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The correlation of interstitial change with renal prognosis in patients with myeloperoxidase-ANCA-associated glomerulonephritis: a single-center retrospective analysis

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Abstract

Objects

We aim to explore the correlation between active/chronic tubulointerstitial injury and renal survival, and to compare their predictive value in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN).

Method

A total of 225 patients with MPO-AAGN diagnosed between February 2004 and December 2020 were included. Survival and univariate/multivariate Cox regression analyses were used to analyze the prognostic value of interstitial inflammation and interstitial fibrosis/tubular atrophy (IF/TA).

Results

Of the 225 patients, 73 (32.4%) patients developed end-stage renal disease (ESRD) requiring maintenance dialysis. Interstitial inflammation>50% and IF/TA>50% were important predictors for ESRD in MPO-AAGN in multivariate Cox regression analysis adjusted by age, gender, estimated glomerular filtration rate (eGFR)≤15 ml/min/1.73m2, and normal glomeruli% (classified by <25%, 25–50%, >50%). Furthermore, we conducted stratified Cox regression analysis and found different results in the subgroups of eGFR>15 ml/min/1.73m2 and eGFR≤15 ml/min/1.73m2. Interstitial inflammation>50% and IF/TA>50% were significant risk factors for ESRD in the subgroup of eGFR>15 ml/min/1.73m2, but not or less significant in the subgroup of eGFR≤15 ml/min/1.73m2. Similarly, the survival analysis according to interstitial inflammation>50%/≤50% and IF/TA>50%/≤50% showed significant differences in the subgroup of eGFR>15 ml/min/1.73m2, but not or less significant in the subgroup of eGFR≤15 ml/min/1.73m2.

Conclusions

Interstitial inflammation>50% and IF/TA>50% were prognostic factors for renal survival in MPO-AAGN. In particular, interstitial inflammation and IF/TA had a better predictive ability in the subgroup of eGFR>15 ml/min/1.73m2.

Key Points

• Interstitial inflammation>50% and IF/TA>50% can help to predict renal survival in MPO-AAGN.

• Both interstitial inflammation and IF/TA had a better predictive ability in the subgroup of eGFR>15 ml/min/1.73m2 than those in the subgroup of eGFR≤15 ml/min/1.73m2.

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References

  1. Akao S, Yamagiwa G, Hazue R, Rokutanda R, Suzuki T (2023) Kidney biopsy in patients with antineutrophil cytoplasmic antibody-associated vasculitis with mild renal abnormality. CEN Case Rep 12(1):50–55. https://doi.org/10.1007/s13730-022-00719-w

    Article  PubMed  Google Scholar 

  2. Chen Z, Lin L, Yang W, Chen N, Lin Y (2020) Clinical characteristics and prognostic risk factors of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Int Immunopharmacol 87:106819. https://doi.org/10.1016/j.intimp.2020.106819

    Article  PubMed  CAS  Google Scholar 

  3. Domínguez-Quintana M, Alba MA, Hinojosa-Azaola A (2021) Classification of ANCA-associated vasculitis: differences based on ANCA specificity and clinicopathologic phenotype. Rheumatol Int 41(10):1717–1728. https://doi.org/10.1007/s00296-021-04966-5

    Article  PubMed  Google Scholar 

  4. Berti A, Cornec-Le Gall E, Cornec D, Casal Moura M, Matteson EL, Crowson CS, Ravindran A, Sethi S, Fervenza FC, Specks U (2019) Incidence, prevalence, mortality and chronic renal damage of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in a 20-year population-based cohort. Nephrol Dial Transplant 34(9):1508–1517. https://doi.org/10.1093/ndt/gfy250

    Article  PubMed  CAS  Google Scholar 

  5. Tampe D, Schridde L, Korsten P, Ströbel P, Zeisberg M, Hakroush S, Tampe B (2021) Different patterns of kidney fibrosis are indicative of injury to distinct renal compartments. Cells 10(8). https://doi.org/10.3390/cells10082014

  6. Saritas T, Kramann R (2021) Kidney allograft fibrosis: diagnostic and therapeutic strategies. Transplantation 105(10):e114–e130. https://doi.org/10.1097/tp.0000000000003678

    Article  PubMed  CAS  Google Scholar 

  7. Hajji M, Barbouch S, Goucha R, Hamida FB, Gorsane I, Abderrahim E (2022) Thirty years of experience with anti-neutrophil cytoplasmic antibody glomerulonephritis in Charles Nicolle Hospital-Tunisia: a retrospective cohort study. Pan Afr Med J 42(84). https://doi.org/10.11604/pamj.2022.42.84.27914

