membranous nephropathy
DESCRIPTION
Membranous GN, presentation, diagnosis and update managementTRANSCRIPT
Membranous GN
Primary (75%) & secondary. Commonest form in adults 33%. Secondary :
Collagen vascular disease SLE 10 – 20 % ,Rh.arthritis,dermatomyosiltis,
thyroid disease, ankylosing spondylitis,MCD etc……
Infection : HIV, HB, C & G,
syphilis,malaria,shistosomiasis.leprosy,filariasis etc….
Drugs like captopril , gold, penicillamine etc…
Chemicals like formaldehyde. Tumors of solid organs. Familial , MS & sarcoidosis. Graft versus host disease chronic type, De novo in allograft resulting in up to
50% loss of graft in 1.5 – 2 % Recurrence in graft 3-7% after
10/12,CRF in 4ys.
Immuonological disease with subepithelial AgAb complex deposition.
C5b-C9 is a diagnostic test for following activity.
Male : female 2:1 Peak incidence around 4th & 5th
decades. 60 – 70 % NS 20 – 30 % spontaneous remission. 20 – 30 % progress to CRF. 70 – 90 % 10 ys renal survival.
Membranous Nephropathy
Saw tooth appearance
Saw tooth appearance
The immune deposits in membranous glomerulonephritis are located on the subepithelial, or outer aspect of the glomerular basement membrane as illustrated
Silver stain
The capillary walls are thickened and subepithelial "spikes" are present, representing elaboration of basement membrane between subepithelial immune deposits.
Electron microscopy
numerous subepithelial electron dense deposits separated by basement membrane, correlating with the "spikes" seen by light microscopy .
EM
EM of Membranous GN
Non-proliferative GN with CW thickening. The deposition is shown to have spikes
with trichrome stains late in the disease. Patchy or diffuse fibrosis with severity &
time. Deposition in places other than Sub.End
favors secondary types. IgG, IgM, IgA & light chains ê&ë.
Stages Normal Light microscopy appearance . Electron microscopy shows few deposition with
no basement memb. projections.Numerous deposits with projections.New extracellular material surround the
deposits.Dense deposits become electron lucent & the
BM become thick.Subendothelial disturbance & normal
S.Epithelail.
Deposits
Deposits Membrane
Epithelia
l cell
Urinary space
DepositDeposit
Capillary Lumen
Natural History of Membranous GNMost remit
24 – 40 % CRF
complications
Hypovolaemia with diuretics. Thrombosis . HTN . Hyperlipidaemia . Fluids overload. Serositis . IHD Infections .
SLE Differentiation between membranous nephropathy in SLE and the idiopathic type
Treatment Imuonsupression in MGN. Identify 2dry causes. Rate of progression : Low risk : 5%
proteinuria < 4 gm/day maintained for 6/12 Medium risk :
4 – 8 gm/day 6/12 steroid alone in not effective High risk :
abnormal renal function +/- proteinuria 6/12.
Treatment strategies
Specific immuonosupression Non-specific for proteinuria Treatment of secondary effects Prophylaxis
Specific therapy:
Corticosteroids:
Are not effective on their own especially for long term benefits.
Chlorambucil Ponticelli`s regimen :
steroids as pulse therapy initially 1 gm methylprednisolone IV for 3 days
0.5mg/kg/day chlorambucil for 1/12 alternating with
0.5 mg/kg/day prenisolone for 1/12
The two month cycle is repeated three times. At 10 ys 8 % Vs 40 % lost their RF.
Cyclophosphamide Different results in different studies.Falk & his group used pulsed Cyc with
pred for 2 ys showed no difference Non-randomized study showed the
reverse .
Cyclosporine
Improve proteinuria & preserve renal function in up to 2/3 of patients.
Some showed slow response of almost one year to a achieve remission .
Cattran et al showed that Cyc slowed progression of RF
May be the data is better in high risk groups with cyc than with other cytotoxic drugs.
Dose :3.5 – 4 mg/kg trough level of 150 – 200
The dose can be increased if no appropriate response.
Cell cept Weak data are available but showed
benefits in the form of protein excretion .
IV ImmuonoglobulinsBinds to complement hence decreasing
their activity .Dose :
0.4gm/day for three daysFollowed by :
0.4gm/day for 3 days at 3/52 intervalFollowed by :
0.4gm/day for 1day at 3/52 interval for 6 – 9/12
Azathioprine
Recommendations is that it is of no benefits awaiting large randomized trials.
NSAID
Can rarely cause MGN & lead to deterioration of the renal function.
Others
Rituximab Pentoxiphylline Tacrolimus
Nonspecific treatment
BP control ( ACEI ,ACERB, Non-dihydropyrdine )
Protein restriction 0.7 – 0.8 gm/kg + 1 gm for each gm loss of protein in urine.
Lipid control Diuretics Salt & water restriction Anticoagulation
Prophylaxis Guard against pneuomocystis cariniiBiphosphonates especially in
postmenopausal women .
Recommendations
Asymptomatic patients with non-nephrotic range proteinuria should be given general treatment & followed up.
Asymptomatic patients with nephrotic range proteinuria with controllable oedema should be observed for prolonged period since 65% have spontaneous remission.
Active therapy is indicated in those who are likely to progress :
- High S.Cr - Marked oedema - Proteinuria > 10gm/day- Evidence of scarring - Tubulointerstitial affection >10%- Thromboembolic disease