Studying Sex Effect on CTGF, TGF-B1 Levels and Some Relevant Parameters in Iraqi Diabetic Patients with Glomeruli and Renal Tubules Fibrosis:

Reham khuldon Ibrahim; Kadhim  K. Ghudhaib; Ali Abdulmajid Dyab Allawi

doi:10.30526/37.2.3302

Authors

Reham khuldon Ibrahim Department of Chemistry, College of Science for Women, University of Baghdad, Baghdad, Iraq https://orcid.org/0000-0001-8472-3502
Kadhim K. Ghudhaib Department of Medicine College of Medicine, University of Baghdad, Baghdad, Iraq https://orcid.org/0000-0003-4966-4070
Ali Abdulmajid Dyab Allawi Department of Chemistry, College of Science for Women University of Baghdad, Baghdad, Iraq https://orcid.org/0000-0002-1282-1813

DOI:

https://doi.org/10.30526/37.2.3302

Abstract

Due to high blood sugar over long periods, the incidence and prevalence of type 2 diabetes are increasing throughout the world. Diabetic complications include microvascular and macrovascular complications that target the kidneys, nerves, eyes, and heart. Hence, the current study aimed to investigate the levels of (CTGF) and (TGF-β1) for both men and women and to demonstrate the effect of sex on it. In addition, some related biochemical factors in patients with diabetes and diabetic nephropathy are compared with those in healthy controls. The study included 120 males and females with an age range of (30-65) years old. Ninety patients with type 2 diabetes were subdivided into three groups on the basis of ACR criteria. All the individuals in the groups visited Baghdad Teaching Hospital, Medical City, and Al-Yarmouk Teaching Hospital during the period between December 2021 and May 2022. The CTGF and TFG-β1 levels were determined using the ELISA technique. Urea results showed statistically significant differences between diabetic nephropathy in the patient group and the control group in female cases. Still, there were no statistically significant differences between male patients with diabetic nephropathy and the control group. The results also revealed that there were statistically significant differences in ACR, eGFR, urea, FBS, and creatinine between the diabetic nephropathy group and the healthy group for both men and women. From our results, CTGF and TGF-β1 represent good early prognostic markers in diabetic nephropathy.

References

Koska, J.; Gerstein, H.C.; Beisswenger P.J; Reaven, P.D. Advanced glycation end products predict loss of renal function and high-risk chronic kidney disease in type 2 diabetes. Diabetes Care 2022, 45(3),684-691. https://doi.org/10.2337/dc21-2196.

Shao,Y.; Shi, X. Bibliometric analysis and visualization of research progress in the diabetic nephropathy field from 2001 to 2021. Oxidative Medicine and Cellular Longevity 2023, 4555609, 1-16. https://doi.org/10.1155/2023/4555609.

Das, S.; Ramanathan, G. Intestinal microbiome diversity of diabetic and non-diabetic kidney disease: Current status and future perspective. Life Sciences 2023, 316,121414.

https://doi.org/10.1016/j.lfs.2023.121414.

Jiang, S.; Fang, J.; Li, W. Protein restriction for diabetic kidney disease. Cochrane Database of Systematic Reviews 2023, 1(1),CD014906. https://doi.org/10.1002/14651858.CD014906.pub2.

Kučuk, N.; Primozic, M.; Knez Z,; Leitgeb, M.. Sustainable biodegradable biopolymer-based nanoparticles for healthcare applications. International Journal of Molecular Sciences 2023, 24(4), 3188. https://doi.org/10.3390/ijms2404318.

Suzumoto, Y.; Zucaro, L.; Iervolino, A.; Capasso, G. Kidney and blood pressure regulation–latest evidence for molecular mechanisms. Clinical Kidney Journal 2023, 16(6),952-964.

https://doi.org/10.1093/ckj/sfad015.

