Role of beta 2 microglobulin in chronic kidney disease

The aim: to study the relationship of beta-2-microglobulin (beta-2 MG) with clinical and laboratory manifestations of chronic kidney disease (CKD).

Patients and Methods. The results of a comprehensive examination of 284 people (118 males and 166 females) aged 18 to 86 years with various types of socially significant diseases were studied. All patients underwent thorough collection of clinical and anamnestic data, laboratory monitoring with the determination of the level of systolic and diastolic blood pressure (BP), body mass index, red blood, beta-2-microglobulin (B2M), lipid profile and proteinuria. Kidney function was assessed according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula using serum creatinine. The main group included 113 patients (55 men and 58 women, mean age 50.9±15.8 years), diagnosed with chronic kidney disease (CKD). The control group consisted of 171 people (63 men and 108 women) with various forms of socially significant diseases, but without signs of CKD. Statistical analysis was carried out using the programs Statistica 10.0 (StatSoft Inc., USA) and Microsoft Office Excel 2010 (Microsoft Corp., USA).

Results. In the subgroup of patients with CKD, signs of renal failure were observed in 46 people in 40.7 % of cases. As CKD progressed, the signs of impaired metabolism of B2M were more severe: its serum level was 8.646 (7.892; 12.231) mg/l at C4 and 18.444 (11.225; 23.717) mg/l at C5 stages of CKD, and urinary excretion was 2.502 (0.305; 6.313) mg/l at C4 and 2.614 (1.535; 25.812) mg/l at C5 stages of CKD. Regardless of renal dysfunction, the median serum B2M level was clinically significantly higher in females (p>0.05). Single-factor one-way correlation analysis showed statistically highly significant relationship was between serum B2M and creatinine levels both in the subgroup of patients with CKD (r = 0.905; p = 0.001) and in the total sample (r = 0.749; p = 0.001). There was a strong negative relationship between serum B2M levels and estimated glomerular filtration rate (GFR) (r = -0.717; p = 0.001). In individuals without CKD, an increase in serum creatinine was closely associated with an increase in urinary excretion of B2M (r=0.252; p=0.005). Simultaneously, in this category of patients, there was a close correlation between estimated GFR with serum B2M level (r= -0.433; p=0.002) and its urinary excretion (r= -0.247; p=0.005). A direct relationship between an increase in serum B2M and an increase in diastolic blood pressure (r=0.274; p=0.034) among CKD patients was established. In the total sample, a direct relationship between the value of systolic BP and serum B2M level (r= 0.223; p=0.01) was registered, as well as between diastolic BP (r= 0.268; p=0.01) and urinary excretion of B2M.

Conclusion. As a result of the study, metabolism of B2M and its relationship with the clinical and laboratory manifestations of CKD were evaluated. The data obtained show high prognostic potential of changes in metabolism of B2M in the population of patients with various forms of socially significant diseases, as well as CKD, which allows to identify among them groups of patients with high and/or very high renal and cardiovascular risk, in order to take timely targeted therapy.

1. Smirnov AV, Dobronravov VA, Kayukov IG. Cardiorenal continuum, pathogenetical grounds of preventive nephrology. Nephrology (Saint-Petersburg) 2005;9(3):7–15. (In Russ.) https://doi.org/10.24884/1561-6274-2005-9-3-7-15

2. Clinical guidelines. Chronic kidney disease (CKD). Nephrology. 2021;25(5):10–82. (In Russ.) doi: 10.36485/1561-6274-2021-25-5-10-82

3. Shilov EM, Yesayan AM, Shilova MM, Kotenko ON. Possible structure of stages of chronic kidney disease in the Russian Federation. Clinical Nephrology 2021;4:6–7.https://dx.doi.org/10.18565/nephrology.2021.4.6-7 (In Russ.)

4. Tomilina ON, Andrusev AM, Peregudova NG, Shinkarev MB. Renal replacement therapy for ESRD in Russian Rederation, 2010–2015. Report of the Russian Renal Replacement Therapy Registry. Part 1. Nephrology and dialysis 2017; app. to T. 19(4):1–95 (In Russ.). https://doi.org/10.28996/1680-4422-2017-4suppl-1-95

5. Levey AS, Coresh J, Bolton K et al. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 Suppl. 1):1–266

6. Williams B, Mancia G, Spiering W et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 2018;36(10):1953–2041

7. Mukhin NA, Tareeva IE, Shilov EM et al. Diagnosis and treatment of kidney diseases. Guide for doctors. «GEOTAR-Media», M., 2008:54–57. (In Russ.)

8. Bogdanova EO, Galkina OV, Zubina IM, Dobronravov VA. Urine proteins and fibrotic lesions of renal compartments in immune glomerulopathies. Nephrology (Saint-Petersburg) 2017;21(6):54–59 (In Russ.) https://doi.org/10.24884/1561-6274-2017-21-6-54-59

9. Güssow D, Rein R, Ginjaar I et al. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. The journal of immunology 1987;139:9:3132–3138

10. Rosenbaum RW, Mayor GH. Beta-2-microglobulin: Metabolism and clinical usefulness. The International Journal of Artificial Organs1981;4:5:215–216

11. Li L, Dong M, Wang XG. The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator. Chin Med J (Engl) 2016;129(4):448–455

12. Gluhovschi C, Gluhovschi G, Christos C et al. Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases. Frontiers in Medicine 2017;4(73): https://doi.org/doi.org/10.3389/fmed.2017.000

13. Bokhanova EG, Dudareva LA, Yankovskaya GV et al. The beta 2-miсroglobulinuriya in the diagnostics chronical tubulo–interstitial nephrytis induced by reception of nonsteroid anti-inflammatory drugs. Journal of Fundamental Medicine and Biology 2014;1:17–20. (In Russ.)

