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1. Membranous Nephropathy
KDIGO 2021 Clinical Practice Guideline for the
Management of Glomerular Diseases
Mohammed Abdel Gawad MD Neph, ESENeph
Lecturer of Nephrology, School of Medicine, NewGiza University
Nephrology Consultant, Alexandria
Founder of NephroTube.com
Co-chair of AFRAN Web/Media Committee
ISN Education SoMe Team Member
drgawad@gmail.com
@Gawad_Nephro
October, 2022

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4. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

5. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

6. Membranous Nephropathy
• Glomerular disease:
• Nephrotic syndrome in 60% to 70%
• Normal or mildly elevated blood pressure at presentation
• Urine:
• Benign urinary sediment
• Nonselective proteinuria
Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.

7. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

8. Membranous Nephropathy
• Subepithelial Immune deposits of IgG and complement
Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.

9. Membranous Nephropathy
• Etiology:
Primary Secondary

10. Subepithelial deposits MN
Possible Mechanisms
Glassock RJ. N Engl J Med 2009;361:81-83.
Possible Mechanisms of the Formation of Subepithelial Deposits in Experimental Models of, and Patients with,
Membranous Nephropathy.

11. Subepithelial deposits MN
Possible Mechanisms
Glassock RJ. N Engl J Med 2009;361:81-83.
Possible Mechanisms of the Formation of Subepithelial Deposits in Experimental Models of, and Patients with,
Membranous Nephropathy.

12. Human Podocyte Antigens Phospholipase A2
Receptor

13. Human Podocyte Antigens
Thrombospondin type - 1 domain -
containing 7A (THSD7A)
• A transmembrane protein expressed on podocytes.
• Responsible Ab in 10% of primary MN with negative
anti-PLA2R Ab.
Gödel M et al. N Engl J Med 2015; 372:1073.
Iwakura T et al. PLoS One 2015; 10:e0138841.

15. Anti-PLA2R
Is it only related to primary MN?
J Am Soc Nephrol 22: 1137–1143, 2011.

16. Anti-PLA2R Titers Clinical Significance
• Highly suggestive of primary MN
• But does not exclude the coexistence of:
• hepatitis virus infection,
• malignancy,
• another associated rheumatologic or
inflammatory disease.
J Am Soc Nephrol 22: 1137–1143, 2011.
Serum complement
is usually normal in
primary MN

17. Serum PLA2R auto antibodies test is a
good +ve but not good -ve marker for
MN.
Anti-PLA2R Titers Clinical Significance

18. Diagnosis of membranous nephropathy (MN)

19. Diagnosis of membranous nephropathy (MN)

20. Membranous Nephropathy
• Etiology:
Primary Secondary

21. MEMBRANOUS NEPHROPATHY - DIAGNOSIS
Practice Point 3.1.2: Patients with MN should be evaluated for associated conditions, regardless
of whether antiPLA2R antibodies and/or anti-THSD7A antibodies are present or absent.
CXR or CT scan, look
for iron deficiency,
breast and colon
cancer screening, PSA
in adult males aged
>50–60 years.

23. Malignancy Screening
Frequency of screening
Cancer screening should continue for a period of
five to ten years after the diagnosis of MN
(since cancers associated with MN are typically diagnosed within
this time frame.)
Laurence H Beck, David J Salant. UpTodate. Oct 29, 2020.

24. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

25. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.5: Prophylactic anticoagulant therapy in patients with MN and nephrotic syndrome
should be based on an estimate of the risk of thrombotic events and the risk of bleeding complications
Assess risk of venous thrombosis and risk of bleeding
(http://www.med.unc.edu/gntools/).

26. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.5: Prophylactic anticoagulant therapy in patients with MN and nephrotic syndrome
should be based on an estimate of the risk of thrombotic events and the risk of bleeding complications
Assess risk of venous thrombosis and risk of bleeding
(http://www.med.unc.edu/gntools/).

27. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.5: Prophylactic anticoagulant therapy in patients with MN and nephrotic syndrome
should be based on an estimate of the risk of thrombotic events and the risk of bleeding complications
Assess risk of venous thrombosis and risk of bleeding
(http://www.med.unc.edu/gntools/).

28. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.5: Prophylactic anticoagulant therapy in patients with MN and nephrotic syndrome
should be based on an estimate of the risk of thrombotic events and the risk of bleeding complications
Assess risk of venous thrombosis and risk of bleeding
(http://www.med.unc.edu/gntools/).

29. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.5: Prophylactic anticoagulant therapy in patients with MN and nephrotic syndrome
should be based on an estimate of the risk of thrombotic events and the risk of bleeding complications
Assess risk of venous thrombosis and risk of bleeding
(http://www.med.unc.edu/gntools/).

30. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

31. MEMBRANOUS NEPHROPATHY - PROGNOSIS
Practice Point 3.2.1: In patients with MN, use clinical and laboratory criteria to assess the risk of
progressive loss of kidney function.

32. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

33. MEMBRANOUS NEPHROPATHY - TREATMENT
Practice Point 3.3.1: Considerations for treatment of patients with primary MN:
• All patients with primary MN and proteinuria should receive optimal supportive
care.
• Immunosuppressive therapy should be restricted to patients considered at risk for
progressive kidney injury.
Practice Point 3.3.3:
Immunosuppressive therapy
is not required in patients
with MN, nephrotic
syndrome, and normal eGFR,
unless at least one risk factor
for disease progression is
present or serious
complications of nephrotic
syndrome (e.g., AKI,
infections, thromboembolic
events) have occurred.

34. MEMBRANOUS NEPHROPATHY - TREATMENT
Practice Point 3.3.1: Considerations for treatment of patients with primary MN:
• All patients with primary MN and proteinuria should receive optimal supportive
care.
• Immunosuppressive therapy should be restricted to patients considered at risk for
progressive kidney injury.

35. MEMBRANOUS NEPHROPATHY - TREATMENT
Recommendation 3.3.1: For patients with MN and at least one risk factor for disease
progression, we recommend using rituximab or cyclophosphamide and alternate
month glucocorticoids for 6 months, or CNI-based therapy for ≥6 months, with the
choice of treatment depending on the risk estimate (1B).

36. MEMBRANOUS NEPHROPATHY - TREATMENT
Recommendation 3.3.1: For patients with MN and at least one risk factor for disease
progression, we recommend using rituximab or cyclophosphamide and alternate
month glucocorticoids for 6 months, or CNI-based therapy for ≥6 months, with the
choice of treatment depending on the risk estimate (1B).

37. MEMBRANOUS NEPHROPATHY - TREATMENT
Practice Point 3.3.4: Longitudinal monitoring of antiPLA2R antibody levels at 6 months
after start of therapy may be useful for evaluating treatment response in patients
with MN, and can be used to guide adjustments to therapy.
Some centers will measure anti- PLA2R antibodies at month 3,
and adapt treatment at that time. In most patients, response
occurs within 3 months after start of therapy

38. MEMBRANOUS NEPHROPATHY - TREATMENT
Practice Point 3.3.4: Longitudinal monitoring of antiPLA2R antibody levels at 6 months
after start of therapy may be useful for evaluating treatment response in patients
with MN, and can be used to guide adjustments to therapy.

39. MEMBRANOUS NEPHROPATHY - TREATMENT
Practice Point 3.3.4: Longitudinal monitoring of antiPLA2R antibody levels at 6 months
after start of therapy may be useful for evaluating treatment response in patients
with MN, and can be used to guide adjustments to therapy.

40. MEMBRANOUS NEPHROPATHY - TREATMENT
Practice Point 3.3.4: Longitudinal monitoring of antiPLA2R antibody levels at 6 months
after start of therapy may be useful for evaluating treatment response in patients
with MN, and can be used to guide adjustments to therapy.

41. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

42. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.2: Algorithm for management of patients with treatment-resistant MN

43. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.2: Algorithm for management of patients with treatment-resistant MN
In patients with resistant disease,
compliance should be checked and
efficacy monitored (e.g., B-cell response,
anti-rituximab antibodies, IgG levels,
leukocytopenia during
cyclophosphamide, CNI levels).

44. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.2: Algorithm for management of patients with treatment-resistant MN
These centers may choose
experimental therapies
(bortezomib, anti-CD38
therapy, and belimumab) or a
higher dose of conventional
immunosuppressive therapy

45. If proteinuria persists, while serum albumin has increased, one should also consider secondary FSGS. This
would be further supported by the disappearance of anti-PLA2R antibodies.
In patients with persistent proteinuria with normal or near-normal serum albumin levels or patients with
persistent proteinuria despite loss of anti-PLA2R antibodies, a kidney biopsy should be considered to
document active MN.

46. Talk Outline – Membranous Nephropathy
• Presentation
• Diagnosis
• Treatment – anticoagulant prophylaxis
• Treatment – risk stratification
• Treatment – choice of immunosuppressive
• Treatment – resistant cases
• Treatment – relapsing cases

47. MEMBRANOUS NEPHROPATHY – SPECIAL SITUATIONS
Practice Point 3.4.1: Algorithm for the treatment of patients with MN and initial relapse after
therapy