Linh, H.T.; Iwata,Y.; Senda, Y.; Sakai-Takemori, Y.; Nakade, Y.; Oshima ,M.; Nakagawa-Yoneda, S.; Ogura, H.; Sato, K.; Minami, T.; Kitajima, S. Intestinal bacterial translocation contributes to diabetic kidney disease. Journal of the American Society of Nephrology 2022, 33(6),1105-1119. https://doi: 10.1681/ASN.2021060843.

Fawcett, J.; Scott, J.A. Rapid and precise method for the determination of urea. Journal of Clinical Pathology 1960, 13(2),156-159. https://doi.org/10.1136%2Fjcp.13.2.156.

Ikejezie, J.; Langley, T.; Lewis, S.; Bisanzio, D.; Phalkey, R. The epidemiology of diphtheria in Haiti, December 2014–June 2021: A spatial modeling analysis. PLOS ONE 2022, 17(8),e0273398. https://doi.org/10.1371/journal.pone.0273398.

Pérez-Morales, R.E.; Del Pino, M.D.; Valdivielso, J.M.; Ortiz, A.; Mora-Fernández, C.; Navarro-González, J.F. Inflammation in diabetic kidney disease. Nephron 2019, 143(1),12-16.

https://doi.org/10.1159/000493278.

Fernandez-Fernandez, B.; Fernandez-Prado, R.; Górriz, J.L.; Martinez-Castelao, A.; Navarro-Gonzalez, J.F.; Porrini, E.; Soler, M.J.; Ortiz, A. Canagliflozin and renal events in diabetes with established nephropathy clinical evaluation and study of diabetic nephropathy with atrasentan: what was learned about the treatment of diabetic kidney disease with canagliflozin and atrasentan? Clinical Kidney Journal 2019, 12(3),313-321. https://doi.org/10.1093/ckj/sfz070.

Navaneethan, S.D.; Zoungas, S.; Caramori, M.L.; Chan, J.C.; Heerspink, H.J.; Hurst, C.; Liew, A.; Michos, E.D.; Olowu, W.A.; Sadusky, T.; Tandon, N. Diabetes management in chronic kidney disease: synopsis of the 2020 KDIGO clinical practice guideline. Annals of internal medicine 2021, 174(3),385-94. https://doi.org/10.7326/M20-5938.

Zhuge, Z.; Haworth, S.M.; Nihlén, C.; Carvalho, L.R.; Heuser, S.K.; Kleschyov, A.L.; Nasiell, J.; Cortese-Krott, M.M.; Weitzberg, E.; Lundberg, J.O.; Carlström, M. Red blood cells from endothelial nitric oxide synthase-deficient mice induce vascular dysfunction involving oxidative stress and endothelial arginase I. Redox Biology 2023, 60, 102612. https://doi.org/10.1016/j.redox.2023.102612.

Turner, C.G.; Stanhewicz, A.E.; Nielsen, K.E.; Otis, J.S.; Feresin, R.G.; Wong, B.J. Effects of biological sex and oral contraceptive pill use on cutaneous microvascular endothelial function and nitric oxide-dependent vasodilation in humans. Journal of Applied Physiology 2023, 134(4),858-867. https://doi.org/10.1152/japplphysiol.00586.2022.

Wu, K.C.; Cao, S.;Weaver, C.M.; King, N.J.; Patel, S.; Kim ,T.Y.; Black, D,M.; Kingman, H.; Shafer, M.M.; Rogers, S.J.; Stewart, L. Intestinal calcium absorption decreases after laparoscopic sleeve gastrectomy despite optimization of vitamin D Status. The Journal of Clinical Endocrinology & Metabolism 2023, 108(2),351-360. https://doi.org/10.1210/clinem/dgac579.

Akpoveso, O.O.; Ubah, E.E.; Obasanmi, G. Antioxidant phytochemicals as potential therapy for diabetic complications. Antioxidants 2023, 12(1),123. https://doi.org/10.3390/antiox12010123.

