Deciphering Three Predominant Biopsy-proved Phenotypes of IgG4-associated Kidney Disease: A Retrospective Study

Abstract

Abstract Background IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge. Methods We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022. Results The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A: 47.6%, group B: 30%, group C: 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A: 0.3 g/d, group B: 4.0 g/d, group C: 0.8 g/d, p < 0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A: 103.45 g/L, group B: 119.60 g/L, group C: 87.94 g/L, p < 0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death. Conclusions This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.