  8. Brix SR, Noriega M, Tennstedt P, Vettorazzi E, Busch M, Nitschke M, Jabs WJ, Özcan F, Wendt R, Hausberg M et al (2018) Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int 94(6):1177–1188. https://doi.org/10.1016/j.kint.2018.07.020

    Article  PubMed  CAS  Google Scholar 

  9. Berden AE, Jones RB, Erasmus DD, Walsh M, Noël LH, Ferrario F, Waldherr R, Bruijn JA, Jayne DR, Bajema IM (2012) Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody-associated glomerulonephritis after rituximab therapy. J Am Soc Nephrol 23(2):313–321. https://doi.org/10.1681/asn.2011040330

    Article  PubMed  CAS  Google Scholar 

  10. Liu Y (2011) Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol 7(12):684–696. https://doi.org/10.1038/nrneph.2011.149

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Brix SR, Noriega M, Herden EM, Goldmann B, Langbehn U, Busch M, Jabs WJ, Steinmetz OM, Panzer U, Huber TB et al (2018) Organisation of lymphocytic infiltrates in ANCA-associated glomerulonephritis. Histopathology 72(7):1093–1101. https://doi.org/10.1111/his.13487

    Article  PubMed  Google Scholar 

  12. Bajema IM, Hagen EC, Hermans J, Noël LH, Waldherr R, Ferrario F, Van Der Woude FJ, Bruijn JA (1999) Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis. Kidney Int 56(5):1751–1758. https://doi.org/10.1046/j.1523-1755.1999.00758.x

    Article  PubMed  CAS  Google Scholar 

  13. Vizjak A, Rott T, Koselj-Kajtna M, Rozman B, Kaplan-Pavlovcic S, Ferluga D (2003) Histologic and immunohistologic study and clinical presentation of ANCA-associated glomerulonephritis with correlation to ANCA antigen specificity. Am J Kidney Dis 41(3):539–549. https://doi.org/10.1053/ajkd.2003.50142

    Article  PubMed  Google Scholar 

  14. Hakroush S, Kluge IA, Ströbel P, Korsten P, Tampe D, Tampe B (2021) Systematic histological scoring reveals more prominent interstitial inflammation in myeloperoxidase-ANCA compared to proteinase 3-ANCA glomerulonephritis. J Clin Med 10(6). https://doi.org/10.3390/jcm10061231

  15. Hakroush S, Tampe D, Ströbel P, Korsten P, Tampe B (2021) Comparative histological subtyping of immune cell infiltrates in MPO-ANCA and PR3-ANCA glomerulonephritis. Front Immunol 12:737708. https://doi.org/10.3389/fimmu.2021.737708

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Booth AD, Almond MK, Burns A, Ellis P, Gaskin G, Neild GH, Plaisance M, Pusey CD, Jayne DR (2003) Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis 41(4):776–784. https://doi.org/10.1016/s0272-6386(03)00025-8

    Article  PubMed  Google Scholar 

  17. Moiseev S, Novikov P, Jayne D, Mukhin N (2017) End-stage renal disease in ANCA-associated vasculitis. Nephrol Dial Transplant 32(2):248–253. https://doi.org/10.1093/ndt/gfw046

    Article  PubMed  CAS  Google Scholar 

  18. Binda V, Moroni G, Messa P (2018) ANCA-associated vasculitis with renal involvement. J Nephrol 31(2):197–208. https://doi.org/10.1007/s40620-017-0412-z

    Article  PubMed  CAS  Google Scholar 

  19. Lionaki S, Hogan SL, Jennette CE, Hu Y, Hamra JB, Jennette JC, Falk RJ, Nachman PH (2009) The clinical course of ANCA small-vessel vasculitis on chronic dialysis. Kidney Int 76(6):644–651. https://doi.org/10.1038/ki.2009.218

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kong W, Ni A, Wang M, Huang X, Chen L, Ma Y, Chen J, Han F (2023) The predictive value of Berden’s classification versus renal risk score for renal survival of Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. Clin Exp Rheumatol 41(4):893–901. https://doi.org/10.55563/clinexprheumatol/ozkrr0

    Article  PubMed  Google Scholar 

  21. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC et al (2013) 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 65(1):1–11. https://doi.org/10.1002/art.37715

