Could mesangial C3 deposition be an independent prognostic marker in immunoglobulin A nephropathy?

C3 deposition Complement IgA nephropathy Oxford classification

Journal

Journal of nephrology

ISSN: 1724-6059

Titre abrégé: J Nephrol

Pays: Italy

ID NLM: 9012268

Informations de publication

Date de publication:
10 Nov 2023

Historique:

received: 11 04 2023

accepted: 18 08 2023

medline: 10 11 2023

pubmed: 10 11 2023

entrez: 10 11 2023

Statut: aheadofprint

Résumé

Immunoglobulin A nephropathy (IgAN) is a common primary glomerulonephropathy. There is evidence that mesangial C3 deposition plays a role in the development of the disease. The aim of this study was to examine the effect of C3 deposition on the prognosis of IgAN patients. The study included 1135 patients with biopsy-confirmed IgAN from the database of the Turkish Nephrology Association Glomerular Diseases Working Group (TSN-GOLD). Patients were excluded from the study if they were aged < 18 or > 75 years or if C3 staining had not been performed in the immunofluorescent analysis. C3 deposition was defined as an immunofluorescence intensity of C3 ≥ 2 + within the mesangium. The primary endpoints were the development of end-stage renal disease, a 30% decrease in glomerular filtration rate compared to the basal value or an elevation in proteinuria to a nephrotic level (3.5 gr/day). Mesangial C3 deposition was observed in 603 (53.1%) patients. No statistically significant difference was found at baseline between the groups with and without mesangial C3 deposition, as for age, sex, BMI, proteinuria level, or the presence of hypertension. In the follow-up period with a mean duration of 78 months, no significant difference was found between the two groups regarding the primary endpoints (p = 0.43). A significant correlation between C3 deposition and segmental glomerulosclerosis (S1) according to the Oxford MEST-C classification was found (p = 0.001). Although a correlation was observed between mesangial C3 deposition and the S1 MEST-C classification, mesangial C3 deposition was not a prognostic factor in IgAN.

Sections du résumé

BACKGROUND BACKGROUND

METHOD METHODS

The study included 1135 patients with biopsy-confirmed IgAN from the database of the Turkish Nephrology Association Glomerular Diseases Working Group (TSN-GOLD). Patients were excluded from the study if they were aged < 18 or > 75 years or if C3 staining had not been performed in the immunofluorescent analysis. C3 deposition was defined as an immunofluorescence intensity of C3 ≥ 2 + within the mesangium. The primary endpoints were the development of end-stage renal disease, a 30% decrease in glomerular filtration rate compared to the basal value or an elevation in proteinuria to a nephrotic level (3.5 gr/day).

RESULTS RESULTS

Mesangial C3 deposition was observed in 603 (53.1%) patients. No statistically significant difference was found at baseline between the groups with and without mesangial C3 deposition, as for age, sex, BMI, proteinuria level, or the presence of hypertension. In the follow-up period with a mean duration of 78 months, no significant difference was found between the two groups regarding the primary endpoints (p = 0.43). A significant correlation between C3 deposition and segmental glomerulosclerosis (S1) according to the Oxford MEST-C classification was found (p = 0.001).

CONCLUSION CONCLUSIONS

Although a correlation was observed between mesangial C3 deposition and the S1 MEST-C classification, mesangial C3 deposition was not a prognostic factor in IgAN.

Identifiants

DOI: 10.1007/s40620-023-01770-1 PMID: 37947938

pubmed: 37947938

doi: 10.1007/s40620-023-01770-1

pii: 10.1007/s40620-023-01770-1

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

Références

Pattrapornpisut P, Avila-Casado C, Reich HN (2021) IgA nephropathy: core curriculum 2021. Am J Kidney Dis 78(3):429–441

doi: 10.1053/j.ajkd.2021.01.024 pubmed: 34247883

McGrogan A, Franssen CF, de Vries CS (2011) The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant 26(2):414–430

doi: 10.1093/ndt/gfq665 pubmed: 21068142

Gutiérrez E, Zamora I, Ballarín JA, Arce Y, Jiménez S, Quereda C et al (2012) Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol 23(10):1753–1760

doi: 10.1681/ASN.2012010063 pubmed: 22956820 pmcid: 3458461

Floege J, Amann K (2016) Primary glomerulonephritides. Lancet 387(10032):2036–2048

doi: 10.1016/S0140-6736(16)00272-5 pubmed: 26921911

Berger J, Hinglais N (1968) Intercapillary deposits of IgA-IgG. J Urol Nephrol (Paris) 74(9):694–695

pubmed: 4180586

Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S et al (2009) The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 76(5):534–545

doi: 10.1038/ki.2009.243 pubmed: 19571791

Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M et al (2017) Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int 91(5):1014–1021

doi: 10.1016/j.kint.2017.02.003 pubmed: 28341274

Suzuki H, Suzuki Y (2018) Murine models of human IgA nephropathy. Semin Nephrol 38(5):513–520

