The Role of Urokinase-Type Plasminogen Activator (UPA) Level and Some Biochemical Parameters in Iraqi Hemodialysis Patients

Fatima AL-Sudani; Nawal M.J.  Al-Shammaa

doi:10.30526/37.3.3363

Authors

Fatima AL-Sudani Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq. https://orcid.org/0009-0002-8740-582X
Nawal M.J. Al-Shammaa Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq. https://orcid.org/0000-0002-4062-5035

DOI:

https://doi.org/10.30526/37.3.3363

Keywords:

Urinary-type plasminogen activator, kidney failure, liver enzymes, urea, creatinine, electrolytes.

Abstract

The term end-stage kidney disease (ESKD) is often used to describe people who have the last stage of chronic kidney disease (CKD) and are undergoing dialysis or a kidney transplant for treatment. Hemodialysis (HD) is the most prevalent technique that is utilized to eliminate waste and other hazardous chemicals from the body. The study aims to assess the role of serum Urokinase plasminogen activator (UPA) levels among Iraqi hemodialysis patients. The study encompassed 50 patients aged 40–74 years (21 males and 29 females) admitted to the Iraqi dialysis center at Baghdad Teaching Hospital for the period from October 2022 to February 2023. They were diagnosed based on previous medical reports and laboratory and clinical tests by a consultant nephrologist. UPA, liver enzymes, blood urea, creatinine, albumin, total protein, sodium, potassium, total Ca, and PO₄ levels were determined. This study demonstrates higher levels of UPA in HD patients with ESKD and correlates with ALP; also, UPA can be considered a good marker for the prevention of the development of kidney fibrosis.

References

Humudat, Y. Assessment of the Impact of Anemia on Hematological Parameters among Hemodialysis Patients with Chronic Kidney Disease. Revis Bionatura 2023, 8(1) 32 2018. DOI: https://doi.org/10.21931/RB/2023.08.01.32.

Hashmi, M.F.; Benjamin, O.; Lappin, S.L. End-Stage Renal Disease. StatPearls. Treasure Isl. StatPearls Publ. 2022. PMID: 29763036 Bookshelf ID: NBK499861

Webster, A.C.; Nagler, E. V.; Morton, R.L.; Masson, P. Chronic Kidney Disease. Lancet 2017, 389, 1238–1252.DOI: https://doi.org/10.1016/S0140-6736(16)32064-5

Himmelfarb, J.; Vanholder, R.; Mehrotra, R.; Tonelli, M. The Current and Future Landscape of Dialysis. Nature Reviews Nephrology 2020, 16, 573–585. https://doi.org/10.1038/ s41581-020-0315-4

Ali, A.A.K.J.K.; Abdulmohsin, M.A. The Effect of Some Biochemical and Physiological Parameters in Iraqi Patients with Renal Failure. Parameters 2020, 5, 23–57. DOI: https://doi.org/10.7176/JBAH/10-14-04

Alden, H.M.A.; Abass, E.A.A. Comparative Study of Serum Angiopoietin like Protein-8 and Hyaluronic Acid in Iraqi Hemodialysis Patients with and without T2DM. Annals of the Romanian Society for Cell Biology. 2021, 11085–11094. DOI: https://doi.org/10.13140/RG.2.2.14351.92326.

Mohammad, D.; Karalos, A.; Al-azzawi, R.; Al-Rusafa The Effect of Human Cytomegalovirus on IL-18 Level in Iraqi Kidney Failure Patients. Syst. Rev. Pharm. 2020, 11, 1145–1149. DOI: https://doi.org/10.31838/srp.2020.11.165.

Mehmood, Y.; Ali, I.; Ashraf, U. HEMODIALYSIS;: ACUTE INTRADIALYTIC COMPLICATIONS FOUND ON MAINTENANCE HEMODIALYSIS IN PATIENTS AT A PUBLIC HOSPITAL LAHORE. Prof. Med. J. 2019, 26, 45–50. DOI: https://doi.org/10.29309/TPMJ/2019.26.01.2511

Bowry, S.K.; Kircelli, F.; Misra, M. Flummoxed by Flux: The Indeterminate Principles of Haemodialysis. Clinical Kidney Journal. 2021, 14, i32–i44. https://doi.org/10.1093/ckj/sfab182

Hussin, B.K.; Mohammad, T.U. Correlation Study Between Alanine Aminopeptidase (AAP) And Adiponectin For Patients With Hemodialysis And Other Biochemical Paramrters. J. Educ. Sci. Stud. 2018, 3. DOI:https:/doi.org/10.1093/ckj/sfab182

