0.8 +/_ 0.2 versus 1.4 +/- 0.3 cm p 0.001). and signifi- cantly higher hsCRP [113.6 (109.1-121.9) mg/dL versus 100.6 (71.5-131.5), p < 0.001] and myostatin 775.1 (325.1-2133.7) versus 161.8 (142.6-302.3), p < 0.001] levels (Table 2). Comparison between patients with low (< median) and high (≥ median) myostatin levels identified that patients with high myostatin levels were significantly older (57.6 ± 6.4 years versus 50.3 ± 7.8, p < 0.001) with lower albu- min levels (3.8 ± 0.4 versus 4.1 ± 0.3 gm/dL, p = 0.003) and higher hsCRP levels [113.7 (101.8- 122.6) mg/dL versus 101.3 (72.0-116.2), p = 0.005] (Table 3). Correlation analysis recognized significant Table 2. Comparison between hemodialysis patients with and without muscle wasting regarding clinical and laboratory findings. +ve -ve p value n = 23 n = 37 Age (years) mean ± SD 58.3 ± 5.2 51.2 ± 8.2 < 0.001 Male/female n 9/14 20/17 0.26 BMI 23.5 ± 3.5 25.5 ± 0.7 0.12 Comorbidities n (%) DM 12 (52.2) 11 (29.7) 0.082 HTN 13 (56.5) 18 (48.7) 0.55 IHD 7 (30.4) 10 (27.0) 0.78 COPD 5 (21.7) 6 (16.2) 0.59 HCV 4 (17.4) 9 (24.3) 0.53 HD duration (months) 71.0 (42.0-101.0) 42.0 (24.0-57.0) 0.005 Kt/V 1.24 ± 0.12 1.37 ± 0.11 < 0.001 Laboratory findings mean ± SD/median (IQR) Hb (gm/dL) 8.7 ± 0.7 10.5 ± 1.2 < 0.001 WBCs 6.5 ± 1.8 4.8 ± 1.9 < 0.001 Platelets 220.3 ± 46.2 168.1 ± 62.2 < 0.001 Creatinine (mg/dL) 8.0 ± 1.7 8.3 ± 2.8 0.58 Urea (mg/dL) 120.7 ± 30.3 103.3 ± 32.1 0.041 FBS 124.3 ± 51.1 116.6 ± 42.9 0.53 Albumin (gm/dL) 3.7 ± 0.4 4.2 ± 0.3 <0.001 Cholesterol 177.9 ± 51.6 146.3 ± 33.9 0.006 Triglycerides 226.9 ± 158.5 138.4 ± 55.2 0.016 Calcium (mg/dL) 9.0 ± 0.8 8.8 ± 0.9 0.32 Phosphorus (mg/dL) 4.8 ± 1.5 4.3 ± 1.5 0.24 Sodium 137.1 ± 3.6 139.9 ± 5.1 0.026 Potassium 5.1 ± 0.5 4.8 ± 0.6 0.11 PTH (pg/mL) 338.0 (187.0-895.0) 420.0 (262.0-900.5) 0.84 Uric acid (mg/dL) 5.9 ± 0.9 5.7 ± 1.7 0.61 Ferritin (ng/mL) 825.5 (807.0-1603.0) 833.2 (531.6-1689.0) 0.41 hsCRP (mg/L) 113.6 (109.1-121.9) 100.6 (71.5-131.5) < 0.001 Myostatin 775.1 (325.1-2133.7) 161.8 (142.6-302.3) < 0.001 Table 3. Comparison between hemodialysis patients with low and high myostatin levels regarding clinical and laboratory findings. Myostatin levels Low High p value n = 30 n = 30 Age (years) mean ± SD 50.3 ± 7.8 57.6 ± 6.4 < 0.001 Male/female n 12/18 17/13 0.2 BMI 23.9 ± 3.0 25.0 ± 3.8 0.22 Comorbidities n (%) DM 10 (33.3) 13 (43.3) 0.43 HTN 18 (60.0) 13 (43.3) 0.2 IHD 9 (30.0) 8 (26.7) 0.77 COPD 7 (23.3) 4 (13.3) 0.32 HCV 6 (20.0) 3 (10.0) 0.28 HD duration (months) Kt/V 1.34 ± 0.13 1.3 ± 0.14 0.28 Laboratory findings mean ± SD/median (IQR) Hb (gm/dL) 10.1 ± 1.3 9.5 ± 1.3 0.059 WBCs 5.2 ± 2.0 5.7 ± 2.0 0.32 Platelets 182.1 ± 60.5 194.1 ± 63.7 0.46 Creatinine (mg/dL) 8.3 ± 2.1 8.1 ± 2.7 0.87 Urea (mg/dL) 110.1 ± 29.5 109.8 ± 35.4 0.97 FBS 126.8 ± 52.0 112.4 ± 38.5 0.23 Albumin (gm/dL) 4.1 ± 0.3 3.8 ± 0.4 0.003 Cholesterol 155.4 ± 40.2 161.5 ± 47.9 0.59 Triglycerides 137.1 ± 55.2 207.5 ± 145.1 0.018 Calcium (mg/dL) 8.8 ± 0.9 8.9 ± 0.8 0.59 Phosphorus (mg/dL) 4.4 ± 1.5 4.6 ± 1.4 0.51 Sodium 138.7 ± 4.8 139.0 ± 4.8 0.79 Potassium 5.0 ± 0.7 4.9 ± 0.5 0.58 PTH (pg/mL) 311.5 (195.3-897.8) 687.0 (187.0-906.3) 0.32 Uric acid (mg/dL) 5.7 ± 1.4 5.9 ± 1.5 0.66 Ferritin (ng/mL) 1374.0 (370.8-1835.8) 825.5 (752.4-1689.0) 0.75 hsCRP (mg/L) 101.3 (72.0-116.2) 113.7 (101.8-122.6) 0.005 Archivio Italiano di Urologia e Andrologia 2023; 95(4):11869 A.H. Ibrahim, S.A. Kasim, A.A. Ezzat, et al. 4 linear correlation between myostatin levels and age (r = 0.47, p < 0.001), hemoglobin (r = -0.29, p = 0.027) albu- min (r = -0.37, p = 0.004) and hsCRP (r = 0.38, p = 