    Article  PubMed  CAS  Google Scholar 

  22. Suppiah R, Robson JC, Grayson PC, Ponte C, Craven A, Khalid S, Judge A, Hutchings A, Merkel PA, Luqmani RA et al (2022) 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Arthritis Rheumatol 74(3):400–406. https://doi.org/10.1002/art.41983

    Article  PubMed  CAS  Google Scholar 

  23. Reaves AC, Weiner DE (2021) The ESRD quality incentive program: everything can be improved. Am J Kidney Dis 78(6):907–910. https://doi.org/10.1053/j.ajkd.2021.08.004

    Article  PubMed  Google Scholar 

  24. Vergunst CE, van Gurp E, Hagen EC, van Houwelingen HC, Hauer HA, Noël LH, Waldherr R, Ferrario F, van der Woude FJ, Bruijn JA et al (2003) An index for renal outcome in ANCA-associated glomerulonephritis. Am J Kidney Dis 41(3):532–538. https://doi.org/10.1053/ajkd.2003.50115

    Article  PubMed  Google Scholar 

  25. Haridasan S, Ganesh RN, Parameswaran S, Priyamvada PS (2019) Manifest interstitial and vascular pathology in anti-neutrophil cytoplasmic antibody-associated renal disease. Saudi J Kidney Dis Transpl 30(3):726–734. https://doi.org/10.4103/1319-2442.261359

    Article  PubMed  Google Scholar 

  26. Hauer HA, Bajema IM, Van Houwelingen HC, Ferrario F, Noël LH, Waldherr R, Jayne DR, Rasmussen N, Bruijn JA, Hagen EC (2002) Determinants of outcome in ANCA-associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients. Kidney Int 62(5):1732–1742. https://doi.org/10.1046/j.1523-1755.2002.00605.x

    Article  PubMed  Google Scholar 

  27. Ford SL, Polkinghorne KR, Longano A, Dowling J, Dayan S, Kerr PG, Holdsworth SR, Kitching AR, Summers SA (2014) Histopathologic and clinical predictors of kidney outcomes in ANCA-associated vasculitis. Am J Kidney Dis 63(2):227–235. https://doi.org/10.1053/j.ajkd.2013.08.025

    Article  PubMed  Google Scholar 

  28. Menez S, Hruskova Z, Scott J, Cormican S, Chen M, Salama AD, Alasfar S, Little MA, Safrankova H, Honsova E et al (2018) Predictors of renal outcomes in sclerotic class anti-neutrophil cytoplasmic antibody glomerulonephritis. Am J Nephrol 48(6):465–471. https://doi.org/10.1159/000494840

    Article  PubMed  CAS  Google Scholar 

  29. Bitton L, Vandenbussche C, Wayolle N, Gibier JB, Cordonnier C, Verine J, Humez S, Bataille P, Lenain R, Ramdane N et al (2020) Tubulointerstitial damage and interstitial immune cell phenotypes are useful predictors for renal survival and relapse in antineutrophil cytoplasmic antibody-associated vasculitis. J Nephrol 33(4):771–781. https://doi.org/10.1007/s40620-019-00695-y

    Article  PubMed  CAS  Google Scholar 

  30. Ni A, Chen L, Lan L, Wang Y, Ren P, Zhu Y, Xu Y, Shen X, Zhou Q, Huang X et al (2023) Validation of the antineutrophil cytoplasmic antibody renal risk score and modification of the score in a Chinese cohort with a majority of myeloperoxidase-positive patients. J Rheumatol 50(5):662–670. https://doi.org/10.3899/jrheum.220818

    Article  PubMed  CAS  Google Scholar 

  31. Haroun MK, Stone JH, Nair R, Racusen L, Hellmann DB, Eustace JA (2002) Correlation of percentage of normal glomeruli with renal outcome in Wegener’s granulomatosis. Am J Nephrol 22(5-6):497–503. https://doi.org/10.1159/000065283

    Article  PubMed  Google Scholar 

  32. de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, Jayne DR, Gaskin G, Rasmussen N, Noël LH, Ferrario F, Waldherr R, Hagen EC et al (2006) Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: a prospective analysis of 100 patients with severe renal involvement. J Am Soc Nephrol 17(8):2264–2274. https://doi.org/10.1681/asn.2005080870

    Article  PubMed  Google Scholar 

  33. Wilson PC, Kashgarian M, Moeckel G (2018) Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis. Clin Kidney J 11(2):207–218. https://doi.org/10.1093/ckj/sfx093