Disease, E. and causes of chronic kidney; Taal, M.W. Epidemiology and Causes of Chronic Kidney Disease. Medicine (Baltimore). 2019, 47, 562–566. DOI:https://doi.org/10.1016/j.mpmed.2019.06.010

Ng, J.K.; Ma, T.K.; Lai, F.M.; Chow, K.M.; Kwan, B.C.; Leung, C.B.; Li, P.K.; Szeto, C.C. Causes of Nephrotic Syndrome and Nephrotic‐range Proteinuria Are Different in Adult Chinese Patients: A Single Centre Study over 33 Years. Nephrology 2018, 23, 565–572. DOI:https://doi.org/10.1111/nep.13061

Chow, K.M.; Szeto, C.C.; Kwan, B.; Leung, C.B.; Li, P.K. Public Lacks Knowledge on Chronic Kidney Disease: Telephone Survey. Hong Kong Med J 2014, 20, 139–144. DOI: https://doi.org/10.12809/hkmj134134

Buko, A.M.; Kentzer, E.J.; Petros, A.; Menon, G.; Zuiderweg, E.R.; Sarin, V.K. Characterization of a Posttranslational Fucosylation in the Growth Factor Domain of Urinary Plasminogen Activator. Proc. Natl. Acad. Sci. 1991, 88, 3992–3996. DOI: https://doi.org/10.1073/pnas.88.9.399

Gurewich, V. Urokinase and Single-Chain Urokinase-Type Plasminogen Activator (Pro-Urokinase) BT - Fibrinolytics and Antifibrinolytics. In; Bachmann, F., Ed.; Springer Berlin Heidelberg: Berlin, Heidelberg, 2001, 231–260 DOI:https://doi.org/10.1007/978-3-642-56637-0_9

Eddy, A.A.; Fogo, A.B. Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease: Evidence and Mechanisms of Action. Journal of the American Society of Nephrology. 2006, 17, 2999–3012. DOI: https://doi.org/10.1681/ASN.2006050503

Zhang, G. ;Eddy, A. A. (2008). Urokinase and its receptors in chronic kidney disease. Frontiers in bioscience: a journal and virtual library, 13, 5462.Eddy, A.A. Urokinase and Its Receptors in Chronic Kidney Disease. Frontiers in bioscience: a journal and virtual library. 2008, 13, 5462. DOI: https://doi.org/10.2741/3093

Mahmood, N.; Mihalcioiu, C.; Rabbani, S.A. Multifaceted Role of the Urokinase-Type Plasminogen Activator (UPA) and Its Receptor (UPAR): Diagnostic, Prognostic, and Therapeutic Applications. Front. Oncol. 2018, 8, 24. DOI:https://doi.org/10.3389/fonc.2018.00024

Carriero, M.V.; Franco, P.; Vocca, I.; Alfano, D.; Longanesi-Cattani, I.; Bifulco, K.; Mancini, A.; Caputi, M.; Stoppelli, M.P. Structure, Function and Antagonists of Urokinase-Type Plasminogen Activator. Front. Biosci. 2009, 14, 3782–3794. DOI:https://doi.org/10.3389/fonc.2018.00024

Weir, C.B.; Jan, A. BMI Classification Percentile And Cut Off Points; 2019. PMID: 31082114

van der Burgh, A.C.; Rizopoulos, D.; Ikram, M.A.; Hoorn, E.J.; Chaker, L. Determinants of the Evolution of Kidney Function with Age. Kidney international reports 2021, 6, 3054–3063. DOI: https://doi.org/10.1016/j.ekir.2021.10.006

Álvarez-Villarreal, M.; Velarde-García, J.F.; Chocarro-Gonzalez, L.; Pérez-Corrales, J.; Gueita-Rodriguez, J.; Palacios-Ceña, D. Body Changes and Decreased Sexual Drive after Dialysis: A Qualitative Study on the Experiences of Women at an Ambulatory Dialysis Unit in Spain. International journal of environmental research and public health 2019, 16, 3086. DOI::https://doi.org/10.3390/ijerph16173086

Khaleel, F.F.; Hussain, S.S.; Hmood, A.H. Risk Factors of Chronic Kidney Disease among Patients Attending Ibn Sina Teaching Hospital in Mosul City. Iraqi JMS. 2019; 17 (1), 24-31. Doi: 10.22578. IJMS 2019, 17. DOI: https://doi.org/10.22578/IJMS.17.1.5

