RPGN

1.Definition#

• Clinical syndrome of GN with progressive loss of renal function(over days-months)
  • =acute~subacute
  • 病理新月體定義與分類〔B&R 11e〕: 囊外細胞增生達 ≥2 層且覆蓋 >10-25% 圓周；新月體腎炎(crescentic GN) 定義為 ≥50% 腎絲球具新月體。分型：
    • Cellular(細胞性): >50% 為增生細胞，反應佳且具高可逆性，為積極免疫抑制治療之核心標靶
    • Fibrocellular(纖維細胞性): 10-50% 細胞且 >50%~<90% 為細胞外基質
    • Fibrous(纖維性): <10% 細胞且 >90% 為基質膠原纖維，屬不可逆瘢痕組織
  • Pathology參pathology-Extracapillary proliferative glomerulonephritis (crescentic)

2.Types#

• Anti-GBM antibody disease
• Immunocomplex
  • PSGN, IgA nephropathy, cryoglobulin, SLE/AIR, some idiopathic MGN(some Pts with MGN and crescent formation有ANCA(+) or anti-GBM(+), 不過不太清楚是不是MGN剛好concurrent AAV or anti-GBM disease)
• Pauci-immune
  • Could be ANCA(+) or ANCA(-)
  • 有時候有scattered small immune deposits in mesangium and glomerular capillary wall
  • Ab against lysosome-associated membrane protein 2 (LAMP-2)(曾報告>90%病人陽性, 但後續study未能重現, 目前存疑)
• Idiopathic
  • Immune complex but not fit any AIR disease(rare)
  • Or pauci-immune but ANCA(-) (<5% cases of crescent GN)
    • ANCA(-)者的systemic表現和ANCA(+)很相似(表示有相似的antigen or Ab只是未被檢驗出??disease早期??ANCA masked by circulating fragments of enzymatically degraded ceruloplasmin(?, ceruloplasmin是MPO的inhibitor)?; ANCA(-) pauci-immune crescent GN仍為GPA/MPA spectrum disease)

3.S/S#

• 大多insidious onset with initial presentation of fatigue and edema
  • 但也可以以acute, nephritis syndrome表現(如:PSGN...)
• Lab:多RPRF(診斷時Cre常>3), active sediments with variable proteinuria(多no nephrotic syndrome, 因為GFR↓↓↓, 不過若GFR未下降很多也可以有nephrotic syndrome)

4.Diagnosis#

• ANA, C3, C4, IgA, ASLO, cryoglobulin, ANCA, anti-GBM, renal biopsy...

5.Tx#

• According to the diagnosis
• 不過不論是哪種disease, 只給Steroid +/- AZA多無效
• 所以原則上Empirical要Pulse steroid + maintenance steroid + Endoxan/Rituximab +/- DFPP(especially if hemoptysis(+)) +/- IVIG
• 註:PEXIVAS(2020)後, pauci-immune ANCA者DFPP不再常規使用(見-ANCA disease); anti-GBM(+)或severe DAH者仍考慮DFPP
  • PJP 預防(Baktar): 使用 Endoxan 或 predonine ≥20mg/day 預期超過 1 個月者，治療伊始即應同步投予 Baktar 預防
  • If long term steroid use-->consider prophylactic Nystatin and Gaster/PPI and Ca/Vit.D/Bisphosphonate
• 即使是PSGN, 雖然no evidence of immunosuppressive Tx, 但若crescent >30%一樣可以考慮使用pulse steroid(不過其他有active infection的IRGN就不建議immunosuppressants)