Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease
Authors: Chaba Anis , Devresse Arnaud , Audard Vincent , Boffa Jean Jacques , Karras Alexandre , Cartery Claire , Deltombe Clément , Chemouny Jonathan , Contamin Claudine , Courivaud Cecile , Duquennoy Simon , Garcia Hugo , Joly Dominique , Goumri Nabila , Hanouna Guillaume , Halimi Jean Michel , Plaisier Emmanuelle , Hamidou Mohamed , Landron Cédric , Launay David , Lebas Celine , Legendre Mathieu , Masseau Agathe , Mathian Alexis , Mercadal Lucile , Morel Nathalie , Mutinelli-Szymanski Prisca , Palat Sylvain , Pennaforte Jean-Loup , Peraldi Marie Noelle , Pozdzik Agnieszka , Schleinitz Nicolas , Thaunat Olivier , Titeca-Beauport Dimitri , Mussini Charlotte , Touati Sonia , Prinz Eric , Faller Anne Laure , Richter Sarah , Vilaine Eve , Ferlicot Sophie , Von-Kotze Clarissa , Belliere Julie , Olagne Jerome , Mesbah Rafik , Snanoudj Renaud , Nouvier Mathilde , Ebbo Mikael , Zaidan Mohamad 
Published: June 2023

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 m2 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 m2 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 m2. 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.