Zhang, G.; Kernan, K.A.; Thomas, A.; Collins, S.; Song, Y.; Li, L.; Zhu, W.; LeBoeuf, R.C.; Eddy, A.A. A Novel Signaling Pathway: Fibroblast Nicotinic Receptor Α1 Binds Urokinase and Promotes Renal Fibrosis. Journal of Biological Chemistry 2009, 284, 29050–29064. DOI: https://doi.org/10.1074/jbc.M109.010249

Pawlak, K.; Pawlak, D.; Mysliwiec, M. Tissue Factor and Urokinase-Type Plasminogen Activator System Are Related to the Presence of Cardiovascular Disease in Hemodialysis Patients. Thromb. Research. 2007, 120, 871–876. DOI:https://doi.org/10.1016/j.thromres.2007.01.011

Gianella, A.; Nobili, E.; Abbate, M.; Zoja, C.; Gelosa, P.; Mussoni, L.; Bellosta, S.; Canavesi, M.; Rottoli, D.; Guerrini, U. Rosuvastatin Treatment Prevents Progressive Kidney Inflammation and Fibrosis in Stroke-Prone Rats. The American journal of pathology. 2007, 170, 1165–1177. DOI: https://doi.org/10.2353/ajpath.2007.060882

Basta, J.; Robbins, L.; Stout, L.; Prinsen, M.J.; Griggs, D.W.; Rauchman, M. Pharmacologic Inhibition of RGD‐binding Integrins Ameliorates Fibrosis and Improves Function Following Kidney Injury. Physiological reports. 2020, 8, e14329. DOI:https://doi.org/10.14814/phy2.14329

Eddy, A.A. Serine Proteases, Inhibitors and Receptors in Renal Fibrosis. In Proceedings of the Thrombosis and Haemostasis; 2009, 101. DOI: https://doi.org/10.1160/TH08-12-0779

Yamaguchi, I.; Lopez-Guisa, J.M.; Cai, X.; Collins, S.J.; Okamura, D.M.; Eddy, A.A. Endogenous Urokinase Lacks Antifibrotic Activity during Progressive Renal Injury. American Journal of Physiology-Renal Physiology. 2007, 293, F12–F19. DOI:https://doi.org/10.1152/ajprenal.00380.2006

Svenningsen, P.; Hinrichs, G.R.; Zachar, R.; Ydegaard, R.; Jensen, B.L. Physiology and Pathophysiology of the Plasminogen System in the Kidney. Pflügers Archiv-European Journal of Physiology . 2017, 469, 1415–1423. DOI:https://doi.org/10.1007/s00424-017-2014-y

Kovesdy, C.P.; Ureche, V.; Lu, J.L.; Kalantar-Zadeh, K. Outcome Predictability of Serum Alkaline Phosphatase in Men with Pre-Dialysis CKD. Nephrol. Dial. Transplant.2010, 25, 3003–3011. DOI:https://doi.org/10.1093/ndt/gfq144

Sciacqua, A.; Tripepi, G.; Perticone, M.; Cassano, V.; Fiorentino, T. V.; Pititto, G.N.; Maio, R.; Miceli, S.; Andreozzi, F.; Sesti, G.; et al. Alkaline Phosphatase Affects Renal Function in Never-Treated Hypertensive Patients: Effect Modification by Age. Scientific Reports. 2020, 10(1), DOI:: https://doi.org/10.1038/s41598-020-66911-z.

Haarhaus, M.; Cianciolo, G.; Barbuto, S.; La Manna, G.; Gasperoni, L.; Tripepi, G.; Plebani, M.; Fusaro, M.; Magnusson, P. Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease. Nutrients 2022, 14, DOI:: https://doi.org/10.3390/nu14102124.

Sabouri, S.; Aghaee, M.A.; Lotfi, Z.; Esmaily, H.; Alizadeh, M.; Mozafari, H.M. Evaluation of Liver Enzymes in End-Stage Renal Disease Patients on the Renal Transplant-Waiting List in North-West of Iran. Nephro-Urology Monthly. 2020, 12(4). DOI: https://doi.org/10.5812/numonthly.107859

Ray, L.; Nanda, S.K.; Chatterjee, A.; Sarangi, R.; Ganguly, S. A Comparative Study of Serum Aminotransferases in Chronic Kidney Disease with and without End-Stage Renal Disease: Need for New Reference Ranges. International Journal of Applied and Basic Medical Research. 2015, 5, 31. DOI: https://doi.org/10.4103/2229-516X.149232

