Diagnostic potential of soluble TNF alpha receptor 1 in diabetic and hypertensive patients with renal impairment and UTI.
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Abstract
Background: Chronic kidney disease is one of the most common diseases. Health care workers in all countries of the world are concerned with the early detection and prevention of kidney diseases. Several novel diagnostic markers are being under investigation nowadays. Tumor necrosis factor-alpha and its receptors are examples.
Aim: The present study was conducted to evaluate the role of tumor necrosis factor α receptor 1 (TNFR1) as a biomarker for detection of renal dysfunction.
Materials and Methods: The study was carried out for the period from February to June 2019 and included 180 patients (their ages were between 19 and 85 years old) and were divided into 60 patients with renal impairment, 60 hemodialysis patients, and 60 patients with normal renal function (as a control group). Each group included patients with hypertension, patients with diabetes mellitus, and hypertensive- diabetic patients.
The patients were attended to Center of Kidney Disease and Transplantation, Dialysis Unit of Baghdad Teaching Hospital – Medical City , Dialysis Unit of Tikrit Teaching Hospital and private laboratory in Samarra City.
Urine sample was collected from each patient for bacteriological study and detection the level of TNFR1.
Results: The most common pathogen isolated from cultured samples was Escherichia coli. Concentration of urinary TNFR1 in hypertensive and or diabetic with normal kidney function compared with hypertensive or and diabetic renal impairment did not differ statistically significant. Conclusion: Urinary level of tumor necrosis factor receptor 1 (TNFR1) is not important in the diagnosis of renal impairment with the presence of hypertension and or diabetes mellitus. Through statistical comparisons of patients with urinary tract infection (UTI) group and those without UTI group , it seems that UTI does not affect the diagnostic ability of urinary TNFR1. We recommend future studies focusing on serum level of the receptors mentioned above to test their diagnostic potential in renal impairment. In addition, investigating the effect of the immunological causes of renal impairment on the level of TNFR, both in urine and serum.
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References
[1] Afkarian, M. et al. (2016). Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014. JAMA, 316(6): 602-610. [2] Ghonemy, T. A., Farag, S. E., Soliman, S. A., El-Okely, A., and El-Hendy, Y. (2016). Epidemiology and risk factors of chronic kidney disease in the El-Sharkia Governorate, Egypt. Saudi Journal of Kidney Diseases and Transplantation, 27(1): 111-112. [3] Vaidya, V. S., Ferguson, M. A., and Bonventre, J. V. (2008). Biomarkers of acute kidney injury. Annu. Rev. Pharmacol. Toxicol., 48(2): 463-493. [4] Di Somma, S., and Marino, R. (2019). Diagnosis and Management of Acute Kidney Injury in the Emergency Department. In Critical Care Nephrology, 2(2):1296-1301. [5] Tangri, N. et al. (2012). Filtration markers may have prognostic value independent of glomerular filtration rate. Journal of the American Society of Nephrology, 23(2): 351-359. [6] Foster, M. C. et al. (2015). Filtration markers as predictors of ESRD and mortality in Southwestern American Indians with type 2 diabetes. American Journal of Kidney Diseases, 66(1): 75-83. [7] Turner, M. E. et al. (2017). Validation of a routine two‐sample iohexol plasma clearance assessment of GFR and an evaluation of common endogenous markers in a rat model of CKD. Physiological reports, 5(9):e13205. [8] Alshamaa, S. D., and Al-Obaidi, S. H. (2018). Detection of some Biochemical Indicators and Auto-Fluorescence Spectrophotometer of Kidney Disease and Renal Failure Patient's Urine. Rafidain Journal of Science, 27(4E): 1-11. [9] Adiyanti, S. S., and Loho, T. (2012). Acute kidney injury (AKI) biomarker. Acta Med Indones, 44(3): 246-55. [10] Chacar, F. et al. (2017). Urinary Tamm‐Horsfall protein, albumin, vitamin D‐binding protein, and retinol‐binding protein as early biomarkers of chronic kidney disease in dogs. Physiological reports, 5(11): e13262. [11] Lobato, G. R., Lobato, M. R., Thome, F. S., and Veronese, F. V. (2017). Performance of urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and N-acetyl-β-D-glucosaminidase to predict chronic kidney disease progression and adverse outcomes. Brazilian Journal of Medical and Biological Research, 50(5):88-90. [12] Urbschat, A., Obermüller, N., and Haferkamp, A. (2011). Biomarkers of kidney injury. Biomarkers, 16 (1): S22-S30. [13] Nakano, C. et al. (2012). Combined use of vitamin D status and FGF23 for risk stratification of renal outcome. Clinical Journal of the American Society of Nephrology, 7(5):810-819. [14] El Dayem, S. A., El magd El Bohy, A., and El Shehaby, A. (2016). Value of the intrarenal arterial resistivity indices and different renal biomarkers for early identification of diabetic nephropathy in type 1 diabetic patients. Journal of Pediatric Endocrinology and Metabolism, 29(3): 273-279. [15] Singbartl, K., Formeck, C. L., and Kellum, J. A. (2019). Kidney-immune system crosstalk in AKI. In: Seminars in Nephrology 39( 1): 96-106. [16] Parameswaran, N., and Patial, S. (2010). Tumor necrosis factor-α signaling in macrophages. Critical Reviews™ in Eukaryotic Gene Expression,20(2):111-112. [17] Ramseyer, V. D., and Garvin, J. L. (2013). Tumor necrosis factor-α: regulation of renal function and blood pressure. American Journal of Physiology-Renal Physiology, 304(10): F1231-F1242. [18] Therrien, F. J., Agharazii, M., Lebel, M., and Larivière, R. (2012). Neutralization of tumor necrosis factor-alpha reduces renal fibrosis and hypertension in rats with renal failure. American journal of nephrology, 36(2): 151-161. [19] Mehaffey, E. P., Castillo, A., Navar, L. G., and Majid, D. S. (2016). Intrarenal angiotensinogen production induced by chronic angiotensin II and high salt intake is augmented in tumor necrosis factor-alpha receptor type 1 knockout mice. The FASEB Journal, 30(1_supplement), 1216-13. [20] Castillo, A., Islam, M. T., Prieto, M. C., and Majid, D. S. (2012). Tumor necrosis factor-α receptor type 1, not type 2, mediates its acute responses in the kidney. American Journal of Physiology-Renal Physiology, 302(12): F1650-F1657. [21] Majid, D. S. (2011). Tumor necrosis factor-α and kidney function: experimental findings in mice.
