MCD/FSGS variant

GN約 5 分鐘3 個章節

Data from uptodate Minimal change variants: Mesangial proliferation: IgM nephropathy: C1q nephropathy

1.Idiopathic mesangial proliferative GN(may be with MCD, FSGS)#

Histology
本譜系部分個案活動期可測得circulating anti-nephrin Ab，緩解期下降〔PMID 34732507〕
- LM:focal(<50%) or diffuse(>50%) mesangial cell proliferation[non-specific; LN(fullhouse), IgA nephropathy(IgA, C3, lambda), mild or resolving PSGN(IgG, C3)也會如此, 不過Immunofluorescence則不同]
- Immunofluorescence microscopy:absence of immune deposits or (focal or diffuse IgM-containing deposits in the mesangial area)[no IgG/IgA]
  - 應該也有C3吧?
- EM:diffuse foot process fusion(if nephrotic syndrome者(MCD like)), no electron dense depositions
S/S
- 可Isolated hematuria
- 可gross or microscopic hematuria
  - 可follows a nonstreptococcal URI(似IgA nephropathy, 其實MCD也會after URI)
  - 常spontaneously resolve但也可persistent; renal prognosis很好
- Or nephrotic syndrome(more common)
  - 3-5% (Pts with idiopathic nephrotic syndrome) have mild diffuse mesangial cell proliferation but no FSGS by LM; EM多
    - showed relatively diffuse foot process fusion
      - >50% response to steroid within 8W and 剩下的也常 remission at 1yr
      - 所以有些像是severe MCD with more severe initial injury, leading to mesangial cell dysfunction and 比較慢recovery
  - 但10-30%Pts則像FSGS(proved by repeated biopsy)-->progressive renal insufficiency
  - 若steroid resistant==>可try Endoxan/CsA/MMF(no well trials)

Histology
- LM:MCD or FSGS or mesangial proliferative GN
- Immunofluorescence microscopy:prominent diffuse mesangial deposits of IgM and complement
- EM:electron dense deposits in the mesangium
  - 若有看到IgM deposits by immunofluorescence but no electron dense deposits by EM==>比較像是nonspecifically deposited onto an abnormally permeable GBM trapped in an area of glomerulosclerosis==>那這種情況就比較像MCD/FSGS with nonspecific IgM deposits而非IgM nephropathy
Tx response to steroid
- Responsive:dependent:resistant=1:1:1(所以prognosis比MCD差很多)
  - 20-35% ESRD in 5-15yrs
  - Other Tx as MCD/FSGS
- Bhasin等(Lab Invest 1978; PMID 355724)：定義為瀰漫性mesangial cell proliferation伴隨顯著mesangial IgM沉積與EM電子緻密物，臨床常呈類MCD表現但對steroid易依賴或抗藥〔PMID 355724〕
- Myllymäki等(Nephron Clin Pract 2006; PMID 16282696)：血清高C3及低IgG/C3比值與IgM nephropathy疾病進展及嚴重病理變化顯著相關〔PMID 16282696〕

Histology：【必考鑑別原則】C1q nephropathy 診斷前必須百分之百排除 SLE（ANA陰性、補體正常、無全身狼瘡表徵），否則一律視為潛在或不典型狼瘡性腎炎〔PMID 3875286〕
- Jennette & Hipp(AJKD 1985; PMID 3875286)：原初定義為廣泛mesangial C1q沉積伴EM電子緻密物，臨床多呈小兒/年輕成人steroid-resistant nephrotic syndrome，且無SLE臨床或血清學證據(ANA陰性、補體正常)〔PMID 3875286〕
- LM:MCD or FSGS or mesangial proliferative GN
- Immunofluorescence microscopy:prominent C1q deposits +/- IgG, IgM, C3
- EM:electron dense deposits(=有immunocomplex) in the mesangium
S/S:可nephrotic syndrome, 50% hematuria(尤其有mesangial proliferative GN者), 可no S/S
Tx則看LM像什麼(MCD or FSGS..., Tx as them)
- Prognosis也是有像MCD, 有像FSGS的...
- Vizjak等(JASN 2008; PMID 18650484)：C1q nephropathy分兩大類：(1) Podocytopathy型(MCD樣或FSGS，多表現為nephrotic syndrome，MCD樣者77% CR，FSGS者33%進展至ESRD)；(2) 免疫複合物型(proliferative GN，多表現為CKD或無症狀尿檢異常)〔PMID 18650484〕