    Article  PubMed  Google Scholar 

  34. Geetha D, Sethi S, De Vriese AS, Specks U, Kallenberg CGM, Lim N, Spiera R, St Clair EW, Merkel PA, Seo P et al (2017) Interstitial immunostaining and renal outcomes in antineutrophil cytoplasmic antibody-associated glomerulonephritis. Am J Nephrol 46(3):231–238. https://doi.org/10.1159/000480443

    Article  PubMed  CAS  Google Scholar 

  35. Hruskova Z, Honsova E, Berden AE, Rychlik I, Lanska V, Zabka J, Bajema IM, Tesar V (2014) Repeat protocol renal biopsy in ANCA-associated renal vasculitis. Nephrol Dial Transplant 29(9):1728–1732. https://doi.org/10.1093/ndt/gfu042

    Article  PubMed  Google Scholar 

  36. Neumann I, Kain R, Regele H, Soleiman A, Kandutsch S, Meisl FT (2005) Histological and clinical predictors of early and late renal outcome in ANCA-associated vasculitis. Nephrol Dial Transplant 20(1):96–104. https://doi.org/10.1093/ndt/gfh563

    Article  PubMed  Google Scholar 

  37. Hilhorst M, Wilde B, van Breda VP, van Paassen P, Cohen Tervaert JW (2013) Estimating renal survival using the ANCA-associated GN classification. J Am Soc Nephrol 24(9):1371–1375. https://doi.org/10.1681/asn.2012090912

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Wang RX, Wang JW, Li ZY, Chen SF, Yu XJ, Wang SX, Zhang F, Xiong ZY, Bi SH, Wang Y et al (2023) A modified renal risk score for Chinese patients with antineutrophil cytoplasmic antibody-associated vasculitis. BMC Med 21(1):45. https://doi.org/10.1186/s12916-023-02755-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. van Daalen E, Ferrario F, Noël LH, Waldherr R, Hagen EC, Bruijn JA, Bajema IM (2015) Twenty-five years of RENHIS: a history of histopathological studies within EUVAS. Nephrol Dial Transplant 30(Suppl 1):i31–i36. https://doi.org/10.1093/ndt/gfv035

    Article  PubMed  CAS  Google Scholar 

  40. Uchida T, Ichinose K, Yamashita A, Muta K, Kitamura M, Sato S, Iwamoto N, Nishino T, Kawakami A (2023) Evaluation of a renal risk score for Japanese patients with ANCA-associated glomerulonephritis in a multi-center cohort study. Front Immunol 14:1141407. https://doi.org/10.3389/fimmu.2023.1141407

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Data availability statement

The data are available from the corresponding author upon reasonable request.

Funding

Natural Foundation of Zhejiang LQ21H050004 (WK); National Natural Foundation of China 82000635 (WK); Primary Research and Development Plan of Zhejiang Province 2020C03034 (FH).

Author information

Author notes

  1. Weiwei Kong and Jiahui Wang contributed equally to the study.

Authors and Affiliations

  1. Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine; Institute of Nephrology, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, 79 Qingchun Road, Zhejiang, 310003, Hangzhou, China

    Weiwei Kong, Jiahui Wang, Meifang Wang, Anqi Ni, Xiaohan Huang, Liangliang Chen, Qin Zhou, Huiping Wang, Jianghua Chen & Fei Han

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  1. Weiwei Kong
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  2. Jiahui Wang
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  10. Fei Han
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Contributions

Conception and design: Weiwei Kong, Jiahui Wang, Fei Han; data acquisition: Anqi Ni, Xiaohan Huang, Liangliang Chen, Meifang Wang, Qin Zhou, Huiping Wang; analysis and interpretation of data: Weiwei Kong; drafting the article: Jiahui Wang, Weiwei Kong; revising the article: Fei Han, Jianghua Chen; final approval of submitted version: Fei Han.

Corresponding author

Correspondence to Fei Han.

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Ethics approval and consent to participate

This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (No. [2020]571, approval date 20200923). All procedures were followed by the ethical standards of the responsible committee on human experimentation (institutional and national) and with the World Medical Association Declaration of Helsinki. Consent was obtained from all patients to be included in the study.

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Kong, W., Wang, J., Wang, M. et al. The correlation of interstitial change with renal prognosis in patients with myeloperoxidase-ANCA-associated glomerulonephritis: a single-center retrospective analysis. Clin Rheumatol 43, 377–386 (2024). https://doi.org/10.1007/s10067-023-06753-y

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