In: Advances in TNF Family Research. Springer, New York, NY. 471-480 [22] Niewczas, M. A. et al. (2012). Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. Journal of the American Society of Nephrology, 23(3): 507-515. [23] Xun, C., and Zhao, Y. (2017). Potential role of soluble TNF-α receptors in diagnosis of patients with chronic kidney disease. Annals of Clinical & Laboratory Science, 47(3): 310-314. [24] Thass, N., Kumar, M. and Kaur, R., (2019). Prevalence and antibiogram of bacterial pathogens causing urinary tract infection in a tertiary care hospital. International Journal of Medical Science and Public Health, 8(1): 53-58. [25] Vakili, M. et al. (2018). The pattern of antibiotic resistance of pathogens isolated from urine cultures of patients referred to Yazd Central Laboratory in 2012-2013. Biomedical Research and Therapy, 5(5):2271-2278. [26] Odoki, M. et al. (2019). Prevalence of Bacterial Urinary Tract Infections and Associated Factors among Patients Attending Hospitals in Bushenyi District, Uganda. International Journal of Microbiology, 3(1):85-86. [27] Mosser, D. M., and Edwards, J. P. (2008). Exploring the full spectrum of macrophage activation. Nature reviews immunology, 8(12), 958. [28] Belge, K. U. et al. (2002). The proinflammatory CD14+ CD16+ DR++ monocytes are a major source of TNF. The Journal of Immunology, 168(7): 3536-3542. [29] Medzhitov, R. (2007). Recognition of microorganisms and activation of the immune response. Nature, 449(7164), 819. [30] Roulis, M., Armaka, M., Manoloukos, M., Apostolaki, M., and Kollias, G. (2011). Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology. Proceedings of the National Academy of Sciences, 108(13): 5396-5401. [31] Theilgaard - Mönch, K. et al. (2005). The transcriptional program of terminal granulocytic differentiation. Blood, 105(4):1785-1796. [32] Chen, L., Zhang, Z., Barletta, K. E., Burdick, M. D., and Mehrad, B. (2013). Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors. American Journal of Physiology-Lung Cellular and Molecular Physiology, 305(10): L702-L711. [33] Djojodimedjo, T., and Soebadi, D. M. (2013). Escherichia coli infection induces mucosal damage and expression of proteins promoting urinary stone formation. Urolithiasis, 41(4):295-301. [34] Engel, D. et al. (2006). Tumor necrosis factor alpha-and inducible nitric oxide synthase-producing dendritic cells are rapidly recruited to the bladder in urinary tract infection but are dispensable for bacterial clearance. Infection and Immunity, 74(11):6100-6107. [35] Mohkam, M. et al. (2009). Diagnostic potential of urinary tumor necrosis factor-alpha in children with acute pyelonephritis. Iranian Journal of Kidney Diseases, 3(2): 66-67. [36] Davidoff, R., Yamaguchi, R., Leach, G. E., Park, E.,and Lad, P. M. (1997). Multiple urinary cytokine levels of bacterial cystitis. The Journal of Urology, 157(5):1980-1985. [37] Sadeghi, M. et al. (2005). Strong inflammatory cytokine response in male and strong anti inflammatory response in female kidney transplant recipients with urinary tract infection. Transplant International, 18(2):177-185. [38] Olszyna, D. P. et al. (1998). Levels of inhibitors of tumor necrosis factor alpha and interleukin 1β in urine and sera of patients with urosepsis. Infection and immunity, 66(8): 3527-3534. [39] Kim, K. H., Hong, Y. M., and Kim, G. H. (1997). Urinary Interleukin-1β Levels in Children with Urinary Tract Infection. Journal of the Korean Pediatric Society, 40(7):981-990. [40] Puszkarska, A., Niklas, A., Gluszek, J., Lipski, D., and Niklas, K. (2019). The concentration of tumor necrosis factor in the blood serum and in the urine and selected early organ damages in patients with primary systemic arterial hypertension. Medicine, 98(22), e15773. [41] Xun, C., and Zhao, Y. (2017). Potential role of soluble TNF-α receptors in diagnosis of patients with chronic kidney disease. Annals of Clinical & Laboratory Science, 47(3): 310-314. [42] Matura, L. A. et al. (2015). Interleukin-6 and Tumor Necrosis Factor-α Are Associated with Quality of Life–Related Symptoms in Pulmonary Arterial Hypertension. Annals of the American Thoracic Society, 12(3):370-375. [43] Islam, M. N. et al. (2017). Serum and urine soluble tnfr-1 and tnfr-2 differentially correlate with egfr and albuminuria in diabetic kidney disease. Nephrology Dialysis Transplantation, 32(suppl_3), iii10-iii11. [44] Griffin, T. P. et al. (2017). Clinical utility of serum and urine soluble tnfr-1 and tnfr-2 in diabetic kidney disease. Irish Journal of Medical Science 186(5): S367-S367.