Glomerular Immune Deposition in MPO-ANCA Associated Glomerulonephritis Is Associated With Poor Renal Survival.

Rapidly progressive glomerulonephritis caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is typically characterized as pauci-immune glomerulonephritis. However, immune complex (IC) deposition in the glomerulus has been reported in a growing number of studies. Here, we assess the presence of glomerular immune deposits alongside renal outcome in myeloperoxidase (MPO)-ANCA associated glomerulonephritis (MPO-ANCA GN). Clinical and histopathologic characteristics of 97 patients with MPO-ANCA GN classified by renal biopsy from January 2008 to December 2019 were extracted retrospectively from electronic medical records. The extent of immune deposits in the kidney (C3, C4, C1q, IgA, IgG, IgM) at diagnosis were analyzed by immunofluorescence (IF). Patients were followed up for a median period of 15 months. The response to treatment and outcomes of renal and histological lesion changes were also assessed. In our study, 41% (40/97) of patients showed positive IF (≥2+) for at least one of the six immunoglobulin or complement components tested. Patients with IC deposits showed higher levels of serum creatinine (p=0.025), lower platelet counts (p=0.009), lower serum complement C3 (sC3) (≤790 ml/L) (p=0.013) and serum IgG (p=0.018) than patients with pauci-immune (PI) deposition at diagnosis. End-stage renal disease was negatively associated with eGFR (HR 0.885, 95% CI 0.837 to 0.935, p<0.0001), platelet count (HR 0.996, 95% CI 0.992 to 1.000, p=0.046) and serum globulin (HR 0.905, 95% CI 0.854 to 0.959, p=0.001). Patients with lower sC3 levels showed a worse renal outcome than the patients with normal sC3 at diagnosis (p=0.003). Analysis of the components of the renal deposits found that patients with IgG deposits exhibited a poorer renal outcome compared to patients that were IgG negative (p=0.028). Moreover, Bowman's capsule rupture occurred less frequently in patients with IgM deposition compared with IgM negative counterparts (p=0.028). Vascular lesions and granuloma-like lesions had been seen more frequently in cases with IgA deposition than those without IgA deposition (p=0.03 and 0.015, respectively). In conclusion, patients with immune complex deposits in the kidney showed less platelet count, lower sC3 and sIgG levels, and higher serum creatinine levels. Patients with low sC3 at initial and with continued low sC3 during the treatment displayed a trend toward poorer kidney survival. Moreover, the IC group showed a worse renal outcome than the PI group, further enforcing the present strategy of introducing complement targeted therapies in AAV.

Lin W ，Shen C ，Zhong Y ，Ooi JD ，Eggenhuizen P ，Zhou YO ，Luo H ，Huang J ，Chen JB ，Wu T ，Meng T ，Xiao Z ，Ao X ，Peng W ，Tang R ，Yin H ，Xiao X ，Zhou Q ，Xiao P ... -  《Frontiers in Immunology》

Outcome Predictors of Biopsy-Proven Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis.

To determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN). A total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. All 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups (p < 0.001) and significantly lower in the sclerotic group (p < 0.05). In addition, disease histopathologically classified as sclerotic (p = 0.044), high serum creatinine level (≥320 μmol/L, p < 0.001), low albumin (<30 g/L, p = 0.024) and hemoglobin level (<90 g/L, p = 0.044) were associated with a greater risk of ESRD. After follow-up, 70 (62.5%) of 112 patients survived. Old age (≥60 years, p = 0.018) and low serum albumin (<30 g/L, p = 0.006) was significant risk factor for patient survival. Among patients with MPO-ANCA-GN, those with poor renal function, disease histopathologically classified as sclerotic, and lower albumin and hemoglobin levels were risk factors for ESRD, while older age and low serum albumin level were associated with a greater risk for all-cause mortality.

Ge Y ，Yang G ，Yu X ，Sun B ，Zhang B ，Yuan Y ，Zeng M ，Wang N ，Mao H ，Xing C ... -  《Frontiers in Immunology》

Antineutrophil cytoplasmic antibody-associated glomerulonephritis with immunoglobulin deposition.

Hirose O ，Itabashi M ，Takei T ，Honda K ，Nitta K ... -  《-》

ANCA-associated crescentic glomerulonephritis with immune complex deposits.

Sumida K ，Ubara Y ，Nomura K ，Hoshino J ，Suwabe T ，Hiramatsu R ，Hasegawa E ，Hayami N ，Yamanouchi M ，Sawa N ，Takemoto F ，Takaichi K ，Ohashi K ... -  《CLINICAL NEPHROLOGY》

The Clinicopathologic Spectrum of Rapidly Progressive Glomerulonephritis Based on Glomerular Immune Deposition and Antineutrophil Cytoplasmic Antibody.

Han F ，Chen L ，Le J ，Choong P ，Xu Y ，Wang H ，Chen J ... -  《-》