Chaulin, A.M. Gender specificities of cardiac troponin serum levels: From formation mechanisms to the diagnostic role in case of acute coronary syndrome. Life 2023, 13(2),267.

https://doi.org/10.3390/life13020267.

Abd-Elfattah, R.M.; Rashed, L.A; Hassan, F.A. Gene expression of connective tissue growth factor in relation to nephropathy in patients with type 2 diabetes. Azhar International Journal of Pharmaceutical and Medical Sciences 2023, 3(1),172-179.

https://doi.org/10.21608/aijpms.2022.149722.1152.

Sun,Y.; Jin, D.; Zhang, Z.; Zhang, Y.; Zhang, Y.; Kang, X.; Jiang, L.; Tong, X.; Lian, F.. Effects of antioxidants on diabetic kidney diseases: Mechanistic interpretations and clinical assessment. Chinese Medicine 2023, 18(1),1-21. https://doi.org/10.1186/s13020-022-00700-w.

Sutherland, T.E.; Dyer, D.P.; Allen, J.E. The extracellular matrix and the immune system: A mutually dependent relationship. Science 2023, 379(6633),eabp8964. https://doi.org/10.1126/science.abp8964.

Putra, I.M.; Fakhrudin, N.; Nurrochmad, A.; Wahyuono, S.A. Review of medicinal plants with renoprotective activity in diabetic nephropathy animal models. Life 2023, 13(2),560.

https://doi.org/10.3390/life13020560.

Salih, A.A.; Saeedi, S.M.; Ghali, K.H. Impact of fibrosis related to TGF-B1 and TNFR-1 growth factors in renal failure patients. Journal of Medical Research and Health Sciences 2022, 5(7), 2105-2111. https://doi.org/10.52845/JMRHS/2022-5-7-6.

Wei, H.; Li, D.; Luo, Y.; Wang, Y.; Lin, E.; Wei, X. Aluminum exposure induces nephrotoxicity via fibrosis and apoptosis through the TGF-β1/Smads pathway in vivo and in vitro. Ecotoxicology and Environmental Safety 2023, 249,114422. https://doi.org/10.1016/j.ecoenv.2022.114422.

Hirata, R.D.; Genvigir, F.D.; Hirata, T.D.; Cerda, A.; Hirata, M.H. Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes. Brazilian Journal of Pharmaceutical Sciences 2023, 58.

https://doi.org/10.1590/s2175-97902022e201188.

Ke, B.; Shen,W.; Song, J.; Fang, X. MG53: A potential therapeutic target for kidney disease. Pharmacology Research & Perspectives 2023, 11(1),e01049. https://doi.org/10.1002/prp2.1049.

Sinha, R.A. Autophagy: A cellular guardian against hepatic lipotoxicity. Genes 2023, 14(3),553. https://doi.org/10.3390/genes14030553.

Fife, B.T.; Pauken, K.E. The role of the PD‐1 pathway in autoimmunity and peripheral tolerance. Ann N Y Acad Sci 2011, 1217,45-59. https://doi.org/10.1111/j.1749-6632.2010.05919.x.

Lee, Y.H.; Woo, J.H.; Choi, S.J.; Ji, J.D.; Song, G.G.Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus:A meta-analysis. Lupus 2009, 18(1),9-15. https://doi: 10.1177/0961203308093923.

Curran, C.S.; Gupta, S.; Sanz, I.; Sharon, E. PD-1 immunobiology in systemic lupus erythematosus. J Autoimmun 2019, 97(1-9),12. https://doi.org/10.1016/j.jaut.2018.10.025.

Michot, J.M.; Bigenwald, C.; Champiat, S.; Collins, M.; Carbonnel, F.; Postel-Vinay, S.; Berdelou, A.; Varga, A.; Bahleda, R.; Hollebecque, A.; Massard, C. Immune-related adverse events with immune checkpoint blockade:A comprehensive review. Eur J Cancer 2016, 54,139-148.

https://doi.org/10.1016/j.ejca.2015.11.016.