Nephrotic Syndrome – Minimal Change Disease (MCD)

• Def  massive proteinuria w/o any structural changes on light microscopy

• Most common NS in kids

• 2 peak ages NOT b/w 10-60 yo (any other age) (except in 20-39 yo w/ Hodgkins)

  • kids  2-6 yo [MOST COMMON]

  • elderly  60-70 yo

• Assoc w/ HLA-DR7 (2000exam) or HLA-B12 (Harrison’s)?

• Pathogenesis 

  • 1^st mech  circulating factors  neutralize negative charge of BM &/or abnormality of T-cell function.

  • 2^nd mech  suspected b/c  incident of MCD in Hodgkin’s lymphoma  T-cells  production of lymphokines BM permeability

  • LM & IF  no  in glomerulus

  • EM  effacement of foot processes (absence of slit diaphragm between them)  is a REACTION to proteinuria

• Clinically 

  • 2-6 yo Boys (2:1)  present in 1 of 2 ways 

    • Full-blown NS w/ massive proteinuria, hyperlipidemia, edema (& anasarca)

    • Complications of NS (see above)

  • 1/3  preceding upper respiratory infx or vaccination

  • Renal fn & BP  initially normal

  • 1/3  present w/ small GFR  b/c hypovolemia

  • Hodgkin’s lymphoma assoc’d w/ MCD in 20-30 yo’s

  • Labs massive selective proteinuria in 85% of pts (UNIQUE among NS-causers)

    • Circulation immune complexes  found in 75% but w/ NO BM deposition

• Prognosis  good outcome  b/c 25-40% spontaneous remission  BUT 50% infreq’ly relapse

• Mortality

  • w/o corticosteroids  50% in 5yrs

  • w/ tx  7- 12%  If responsive to tx  <2%

• Prednisone therapy 

  • 60mg/m²/day for kids

  • 2mg/kg/day for adults

  • course  daily for 4 wks  Followed by every other day for next 4 wks  discontinue in 6 mos

  • results 

    • 90% of kids respond in 4 wks

    • 90% of adults respond in 8 weeks

  • 10% are steroid resistant   immunosuppressive tx  cyclophosphamide (causes hemorrhagic cyctitis, certain malignancies) OR chloroambucil

  • 50% who respond to steroid tx  free of proteinuria or occasional rare relapse

  • other 50%  steroid-dependent OR frequent relapsers (>2 relapses/year)

Category: Nephrology Notes