14. Weise M, Prüfer D, Jaques G et al. Beta 2-microglobulin and other proteins as parameter for tubular function. Contributions to nephrology1981;24:88–98

15. Deegens J, Wetzels J. Fractional excretion of high- and lowmolecular weight proteins and outcome in primary focal segmental glomerulosclerosis. Clin Nephrol 2007;68:4:201–208

16. Karlsson FA, Wibell L, Evrin PE. beta 2-Microglobulin in clinical medicine. Scandinavian journal of clinical and laboratory investigation. Supplementum 1980;154:27–37

17. Rameev VV, Kozlovskaya LV. Amyloidosis: modern methods of diagnosis and treatment. Effective pharmacotherapy 2012;44:6–15. (In Russ.)

18. Weissinger EM, Wittke S, Kaiser T et al. Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes. KidneyInt 2004;65(6):2426–2434

19. Matsuo N, Yokoyama K, Maruyama, Y et al. Clinical impact of a combined therapy of peritoneal dialysis and hemodialysis. Clinical nephrology 2010;74:3:209–216

20. Levitskaya ES, Batyushin MM, Khripun AA. Analysis of the effect of 2-microglobulinuria on the risk of cerebral stroke in the long-term period after myocardial revascularization in patients with coronary heart disease. Nephrology 2019;23:80–81. (In Russ.)

21. Statsenko ME, Derevyanchenko MV. Renal function, rigidity of magistral arteries and vascular age in patients with arterial hypertension and type 2 diabetes mellitus. Nephrology (Saint-Petersburg) 2019;23(3):42–48. (In Russ.) https://doi.org/10.24884/1561-6274-2019-23-3-42-48

22. Muhin NA, Kozlovskaya LV, Fomin VV et al. Renal damage in patients with arterial hypertension and hyperuricemia: personalised approach to prognosis. Clinical Nephrology 2014;4:16–20. (In Russ.)

23. Filinyuk Pyu, Rumyantcev AS, Pchelin IYu et al. Cardiometabolic profiles in patients with ischemic heart disease, stage 5 chronic kidney disease, and obesity. Translational Medicine 2022;9:S2:143– 143. (In Russ.)

24. Kals J, Zagura M, Serg M et al. β2-microglobulin, a novel biomarker of peripheral arterial disease, independently predicts aortic stiffness in these patients. Scand J Clin Lab Invest 2011 Jul;71(4):257–263

25. Wilson AM, Kimura E, Harada RK et al. β2-Microglobulin as a Biomarker in Peripheral Arterial Disease. Proteomic Profiling and Clinical Studies. Circulation 2007;116:1396–1403

26. Maslennikova NS, Stukalova OV, Bulkina OS et al. Correlation between the concentration of circulating b2-micriglobulin, dynamic contrast mri data and standard instrumental methods in patients with chronic lower limb ischemia. Russian Cardiology Bulletin 2017;2(12):18–24. (In Russ.)

27. Bobkova IN, Gussaova SS, Stavrovskaya EV. Kidney damage in obesity: variants of the course, mechanisms of development. Therapy 2019;5:6:87–93. (In Russ.). doi:10.18565/therapy.2019.6.87-93

28. Podzolkov VI, Bragina AE. Chronic kidney disease as a multidisciplinary problem of contemporary medicine. Terapevticheskii arkhiv 2018;90:6:121–129. (In Russ.) https://doi.org/10.26442/terarkh2018906121-129

29. Rudenko TE, Bobkova IN, Kamyshova ES, Gorelova IA. Role of the mechanisms of replicative cellular senescence in structural and functional changes of the vascular wall in chronic kidney disease. Therapeutic archive 2017;89:6:102–109. (In Russ.) https://doi.org/10.17116/terarkh2017896102-109

30. Rumyantsev ASh, Rafrafi H, Galkina OV. Calcification of the aortic valve in patients on program hemodialysis. Nephrology (Saint-Petersburg) 2018;22(4):90–95. (In Russ.) https://doi.org/10.24884/1561-6274-2018-22-4-90-95

31. Levitskaya ES, Batiushin MM. Kidney Tubules – Scientific and Applied Value. The Russian Archives of Internal Medicine 2022;12(6):405–421. (In Russ.) https://doi.org/10.20514/2226-6704-2022-12-6-405-421

32. Rumyantsev AS, Kucher AG, Khasun MK. Methods for assessing the functional reserve of the kidneys. Nephrology (Saint-Petersburg) 2022;26(4):127–131. (In Russ.) https://doi.org/10.36485/1561-6274-2022-26-4-127-131

33. Murkamilov IT, Aitbaev KA, Murkamilova ZhA et al. Beta-2-microglobulin as a biomarker in chronic kidney disease. The Scientific Heritage 2021;59-2:45–55. (In Russ.)

34. Lavrishcheva YV, Konradi AO, Jakovenko AA, Rumyantsev AS. Biomarkers of acute post-contrast kidney injury in patients undergoing percutaneous coronary interventions. Nephrology (Saint-Petersburg) 2022;26(2):34–45. (In Russ.) https://doi.org/10.36485/1561-6274-2022-26-2-34-45

35. Kuzyarova AS, Gasanov MZ, Batyushin MM, Golubeva OV. Myostatin in protein-energy wasting in patients on hemodialysis. Nephrology (Saint-Petersburg) 2019;23(3):36–41. (In Russ.) https://doi.org/10.24884/1561-6274-2019-23-3-36-41