doi: 10.1016/j.semnephrol.2018.05.021 pubmed: 30177023

Maillard N, Wyatt RJ, Julian BA, Kiryluk K, Gharavi A, Fremeaux-Bacchi V et al (2015) Current understanding of the role of complement in IgA nephropathy. J Am Soc Nephrol 26(7):1503–1512

doi: 10.1681/ASN.2014101000 pubmed: 25694468 pmcid: 4483595

Nasri H, Sajjadieh S, Mardani S, Momeni A, Merikhi A, Madihi Y et al (2013) Correlation of immunostaining findings with demographic data and variables of Oxford classification in IgA nephropathy. J Nephropathol 2(3):190–195

pubmed: 24475448 pmcid: 3891132

Wu L, Liu D, Xia M, Chen G, Liu Y, Zhu X et al (2021) Immunofluorescence deposits in the mesangial area and glomerular capillary loops did not affect the prognosis of immunoglobulin a nephropathy except C1q:a single-center retrospective study. BMC Nephrol 22(1):43

doi: 10.1186/s12882-021-02237-w pubmed: 33514328 pmcid: 7845044

Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ et al (2007) Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. PLoS Med 4(10):e297

doi: 10.1371/journal.pmed.0040297 pubmed: 17941715 pmcid: 2020496

Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y et al (2021) New creatinine- and cystatin C-Based equations to estimate GFR without race. N Engl J Med 385(19):1737–1749

doi: 10.1056/NEJMoa2102953 pubmed: 34554658 pmcid: 8822996

Kim SJ, Koo HM, Lim BJ, Oh HJ, Yoo DE, Shin DH et al (2012) Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy. PLoS One 7(7):e40495

doi: 10.1371/journal.pone.0040495 pubmed: 22792353 pmcid: 3391269

Levey AS, Inker LA, Matsushita K, Greene T, Willis K, Lewis E et al (2014) GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the national kidney foundation and the US food and drug administration. Am J Kidney Dis 64(6):821–835

doi: 10.1053/j.ajkd.2014.07.030 pubmed: 25441437

Coppo R, Peruzzi L, Amore A, Piccoli A, Cochat P, Stone R et al (2007) IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria. J Am Soc Nephrol 18(6):1880–1888

doi: 10.1681/ASN.2006040347 pubmed: 17513327

Xie M, Zhu Y, Wang X, Ren J, Guo H, Huang B et al (2022) Predictive prognostic value of glomerular C3 deposition in IgA nephropathy. J Nephrol. https://doi.org/10.1007/s40620-022-01363-4

doi: 10.1007/s40620-022-01363-4 pubmed: 35994232

Nam KH, Joo YS, Lee C, Lee S, Kim J, Yun HR et al (2020) Predictive value of mesangial C3 and C4d deposition in IgA nephropathy. Clin Immunol 211:108331

doi: 10.1016/j.clim.2019.108331 pubmed: 31899330

Katafuchi R, Nagae H, Masutani K, Tsuruya K, Mitsuiki K (2019) Comprehensive evaluation of the significance of immunofluorescent findings on clinicopathological features in IgA nephropathy. Clin Exp Nephrol 23(2):169–181

doi: 10.1007/s10157-018-1619-6 pubmed: 30066158

Park S, Kim HW, Park JT, Chang TI, Kang EW, Ryu DR et al (2020) Relationship between complement deposition and the Oxford classification score and their combined effects on renal outcome in immunoglobulin A nephropathy. Nephrol Dial Transplant 35(12):2103–2137

doi: 10.1093/ndt/gfz161 pubmed: 31377783

Coppo R, Troyanov S, Bellur S, Cattran D, Cook HT, Feehally J et al (2014) Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int 86(4):828–836

doi: 10.1038/ki.2014.63 pubmed: 24694989 pmcid: 4184028

Herzenberg AM, Fogo AB, Reich HN, Troyanov S, Bavbek N, Massat AE et al (2011) Validation of the Oxford classification of IgA nephropathy. Kidney Int 80(3):310–317

doi: 10.1038/ki.2011.126 pubmed: 21544062

Alamartine E, Sauron C, Laurent B, Sury A, Seffert A, Mariat C (2011) The use of the Oxford classification of IgA nephropathy to predict renal survival. Clin J Am Soc Nephrol 6(10):2384–2388

doi: 10.2215/CJN.01170211 pubmed: 21885791 pmcid: 3359557

Hotta O, Furuta T, Chiba S, Tomioka S, Taguma Y (2002) Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis 39(3):493–502

doi: 10.1053/ajkd.2002.31399 pubmed: 11877568

Luciano RL, Moeckel GW (2019) Update on the native kidney biopsy: core curriculum 2019. Am J Kidney Dis 73(3):404–415

doi: 10.1053/j.ajkd.2018.10.011 pubmed: 30661724