0.003) (Table 4). ROC curve analysis showed good performance of myostatin levels in identification of moderate/severe malnutrition [AUC (95%CI): 0.72 (0.6-0.85)] (Figure 1) and muscle wasting [AUC (95% CI: 0.83 (0.72-0.94)] (Figure 2). DISCUSSION Patients suffering from chronic kidney disease (CKD), mainly those undergoing hemodialysis (HD), often present malnutrition and muscle wasting, which directly correlate with morbidity and mortality (15). In CKD patients, an up-regulation of Myostatin gene expression in skeletal muscle has been found, which was related to IL-6 expression, suggesting a link between MSTN and microinflammation (16). Moreover, it has also been recently described that uremic toxins may accelerate muscle atrophy, by inducing Myostatin expression (17). Myostatin is secreted by the skeletal myocytes into the bloodstream to act back on the secretory cells limiting their proliferation (18). Its actions on the muscular sys- tem are mediated through activation of the ubiquitin-pro- teasome system resulting in inhibition of satellite muscle cell proliferation and differentiation with induction of proteolytic muscle cells (19). In HD patients, MSTN effects are not limited to skeletal muscle growth. They are also linked to insulin resistance, inflammation and cardiovascular morbidity (20). However, studies assessing MSTN in HD patients are scarce and their results are inconsistent, with some stud- ies (21) showing that patients have MSTN levels compa- rable to healthy controls and others reporting higher lev- els of MSTN in the studied patients (22). The present study detected significantly higher myostatin levels in patients under maintenance HD as compared to healthy controls. In addition, we noted higher myostatin expres- sion in HD patients with moderate/severe malnutrition in contrast to their counterparts with no/mild malnutrition. Moreover, those with muscle wasting showed significant- ly higher myostatin levels in contradiction to their peers without muscle wasting. Our conclusions are supported by previous studies. The study of Koyun et al. (23), also noted significantly higher myostatin levels in HD patients as compared to controls. In addition, the study of Delanaye et al. (24), Table 4. Correlation between myostatin levels and clinical and laboratory findings in the studied patients. Myostatin levels r p Age 0.47 <0.001 BMI 0.16 0.22 HD duration -0.03 0.85 Kt/V -0.21 0.11 Hb -0.29 0.027 WBCs 0.17 0.19 Platelets 0.22 0.09 Creatinine 0.13 0.3 Urea 0.08 0.52 FBS -0.22 0.098 Albumin -0.37 0.004 Cholesterol 0.14 0.29 Triglycerides 0.26 0.041 Calcium -0.06 0.66 Phosphorus 0.24 0.031 Sodium -0.07 0.58 Potassium -0.03 0.83 PTH 0.24 0.06 Uric acid 0.18 0.17 Ferritin -0.03 0.84 hsCRP 0.38 0.003 K = clearance of a solute (ml/min). t = time (min. or hr.). v = volume of distribution of a solute (ml or liter). Figure 1. Performance of myostatin levels in identification of moderate/severe malnutrition. Figure 2. Performance of myostatin levels in identification of muscle wasting. Archivio Italiano di Urologia e Andrologia 2023; 95(4):11869 5 Myostatin in hemodialysis reported significant association between muscle mass and myostatin levels. They also noted a significant association between myostatin levels and mortality. The present study also identified a significant correlation between myostatin levels and patients age in accordance with the study of Han et al. (25). Likewise, the study of Yasar et al. (26), on renal transplantation, hemodialysis and peri- toneal dialysis patients showed that myostatin levels were highest in HD