Minimal Change Disease

  • ~10-15% of NS
  • 30-50% can remit without treatment but may take up to 2 years
  • Probably can progress to FSGS
  • Over 80% of adults with MCD are steroid responsive.
  • 50-70% of adult patients will relapse
  • 1/3 patients may become frequent relapsers or steroid dependent Waldman et al, cJASN 2007.
  • Rapid onset of nephrotic sydrome
  • 15% of adult cases are secondary: nonsteroidal anti-inflammatory drugs, lithium, and lymphoproliferative disorders
  • Hypertension (25%–50%), hematuria (20%–30%), and AKI ( ATN? )(20%–25%) are more common in adults
  • Rarely can lead to CKD, or even ESRD ( <5%)
  • Anticoagulation: lower risk but perhaps if resistant?

Typical Steroid Course

  • Remission in ~50% adults by 8 weeks, 75-95% by 16.
  • 1mg/kg, max 80mg po od - 4 weeks minimum, up to 16 weeks if waiting on remission
  • Run 2-4 weeks post remission
  • Reduce to achieve total treatment of 4-6 months
  • Remission is classically quite abrupt

Relapse

  • Common, 65-80%
  • Usually first 3-6 months post remission
  • Age <45 relapse more (?better immune system?)
  • 1st relapse - repeat pred course
  • 2 * courses in 6/months or 4/12 = frequent relapser
  • 10-30% are frequent relapses and 15-30% are steroid dependant
  • Probably reasonable to give ritux although weight of evidence us for cylophos. Ruggenenti et al JASN 2014
  • RTX (4 weekly doses of 375 mg/m2
  • Cyclophos po ~2mg/kg po od * 8-12 weeks. ( note dose adjusted by age & eGFR)
  • Partial remission is rare - rebiopsy for missed FSGS on bx?

Anti-Nephrin antibodies

Heres a pretty good freely filtered where the author Astrid Weins is interviewed - really enlightening ideas. Some conceptual highlights included

  • Fine granular IgG dusting on almost all MCD bxs !?
  • MCD-FSGS spectrum
  • ~30% of MCD disease have circulating anti-nephrin antibodies (NEPTUNE cohort)
  • Anti-nephrin is basically the perfect assault molecule vs slit diaphragm.
    • IgG is freely filtered - just zooms past the slit diagram, is continually replenished, hours of affinity perhaps, and it gets instagibbed. Slit diaphragm integrity disrupted.
    • Doesnt need to accumulate and cause immune complexs( unlike anti-PLAR2)
    • The antibody/antigen balance is probably very subtle and minor effects will shift clinical picture ( steroids etc)
    • Fastest responders seem to loose ab over days.
    • No antibodies in patients in remission.

The pathology of acute nephrotic syndrome in MCD

  • Effacement = nothing goes through = higher pressure
  • disrupted structure results in Bigger pore size
  • Nephrotic syndrome ramps up the pressure and overcomes the negative charge of the endothelium which allows negative albumin.
  • Therefore dont need to alter endothelium, just need to overcome it via ramping up pressure/pore size ( ?via nephrin -> actin cytoskeleton disruption)

Recurrance post tx

Rare. not sure how this fits with FSGS high recurrance.

Adult data here **

In rare cases Recurrance post tx of congenital nephrotic syndrome is thought to be driven by anti-nephrin abs ( and responds accordingly to b-cell depletion) re paediatrics, in congential (primary is typically AR vs NPHS1(nephrin)/NPHS2) nephrotic syn and tx:

  • Recurrance is rare in congential forms
  • Return of proteinuria is common in non congenital forms (80% of total)

Mintac

The mintac trial

  • Oral tacrolimus at 0.05 mg/kg twice daily vs or prednisolone at 1 mg/kg daily up to 60 mg daily.
  • The primary outcome was complete remission of nephrotic syndrome after 8 weeks of therapy.
  • Secondary outcomes included remission of nephrotic syndrome at 16 and 26 weeks, rates of relapse of nephrotic syndrome, and changes from baseline kidney function.

Mintac Protocol

  • Everyone got Acei, statin (if required)
  • Run tacro levels 6-8
  • At week 8, if inadequate clinical response, target blood trough level was increased to 9-12 ng/ml.
  • 12 weeks after achieving complete remission, tacrolimus doses were titrated down over 8 weeks and stopped.
  • Participants in prednisolone arm received an initial dose of 1mg/kg per day with a maximum dose of 60 mg/kg per day.
  • One week after achieving complete remission, the steroid dose was halved for 4-6 weeks then gradually reduced and stopped over a further 6 weeks. Patients received a minimum of 16 weeks prednisolone. Bone and gastric protection was with calcium carbonate/cholecalciferol (1000mg/800IU) two tablets daily and omeprazole 20mg daily
  • Complete remission was defined as uPCR <50 mg/mmol
  • Results non inferior

abtract by Pablo Garcia

Key Papers


Nature reviews Nephrology: MCD-FSGS spectrum

  • Early FSGS must have some early podocyte injury - some believe this is the same intial injury and FSGS is end game
  • Genetic / environmental factors

CJASN: nice review on clinical features of MCD