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Observational Study
. 2023 Aug 1;18(8):1031-1040.
doi: 10.2215/CJN.0000000000000193. Epub 2023 Jun 7.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease

Anis Chaba  1 , Arnaud Devresse  2 , Vincent Audard  3   4 , Jean Jacques Boffa  5 , Alexandre Karras  6 , Claire Cartery  7 , Clément Deltombe  8 , Jonathan Chemouny  9 , Claudine Contamin  10 , Cecile Courivaud  11 , Simon Duquennoy  12 , Hugo Garcia  13 , Dominique Joly  14 , Nabila Goumri  15 , Guillaume Hanouna  16 , Jean Michel Halimi  17 , Emmanuelle Plaisier  18 , Mohamed Hamidou  19 , Cédric Landron  20 , David Launay  21 , Celine Lebas  22 , Mathieu Legendre  23 , Agathe Masseau  19 , Alexis Mathian  24 , Lucile Mercadal  13 , Nathalie Morel  24 , Prisca Mutinelli-Szymanski  17 , Sylvain Palat  25 , Jean-Loup Pennaforte  26 , Marie Noelle Peraldi  27 , Agnieszka Pozdzik  28 , Nicolas Schleinitz  29 , Olivier Thaunat  30 , Dimitri Titeca-Beauport  31 , Charlotte Mussini  32 , Sonia Touati  33 , Eric Prinz  34 , Anne Laure Faller  35 , Sarah Richter  35 , Eve Vilaine  36 , Sophie Ferlicot  32 , Clarissa Von-Kotze  37 , Julie Belliere  38 , Jerome Olagne  39 , Rafik Mesbah  40 , Renaud Snanoudj  1 , Mathilde Nouvier  41 , Mikael Ebbo  29 , Mohamad Zaidan  1
Affiliations
Observational Study

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease

Anis Chaba et al. Clin J Am Soc Nephrol. .

Abstract

Background: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined.

Methods: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse.

Results: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD.

Conclusions: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

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Conflict of interest statement

V. Audard reports consultancy for, honoraria from, and advisory or leadership roles on Advisory boards for Addmedica, Alnylam, AstraZeneca, Bayer, and Vifor pharma. J.J. Boffa reports consultancy for AstraZeneca, Bayer, BMS, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Otsuka, Travere, and Vifor pharma; honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Otsuka, and Vifor pharma; and advisory or leadership roles for AstraZeneca, Bayer, BMS, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Otsuka, Travere, and Vifor pharma. J. Chemouny reports consultancy for AstraZeneca. A. Devresse reports consultancy for and advisory or leadership roles for Alnylam Pharmaceuticals and Merck. S. Duquennoy reports employment with Fondation AUB SANTE. J.M. Halimi reports consultancy for Alexion, AstraZeneca, Bayer, Boehringer Ingelheim France, Servier, and Vifor Fresenius; research funding from AstraZeneca; and honoraria from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim France, MSD, Sanofi, Servier, and Vifor. D. Joly reports honoraria from AstraZeneca and Bayer. A. Karras reports consultancy for Alnylam, GlaxoSmithKline, Novartis, Otsuka, Vifor; honoraria from AstraZeneca, Bohringer-Ingelheim, GlaxoSmithKline, Novartis, Otsuka, Pfizer, and Vifor; advisory or leadership roles for Novartis, Otsuka, and Vifor; and speakers bureau for AstraZeneca, Boehringer-Ingelheim, Otsuka, Pfizer, and Vifor. A. Mathian reports consultancy for AstraZeneca, GlaxoSmithKline, Novartis, and Otsuka; honoraria from AstraZeneca, GlaxoSmithKline, Novartis, and Otsuka; advisory or leadership role for AstraZeneca; and speakers bureau for AstraZeneca, GlaxoSmithKline, and Otsuka. L. Mercadal reports honoraria for Congress travel and hotel in France and reports advisory or leadership roles for nephrologie thérapeutique review board and Société francophone de néphrologie dialyse transplantation. J. Olagne reports serving on speakers bureau for GlaxoSmithKline. S. Palat reports employment with and advisory or leadership role for Janssen Cilag. E. Plaisier reports employment with AURA PARIS. O. Thaunat reports consultancy for AstraZeneca, Biotest, and Novartis; research funding from bioMérieux, BMS, and Immucor; honoraria from Astellas, Biotest, and Novartis; and advisory or leadership role for ESOT. E. Vilaine reports consultancy for and honoraria from AstraZeneca. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flow chart. ACR, American College of Rheumatology; EULAR, European League Against Rheumatism Classification Criteria.
Figure 2
Figure 2
Typical kidney pathology in IgG4-TIN. (A) Light microscopic kidney biopsy findings in an IgG4-TIN patient with extensive interstitial fibrosis, tubular atrophy, and interstitial inflammation (trichrome stain, magnification ×55, scale bar=200 μm). (B) High-power view of lymphoplasmacytic infiltrate within the kidney interstitium with interlacing fibrils of storiform fibrosis (Periodic acid–Schiff stain, magnification ×400, scale bar=20 μm). (C) Typical storiform fibrosis in IgG4-TIN (periodic acid-methenamine silver stain, magnification ×200, scale bar=50 μm). Lymphocytes and plasma cells are encircled by collagenous tissue and diffuse fibrosis. (D) Immunohistochemistry for IgG4 showing numerous interstitial IgG4-positive plasma cells (magnification ×400, scale bar=20 μm). IgG4-TIN, IgG4-related tubulointerstitial nephritis. Images courtesy of S. Ferlicot, Bicêtre University Hospital, France. Figure 2 can be viewed in color online at www.cjasn.org.
Figure 3
Figure 3
Relapse risk. (A–C) Kaplan–Meier survival estimates of relapse-free survival according to the presence of (A) ANCA; (B) complement concentration; and (C) first-line rituximab therapy. (D) Violin plot of the number of organs involved according to relapse occurrence. Figure 3 can be viewed in color online at www.cjasn.org.
See this image and copyright information in PMC

Comment in

  • IgG4-Related Kidney Disease.
    Peyronel F, Vaglio A. Peyronel F, et al. Clin J Am Soc Nephrol. 2023 Aug 1;18(8):994-996. doi: 10.2215/CJN.0000000000000235. Epub 2023 Jul 7. Clin J Am Soc Nephrol. 2023. PMID: 37418275 Free PMC article. No abstract available.

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