Evaluation of Ki-67, CD68 and Bcl-2 staining, dialysis and mortality in crescentic glomerulonephritis

  • Hakan Akdam Aydın Adnan Menderes University, Faculty of Medicine, Division of Nephrology, Aydın, Turkey
  • Mustafa Zeybek Manavgat State Hospital, Department of Internal Medicine, Antalya, Turkey
  • İbrahim Meteoğlu Aydın Adnan Menderes University, Faculty of Medicine Department of Pathology, Aydın, Turkey
  • Yavuz Yeniçerioğlu Aydın Adnan Menderes University, Faculty of Medicine Department of Pathology, Aydın, Turkey
Keywords: crescentic glomerulonephritis, hemodialysis, dialysis, mortality, Ki-67

Abstract

Introduction: Immunohistochemical staining of Ki-67, CD68 and Bcl-2 have been studied in glomerulonephritis. We aimed to assess these immunohistochemical staining features, hemodialysis initiation and 60-month mortality rates in crescentic glomerulonephritis. Methods: In this retrospective study, patients, with a previous diagnosis of crescentic glomerulonephritis were divided into two groups: Hemodialysis Initiated and Not Initiated groups. Kidney biopsy specimens’Ki-67, CD68 and Bcl-2 staining scores were defined as below 5% "0", 5-10% "+1", 11-20% "+2", over 20% "+3". Patients demographic, laboratory data, status of hemodialysis initiation, and mortality were obtained from medical records and immunohistochemical staining scores were compared between groups. Estimated glomerular filtration rates (eGFR) were assessed at 0, 6, and 12 months, except patients’ ongoing hemodialysis. Results: A total of 56 patients were diagnosed as crescentic glomerulonephritis. Pauci-immune crescentic glomerulonephritis (58.9%) was the most common etiology. Hemodialysis was initiated in 36 patients. Mean age, baseline creatinine, urea, C-reactive protein levels were significantly higher and, hemoglobin and proteinuria levels were significantly lower in the Hemodialysis Initiated group. Immunohistochemical staining scores were not significantly different between groups. In Hemodialysis Initiated group, 8.33% of patients were recovered from hemodialysis. Mortality rates were 44,4% and 10% in patients in the group of hemodialysis initiated and not initiated group respectively. When we combine the hemodialysis not initiated patients and patients recovered from hemodialysis; median eGFR at baseline, 6th and 12th month were 32.9, 43.9, and 58.0 mL/min/1.73m2, respectively (p=0.016). Conclusion: Hemodialysis initiation was associated with high mortality. Degree of immunohistochemical staining was similar in both groups. Increment in eGFR was documented in first year in patients, other than the ones on still on hemodialysis.

References

1) Moroni G, Ponticelli C. Rapidly progressive crescentic glomerulonephritis: early treatment is a must. Autoimmun Rev. 2014;13(7):723-9. doi: 10.1016/j.autrev.2014.02.007.

2) Jennette JC. Rapidly progressive crescentic glomerulonephritis. Kidney Int. 2003;63(3):1164-77. doi: 10.1046/j.1523-1755.2003.00843.x.

3) Couser WG. Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis. 1988;11(6):449-64. doi: 10.1016/s0272-6386(88)80079-9.

4) Bullwinkel J, Baron-Lühr B, Lüdemann A, Wohlenberg C, Gerdes J, Scholzen T. Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. J Cell Physiol. 2006;206(3):624-35. doi: 10.1002/jcp.20494.

5) Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182(3):311-22. doi: 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9.

6) Aman NA, Doukoure B, Koffi KD, Koui BS, Traore ZC, Kouyate M, et al. immunohistochemical evaluation of Ki-67 and comparison with clinicopathologic factors in breast carcinomas. Asian Pac J Cancer Prev. 2019;20(1):73-79. doi: 10.31557/APJCP.2019.20.1.73.

7) Zaha DC. Significance of immunohistochemistry in breast cancer. World J Clin Oncol. 2014;5(3):382-92. doi: 10.5306/wjco.v5.i3.382.

8) Tian Y, Ma Z, Chen Z, Li M, Wu Z, Hong M, et al. Clinicopathological and prognostic value of Ki-67 expression in bladder cancer: a systematic review and meta-analysis. PLoS One. 2016;11(7):e0158891. doi: 10.1371/journal.pone.0158891.

9) Chistiakov DA, Killingsworth MC, Myasoedova VA, Orekhov AN, Bobryshev YV. CD68/macrosialin: not just a histochemical marker. Lab Invest. 2017;97(1):4-13. doi: 10.1038/labinvest.2016.116.

10) Dias CB, Malafronte P, Lee J, Resende A, Jorge L, Pinheiro CC, et al. Role of renal expression of CD68 in the long-term prognosis of proliferative lupus nephritis. J Nephrol. 2017;30(1):87-94. doi: 10.1007/s40620-015-0252-7.

11) Zhao L, David MZ, Hyjek E, Chang A, Meehan SM. M2 macrophage infiltrates in the early stages of ANCA-associated pauci-immune necrotizing GN. Clin J Am Soc Nephrol. 2015;10(1):54-62. doi: 10.2215/CJN.03230314.

12) Yang B, Johnson TS, Thomas GL, Watson PF, Wagner B, Furness PN, et al. A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in experimental glomerulonephritis. Kidney Int. 2002;62(4):1301-13. doi: 10.1111/j.1523-1755.2002.kid587.x.

13) Goumenos DS, Tsamandas AC, Kalliakmani P, Tsakas S, Sotsiou F, Bonikos DS, et al. Expression of apoptosis-related proteins bcl-2 and bax along with transforming growth factor (TGF-beta1) in the kidney of patients with glomerulonephritides. Ren Fail. 2004;26(4):361-7. doi: 10.1081/jdi-120039818.

14) Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med.2009;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006.

15) López-Gómez JM, Rivera F; Spanish Registry of Glomerulonephritis. Renal biopsy findings in acute renal failure in the cohort of patients in the Spanish Registry of Glomerulonephritis. Clin J Am Soc Nephrol. 2008;3(3):674-81. doi: 10.2215/CJN.04441007.

16) Koyama A, Yamagata K, Makino H, Arimura Y, Wada T, Nitta K, et al. Japan RPGN Registry Group. A nationwide survey of rapidly progressive glomerulonephritis in Japan: etiology, prognosis and treatment diversity. Clin Exp Nephrol. 2009;13:633-50. doi: 10.1007/s10157-009-0201-7.

17) Jennette JC. Rapidly progressive crescentic glomerulonephritis. Kidney Int. 2003;63(3):1164-77. doi: 10.1046/j.1523-1755.2003.00843.x.

18) Chen S, Tang Z, Xiang H, Li X, Chen H, Zhang H, et al. Etiology and outcome of crescentic glomerulonephritis from a single center in China: a 10-year review. Am J Kidney Dis. 2016;67(3):376-83. doi: 10.1053/j.ajkd.2015.07.034.

19) Rampelli SK, Rajesh NG, Srinivas BH, Harichandra Kumar KT, Swaminathan RP, Priyamvada PS. Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center experience. Indian J Nephrol. 2016;26(4):252-6. doi: 10.4103/0971-4065.158574.

20) Nagaraju SP, Laxminarayana SLK, Kosuru S, Parthasarathy R, Attur RP, Rangaswamy D, et al. Clinicopathological characteristics and outcomes of diffuse crescentic glomerulonephritis: a single center experience from Southern India. J Clin Diagn Res. 2017;11(9):OC21-OC24. doi: 10.7860/JCDR/2017/28307.

21) Alexander S, Yusuf S, Rajan G, Elias John E, Roy S, Annamalai VC, et al. Crescentic glomerulonephritis: what's different in South Asia? A single center observational cohort study. Wellcome Open Res. 2020;5:164. doi:10.12688/wellcomeopenres.16071.1.

22) Nabokov A, Waldherr R, Ritz E. Demonstration of the proliferation marker Ki-67 in renal biopsies: correlation to clinical findings. Am J Kidney Dis. 1997;30(1):87-97. doi: 10.1016/s0272-6386(97)90569-2.

23) Nitta K, Horita S, Honda K, Uchida K, Watanabe T, Nihei H, et al. Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis. Virchows Arch. 1999;435(4):422-7. doi: 10.1007/s004280050420.

24) Kim O. Immunohistochemical study of the expression of alpha-smooth muscle actin and the proliferation marker Ki-67 of glomerulonephritis. J Korean Med Sci. 2001;16(4):455-61. doi: 10.3346/jkms.2001.16.4.455.

25) Dalkilic E, Filiz G, Yavuz M, Dilek K, Ersoy A, Yurtkuran M, et al. Ki-67 proliferation index in renal biopsy samples of patients with systemic lupus erythematosus and its correlation with clinical findings. Iran J Kidney Dis. 2013;7(3):198-203.

26) Rahbar MH, Rahbar MR, Mardanpour N, Mardanpour S. The potential diagnostic utility of coexpression of Ki-67 and P53 in the renal biopsy in pediatric lupus nephritis. Int J Nephrol Renovasc Dis. 2018;11:343-50. doi: 10.2147/IJNRD.S175481.

27) Maekawa K, Shibano T, Sawaki J, Mae H, Hattori M, Tanizawa T. [Clinical usefulness of CD68 staining in children with various glomerular diseases]. Nihon Jinzo Gakkai Shi. 2014;56(4):532-7.

28) Liu ZH, Chen SF, Zhou H, Chen HP, Li LS. Glomerular expression of C-C chemokines in different types of human crescentic glomerulonephritis. Nephrol Dial Transplant. 2003;18(8):1526-34. doi: 10.1093/ndt/gfg172.

29) Nakopoulou L, Stefananki K, Papadakis J, Boletis J, Zeis PM, Kostakis A, et al. Expression of bcl-2 oncoprotein in various types of glomerulonephritis and renal allografts. Nephrol Dial Transplant. 1996;11(6):997-1002.

30) Ko K, Wang J, Perper S, Jiang Y, Yanez D, Kaverina N, et al. Bcl-2 as a therapeutic target in human tubulointerstitial inflammation. Arthritis Rheumatol. 2016;68(11):2740-51. doi: 10.1002/art.39744.

31) Qiu LQ, Sinniah R, I-Hong Hsu S. Downregulation of Bcl-2 by podocytes is associated with progressive glomerular injury and clinical indices of poor renal prognosis in human IgA nephropathy. J Am Soc Nephrol. 2004;15(1):79-90. doi: 10.1097/01.asn.0000104573.54132.2e.

32) Li J, Li H, Li Q, Xue Y. Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression. Turk J Med Sci. 2018;48(4):880-5. doi: 10.3906/sag-1707-44.
Published
2022-03-16
How to Cite
1.
Akdam H, Zeybek M, Meteoğlu İbrahim, Yeniçerioğlu Y. Evaluation of Ki-67, CD68 and Bcl-2 staining, dialysis and mortality in crescentic glomerulonephritis. Rev Nefrol Dial Traspl. [Internet]. 2022Mar.16 [cited 2024Sep.1];42(1):56-4. Available from: http://revistarenal.org.ar/index.php/rndt/article/view/757
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