Membranoproliferative glomerulonephritis (MPGN) is characterized by three histopathologic findings: proliferation of mesangial and endothelial cells, thickening of peripheral capillary walls, and mesangial interposition into capillary walls. It can present with asymptomatic proteinuria and hematuria, nephrotic syndrome, acute nephritic syndrome, or recurrent gross hematuria. Treatment involves immunosuppression, antiplatelet agents, anticoagulants, and anti-inflammatory drugs. Recurrent disease is common after kidney transplantation.

1. Membranoproliferative
GlomeruloNephritis : a pattern
of rose or fire
By
Salwa Mahmoud Elwasif, M.D.
Fellow of Internal Medicine and Nephrology
Urology and Nephrology Center
Mansoura University

2. Nephrology
Kidney disease
Glomerular
proliferative
Non-
proliferative
Tubules interstitium Vascular

6. The reality

9. MPGN pattern:
Three characteristic histopathologic findings:
• Proliferation of mesangial and endothelial cells and
expansion of the mesangial matrix
• Thickening of the peripheral capillary walls by subendothelial
immune deposits and/or intramembranous dense deposits
• Mesangial interposition into the capillary wall, giving rise to a
double-contour or tram-track appearance on light
microscopy

10. Epidemiology
• 6-12% of US patients receiving renal
biopsies to evaluate glomerular diseases.
• 7% of children and 12% of adults with
idiopathic nephrotic syndrome.

11. Racial, sexual, and age differences
• predominantly affects the white population.
• Type I:
• Type II:

12. Prognosis
Predictors for poor prognosis:
• Nephrotic syndrome
• hypertension at presentation
• low GFR at 1 year
• older age.

13. Histologic characteristics of poor prognosis
• crescent formation
• interstitial fibrosis
• tubular atrophy
• multiple sclerotic glomeruli
hypocomplementemia is not a predictor of
disease severity or prognosis.

17. Traditional classification

18. Traditional classification

19. Traditional classification

20. Pathophysiology
• C1 x Ag/Ab
• C4b2a
Classic
pathway
• C3 and factors B and D
• C3b Bb
Alternative
pathway
Factor H
Factor l
-- --- --
-
- -
-

21. nephritic antibodies
Nephritic Factor of the classic pathway
•stabilizes the classic pathway C3 convertase C4b,2a.
Nephritic Factor of the amplification loop
• It is autoantibody to C3b,Bb
• preventing degradation, resulting in complement activation and
chronic consumption of C3.
Nephritic Factor of the terminal pathway
• stabilizes the alternative pathway properdin-dependent C3/C5
convertase (C3Bb2,Bb,P) and leads to C3 activation and
consumption.
• The consumption of C3 caused by NFt is much slower than that
caused by NFa.
• NFt also activates the terminal complement components forming
C5b-C9, the membrane attack complex

22. MPGN Type l
+
circulating
immune
complexes
•nature of the antigen,
• size of complexes,
•type and charge on
antibodies,
•local glomerular
factors

23. MPGN Type ll
• No circulating immune complexes
• NFa is present in 80% of patients with DDD
• Adipocytes produce adipsin, which is
identical to complement factor D
• NFa causes a lysis of adipocytes that
produce adipsin

24. Hypocomplementemia
• Low C3 levels in 75% of patients
• Causes of Hypocomplementemia
•increased catabolism
•decreased C3 synthesis.

25. Hypocomplementemia
plays a role in
initiating glomerular
inflammation and
injury.
no relation to the
clinical course or
prognosis of MPGN

28. Daccueil et al, AJKD © National Kidney Foundation.

32. Etiology
 Immune complex–mediated disease
•Idiopathic
•Chronic infections
•Autoimmune diseases
 Chronic and recovered thrombotic microangiopathies
 Paraprotein deposition diseases
 Malignant neoplasms

33. Clinical picture
•Asymptomatic proteinuria and hematuria detected on routine urinalysis (23-
30%), prompting further investigations
•Nephrotic syndrome (42-67%): Periorbital or dependent edema may develop in
patients with nephritic or nephrotic presentations; anasarca is present in a few
patients
•Acute nephritic syndrome (16-30%): Patients with an acute nephritic
presentation may develop a decrease in urine output (oliguria)
•Recurrent episodes of gross hematuria (10-20%): Patients may have episodes
of gross hematuria similar to those observed with IgA nephropathy—these
episodes are usually associated with upper respiratory infections
•Azotemia: Patients may develop acute kidney injury with the acute nephritic
syndrome, which usually correlates with crescentic transformation on histology;
other patients may present with advanced chronic renal insufficiency

35. D.D
• Acute Glomerulonephritis
• IgA Nephropathy
• Lupus Nephritis
• Poststreptococcal Glomerulonephritis
• Rapidly Progressive Glomerulonephritis

36. Complications
• Secondary hypertension, edema, and infections
• Thromboembolism tendency
• Hyperlipidemia
• Recurrent disease after transplantation

38. Recurrent disease after
transplantation
• MPGN type I disease, 30-70% of which 30-40% lead to
graft failure.
• MPGN type II ranges from 50% to 100%; although
recurrences may be mild, eventually 50% of the grafts fail.
• MPGN type III are not known.
• Recurrent MPGN needs to be differentiated from
transplant glomerulopathy, which has a similar histology
but lacks immune deposits.

40. Treatment
• Immunosuppression
• Inhibiting platelet-induced injury with aspirin and
dipyridamole
• Minimizing glomerular fibrin deposition with
anticoagulants
• Use of steroidal and nonsteroidal anti-inflammatory
agents
https://emedicine.medscape.com/article/240056-medication