Indices of connective tissue metabolism, their interconnection in patients with 5D stage chronic kidney disease and in patients with anterior abdominal wall hernias

Objective. To study the interconnection between the indices of matrix metalloproteinases (MMPs) of type I collagen terminal telopeptides in patients with end-stage chronic kidney disease (CKD) and in patients with anterior abdominal wall hearnias.

Materials and methods. 39 patients with CKD stage 5D, 24 patients with primary anterior abdominal wall hernias and 25 patients of the comparison group without visual signs of connective tissue dysplasia were included into the prospective study. The concentrations of the levels of MMP-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-3, N-terminal telopeptide NTX-N, C-terminal telopeptide CTX-C were determined in plasma using the enzyme immunoassay (ELISA).

Results. The end-stage patients with CKD and the patients with anterior abdominal wall hernias showed no statistically signifcant biochemical indices of ongoing bone tissue destruction based on the levels of terminal telopeptides NTX-N and CTX-C. There are statistically signifcant increases in the levels of MMP-1, MMP-2, MMP-9 (p ˂ 0.001) in the CKD stage 5D patients and major TIMP-1 and TIMP-3 (p ˂ 0.001) in relation to the comparison group. These indices were comparable with the changes in the connective tissue of the patients with primary anterior abdominal wall hernias.

Conclusion. The obtained results indicate disturbances in the regulation of the synthesis and structural relationships of connective tissue in CKD stage 5D patients and in patients with primary anterior abdominal wall hernias. CKD stage 5D patients and primary anterior abdominal wall hernias reveal identical direct correlations in the indices of connective tissue metabolism according to NTX-N, MMP-1 and MMP-9, TIMP-1, which indicates similar disturbances in the regulation of the synthesis and structural disorders in connective tissue.

1. Iyer RP, Patterson NL, Fields GB, Lindsey ML. The history of matrix metalloproteinases: milestones, myths, and misperceptions. Am J Physiol Heart Circ Physiol. 2012 Oct 15;303(8):H919-H930. DOI: https://doi.org/10.1152/ajpheart.00577.2012

2. Shadrina AS, Plieva YaZ, Kushlinskiy DN, Morozov AA, Filipenko ML, Chang VL, Kushlinskii NE. Classifcation, regulation of activity, and genetic polymorphism of matrix metalloproteinases in health and disease. Almanac of Clinical Medicine. 2017;45(4):266-279. (In Russ.). DOI: https://doi.org/10.18786/2072-0505-2017-45-4-266-279

3. Markelova EV, Zdor VV, Romanchuk AL, Birko ON. Matrix metalloproteinases: their relationship with the cytokine system, diagnostic and prognostic potential. Immunopathology, Allergology, Infectology. 2016;(2):11-22. (In Russ.). DOI: https://doi.org/10.14427 / jipai.2016.2.11

4. Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev. 2005 Jan;85(1):1-31. DOI: https://doi.org/10.1152/physrev.00048.2003

5. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006 Feb 15;69(3):562-573. DOI: https://doi.org/10.1016/j.cardiores.2005.12.002

6. Zakiyanov O, Kalousová M, Zima T, Tesař V. Matrix Metalloproteinases in Renal Diseases: A Critical Appraisal. Kidney Blood Press Res. 2019;44(3):298-330. DOI: https://doi.org/10.1159/000499876

7. Rogova LN, Shesternina NV, Zamechnik TV, Fastova IA. Matrix metalloproteinases, their role in physiological and pathological processes (review). Bulletin of new medical technologies. 2011;18(2):86-89. (In Russ.)

8. Lesnichenko IF, Gritsaev SV, Kapustin SI. Matrix metalloproteinases: characteristics, role in leukemia and prognostic value. Problems in Oncology. 2011;57(3):286-294. (In Russ.)

9. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003 May 2;92(8):827-839. DOI: https://doi.org/10.1161/01.RES.0000070112.80711.3D

10. Hoegy SE, Oh HR, Corcoran ML, Stetler-Stevenson WG. Tissue inhibitor of metalloproteinases-2 (TIMP-2) suppresses TKR-growth factor signaling independent of metalloproteinase inhibition. J Biol Chem. 2001 Feb 2;276(5):3203-3214. DOI: https://doi.org/10.1074/jbc.M008157200

11. Lovelock JD, Baker AH, Gao F, Dong JF, Bergeron AL, McPheat W, Sivasubramanian N, Mann DL. Heterogeneous effects of tissue inhibitors of matrix metalloproteinases on cardiac fbroblasts. Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H461-H468. DOI: https://doi.org/10.1152/ajpheart.00402.2004

12. Vanhoutte D, Heymans S. TIMPs and cardiac remodeling: ‘Embracing the MMP-independent-side of the family’. J Mol Cell Cardiol. 2010 Mar;48(3):445-453. DOI: https://doi.org/10.1016/j.yjmcc.2009.09.013

13. Parrish AR. Chapter Two - Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target. Prog Mol Biol Transl Sci. 2017;148:31-65. DOI: https://doi.org/10.1016/bs.pmbts.2017.03.001

14. Chetverikov SH, Iashchenko AM, Ier’omin IuV, Vododiuk VIu. Morphological diagnosis of connective tissue dysplasia in patients, suffering postoperative abdominal herni. Klin Khir. 2012 May;(5):19-23. [date of access: 2021 June 11]. Available from: https://repo.odmu.edu.ua/xmlui/handle/123456789/4115 (In Ukr.).

15. Henriksen NA, Yadete DH, Sorensen LT, Agren MS, Jorgensen LN. Connective tissue alteration in abdominal wall hernia. Br J Surg. 2011 Feb;98(2):210-219. DOI: https://doi.org/10.1002/bjs.7339

16. Fedoseev AV, Chekushin AA. Undifferentiated connective tissue dysplasia as one of the mechanisms for the formation of external ventral hernias. Russian medical and biological bulletin named after Academician I.P. Pavlova. 2010;18 (3):125-130. (In Russ.).

17. Smith CT, Katz MG, Foley D, Welch B, Leverson GE, Funk LM, Greenberg JA. Incidence and risk factors of incisional hernia formation following abdominal organ transplantation. Surg Endosc. 2015 Feb;29(2):398-404. DOI: https://doi.org/10.1007/s00464-014-3682-8

18. Varga M, Matia I, Kucera M, Oliverius M, Adamec M. Polypropylene mesh repair of incisional hernia after kidney transplantation: single-center experience and review of the literature. Ann Transplant. 2011 JulSep;16(3):121-125. DOI: https://doi.org/10.12659/aot.882004

19. Petrova AD, Stenina MB, Manzyuk LV, Lyubimova NV, Tyulyandin SA. Time course of changes in bone resorption markers during pamidronate therapy in breast cancer patients with bone metastases. Tumors of female reproductive system. 2013;(1-2):23-27. (In Russ.) DOI: https://doi.org/10.17650/1994-4098-2013-0-1-2-23-27