patients. Furthermore, they revealed that myostatin was negatively correlated with handgrip strength (HGS, albumin, estimated glomerular filtration rate, and Kt/V. However, myostatin had no correlation with inflammatory markers or appendicular skeletal mus- cle index. Moreover, the study of Bataille et al. (27), found that myostatin together with activin were increased in patients with CKD without increased production attribut- ing this increase to the impaired renal clearance. Similar conclusions were also reported by the study of Widajanti et al. (28), on elderly HD patients. In contrast to our find- ings, the study of Lee et al. (29), concluded that lower myostatin levels were associated with lower muscle mass. In addition, Esposito et al. (21), found no significant dif- ferences between HD patients and healthy controls regarding myostatin levels. They also recognized a posi- tive correlation between myostatin levels and patients’ age and muscle mass. CONCLUSIONS The results of the present study suggest that myostatin may be a promising marker for identification of malnutri- tion and muscle wasting in hemodialysis patients. It shows significant association with poor hemodialysis ade- quacy, anemia and inflammatory marker. REFERENCES 1. Badrasawi M, Zidan S, Sharif I, et al. Prevalence and correlates of malnutrition among hemodialysis patients at hebron governmental hospital, Palestine: cross-sectional study. BMC Nephrol. 2021; 22:214. 2. Sahathevan S, Khor BH, Ng HM, et al. Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review. Nutrients. 2020; 12:3147. 3. 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Association between Sarcopenia and Insulin-Like Growth Factor-1, Myostatin, and Insulin Resistance in Elderly Patients Undergoing Hemodialysis. J Aging Res. 2022; 2022:1327332. 29. Lee SM, Kim SE, Lee JY, et al. Serum myostatin levels are asso- ciated with abdominal aortic calcification in dialysis patients. Kidney Res Clin Pract. 2019; 38:481-489. Correspondence Amal H. Ibrahim, MD mkellany@yahoo.com Department of Internal Medicine, Nephrology Unit, Al-Azhar University, Cairo, Egypt Sammar A. Kasim, MD summerahmed1983@yahoo.com Department of Internal Medicine, Nephrology Unit, Faculty Medicine, Al-Azhar University, Cairo, Egypt Alshimaa A. Ezzat, MD Dr.alshimaa83@gmail.com Department of Radiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Noha E. Ibrahim, MD Nohaelsayed855@gmail.com Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre (NRC), Giza, Egypt Donia A. Hassan, MD dr.donia1@hotmail.com Department of Clinical Pathology, Al-Azhar University, Cairo, Egypt Amira Sh. Ibrahim, MD Amirashahin694@gmail.com Department of Rheumatology and Rehabilitation, Faculty of Medicine for girls, Al-Azhar University, Cairo, Egypt Tamer A. Abouelgreed, MD (Corresponding Author) dr_tamer_ali@yahoo.com tamerali.8@azhar.edu.eg Department of Urology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Ehab M. Abdo, MD ehababdo48@yahoo.com Department of Vascular Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Naglaa M. Aboelsoud, MD nglaa.mahmoud@gmail.com Department of Radiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Nermeen M. Abdelmonem, MD neeermeeenmohamed@gmail.com Department of Radiology, Thumbay University Hospital, Ajman, UAE Mohammad Thabet Alnajem, MD mtnajem@gmail.com Department of Radiology, Tawam Hospital, Alain, UAE. Ahmed A. Aboomar, MD ahmed_abo_omar12@yahoo.com Department of internal medicine, Nephrology Unit, Faculty Medicine, Tanta University, Tanta, Egypt Conflict of interest: The authors declare no potential conflict of interest.