Ono, K., Ono, T., & Matsumata, T. The Pathogenesis of Decreased Aspartate Aminotransferase and Alanine Aminotransferase Activity in the Plasma of Hemodialysis Patients: The Role of Vitamin B6 Deficiency. Clinical nephrology. 1995, 43, 405–408. PMID: 7554526

Lopes, E.P.; Sette, L.H.B.C.; Sette, J.B.C.; Luna, C.F.; Andrade, A.M.; Moraes, M.; Sette, P.C.A.; Menezes, R.; Cavalcanti, R.L.; Conceição, S.C. Serum Alanine Aminotransferase Levels, Hematocrit Rate and Body Weight Correlations before and after Hemodialysis Session. Clinics 2009, 64, 941–945. DOI:https://doi.org/10.1590/S1807-59322009001000002

Adane, T.; Asrie, F.; Getaneh, Z. Journal of Diabetes, Obesity & Metabolism. 2020. DOI: https://doi.org/10.2147/DMSO.S275392

Murray, I. V; Paolini, M.A. Histology, Kidney and Glomerulus; StatPearls Publishing, Treasure Island (FL), 2023. PMID: 32119431

Alani, M.S.; Al-Mayaly, I.K. Detection of Albumin and Urea in Kidney Failure Patients by Optical Biosensor. Iraqi Journal Science. 2022, 63, 43–52. DOI: https://doi.org/10.24996/ijs.2022.63.1.5

Srivastava, A.; Bodnar, J.; Osman, F.; Jorgenson, M.R.; Astor, B.C.; Mandelbrot, D.A.; Parajuli, S. Serum Albumin Level before Kidney Transplant Predicts Post-Transplant BK and Possibly Cytomegalovirus Infection. Kidney International reports 2020, 5, 2228–2237. DOI:https://doi.org/10.1016/j.ekir.2020.09.012

Jsiem, R.H.; Hasan, H.R.; Husain, M.K. A Biochemical Study for Evaluation and Analysis of Serum Protein of Patients with Different Kidney Tumors. Baghdad Science Journal. 2012, 9, 311–321. DOI: https://doi.org/10.21123/bsj.2012.9.2.311-321

Rhee, C.M.; Ayus, J.C.; Kalantar-Zadeh, K. Hyponatremia in the Dialysis Population. Kidney International reports 2019, 4, 769–780. https://doi.org/10.1016/j.ekir.2019.02.012

Arzhan, S.; Lew, S.Q.; Ing, T.S.; Tzamaloukas, A.H.; Unruh, M.L. Dysnatremias in Chronic Kidney Disease: Pathophysiology, Manifestations, and Treatment. Frontiers in medicine. 2021, 8, 769287. DOI: https://doi.org/10.3389/fmed.2021.769287

Biff, F.P. Regulation of Potassium Homeostasis. Clinical Journal American Society of Nephrology 2015, 10, 1050–1060. DOI: https://doi.org/10.2215/CJN.08580813

Sarnowski, A.; Gama, R.M.; Dawson, A.; Mason, H.; Banerjee, D. Hyperkalemia in Chronic Kidney Disease: Links, Risks and Management. International Journal of Nephrology and Renovascular Disease. 2022, 215–228. DOI: https://doi.org/10.2147/IJNRD.S326464

Kislyy, P.; Parshina, E.; Zulkarnaev, A.; Tolkach, A. MO812: Risk Factors of Long-Term Hypocalcemia After Parathyroidectomy in Dialysis-Dependent Patients. Nephrol. Dial. Transplant. 2022, 37, gfac082-010. DOI: https://doi.org/10.1093/ndt/gfac082.010

Suki, W.N. Renal Transport of Calcium, Magnesium, and Phosphate. Kidney 2000, 520–574. DOI: https://cir.nii.ac.jp/crid/1574231874674402944

O’Neill, W.C. Targeting Serum Calcium in Chronic Kidney Disease and End-Stage Renal Disease: Is Normal Too High? Kidney International. 2016, 89, 40–45. DOI:https://doi.org/10.1016/j.kint.2015.10.001

Anthoni, A.; Supriyadi, R.; Fatimah, S.N. Serum Calcium Levels in Chronic Kidney Disease Patient Stratified by Body Mass Index. Althea Medical Journal. 2019, 6, 55–59. DOI: https://doi.org/10.15850/amj.v6n2.1516