Uploaded byNephroTube - Dr.Gawad
Membranous Nephropathy - Management Algorithm - Dr. Gawad
Membranous nephropathy (MN) is a glomerular disease characterized by subepithelial immune deposits causing nephrotic syndrome in many cases. It can be primary or secondary. Evaluation of secondary causes includes screening for autoimmune diseases, viral infections, malignancies and other underlying conditions. Treatment involves treating any identified secondary cause. For primary MN, supportive care is initially recommended, with immunosuppressive therapy considered for persistent high-risk disease. Treatment options include steroids, calcineurin inhibitors and alkylating agents. Close monitoring of response is important to guide management.
In this document
Powered by AI
Introduction to Membranous Nephropathy by Mohammed Abdel Gawad, contact details for further resources.
Overview of Membranous Nephropathy as glomerular disease, nephrotic syndrome prevalence, etiology (primary and secondary causes).
Establishing a biopsy-proven diagnosis and outlining management steps for Membranous Nephropathy.
Exploration of pathological mechanisms leading to subepithelial deposits in Membranous Nephropathy.
Identification and relevance of podocyte antigens (NEP, PLA2R, THSD7A) in Membranous Nephropathy.
Discussion on characteristics, pathogenesis including anti-PLA2R antibody role in idiopathic Membranous Nephropathy.
Evaluating the significance of anti-PLA2R titers in diagnosing and predicting outcomes in Membranous Nephropathy.
Detailed algorithm for diagnosing MN, emphasizing biopsies, age factors, and screening methods.
Guidelines for malignancy screening in patients with Membranous Nephropathy, based on risk factors.
Overview of management steps for Membranous Nephropathy, treatment algorithms, and patient counseling.
Reiteration of key diagnostic and age-related factors significant to the management of Membranous Nephropathy.
Conclusion remarks from Mohammed Abdel Gawad, expressing gratitude.
More Related Content
Similar to Membranous Nephropathy - Management Algorithm - Dr. Gawad
Membranous Nephropathy - Management Algorithm - Dr. Gawad
- 1. Membranous Nephropathy Management Algorithm MohammedAbdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) Alexandria – EGY [email protected] ESNT Outreach Program: Sohag 3-5 Dec 2015
- 2. To download thelecture with full animations please contact me [email protected]
- 3. Membranous Nephropathy • Glomerulardisease: –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.
- 4. Membranous Nephropathy • SubepithelialImmune deposits of IgG and complement Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 5. Membranous Nephropathy • Etiology: Primary (twothird of cases) Secondary Kidney Int Suppl. 2012;2:139-274
- 6. Membranous Nephropathy • Etiology: Secondary KidneyInt Suppl. 2012;2:139-274
- 7. Membranous Nephropathy • Etiology: Secondary KidneyInt Suppl. 2012;2:139-274
- 8. Membranous Nephropathy • Etiology: Secondary KidneyInt Suppl. 2012;2:139-274
- 9. My Starting Point Abiopsy proven diagnosis of Membranous Nephropathy (MN)
- 10. Talk Outline Steps ofManagement of MN (Diagnosis & Treatment) Evaluation of secondary causes Therapy: Secondary: Treat the cause Idiopathic: Specific Treatment Kidney Int Suppl. 2012;2:139-274
- 11. Talk Outline Steps ofManagement of MN (Diagnosis & Treatment) Evaluation of secondary causes Therapy: Secondary: Treat the cause Idiopathic: Specific Treatment Kidney Int Suppl. 2012;2:139-274
- 12. Talk Outline Steps ofManagement of MN (Diagnosis & Treatment) Evaluation of secondary causes Therapy: Secondary: Treat the cause Idiopathic: Specific Treatment To go through evaluation of secondary causes we have to discuss first Clinically applied Pathophysiology of MN Kidney Int Suppl. 2012;2:139-274
- 13. Subepithelial deposits MN PossibleMechanisms 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.
- 14. Subepithelial deposits MN PossibleMechanisms 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. 1ry MN
- 15. Subepithelial deposits MN PossibleMechanisms 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. 1ry MN
- 16. Subepithelial deposits MN PossibleMechanisms 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. 1ry MN
- 17. Subepithelial deposits MN PossibleMechanisms 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. 1ry MN2ry MN 2ry MN
- 18. Subepithelial deposits MN PossibleMechanisms 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. 1ry MN2ry MN 2ry MN
- 19. Animal Model -Heymann nephritis Megalin Quigg RJ. Kidney Int 2003; 64:2318.
- 20. Congenital MN havebeen shown to be mediated by an antibody to neutral endopeptidase (NEP), an antigen expressed on the podocyte membrane. In these cases, mothers with a hereditary absence of NEP become sensitized during pregnancy and passively transfer anti-NEP IgG to the infant, who is born with congenital nephrotic syndrome caused by MN through an alloimmune mechanism Human Podocyte Antigens Neutral Endopeptidase
- 21. Human Podocyte Antigens PhospholipaseA2 Receptor
- 22. Human Podocyte Antigens Thrombospondintype - 1 domain - containing 7A (THSD7A) • A transmembrane protein expressed on podocytes. • Responsible Ab in 10% of idiopathic 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.
- 23. Mechanism of idiopathicMN Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 24. Mechanism of idiopathicMN Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16. Qu Z et al. Nephrol Dial Transplant 27: 1931–1937, 2012
- 25. Mechanism of idiopathicMN Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 26. Mechanism of idiopathicMN Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 27. Mechanism of idiopathicMN Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 28. Mechanism of idiopathicMN Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 29. Characteristics of IdiopathicMN Pathogenesis • Anti PLAR2 Ab. • Th2 Humoral immunity. • IgG4 subclass. • C5b9 (MAC)
- 30. Characteristics of IdiopathicMN Pathogenesis • Anti PLAR2 Ab. • Th2 Humoral immunity. • IgG4 subclass. • C5b9 (MAC)
- 34. Serum PLA2R autoantibodies test is a good +ve but not good -ve marker for MN. Anti-PLA2R Titers Clinical Significance (1)
- 35. Anti-PLA2R Titers ClinicalSignificance (2) • anti-PLA2R titers strongly correlated with clinical status • lower anti-PLA2R titers were associated with a higher rate of spontaneous remission • a decline in anti-PLA2R predicted the clinical response to immunosuppressive therapy Hofstra JM et al. Clin J Am Soc Nephrol 2011; 6:1286. Hofstra JM et al. J Am Soc Nephrol 2012; 23:1735. Ruggenenti P et al. J Am Soc Nephrol 2015; 26:2545.
- 37. Anti-PLA2R Is it onlyrelated to Idiopathic MN? J Am Soc Nephrol 22: 1137–1143, 2011.
- 38. Anti-PLA2R Titers ClinicalSignificance (3) • 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.
- 39. Talk Outline Steps ofManagement of MN (Diagnosis & Treatment) Evaluation of secondary causes Therapy: Secondary: Treat the cause Idiopathic: Specific Treatment Kidney Int Suppl. 2012;2:139-274
- 40. Diagnostic Algorithm Zeng CHet al. Am J Kidney Dis 2008; 52: 691–698. To Exclude Secondary Causes
- 41. 1- Biopsy 1ry MN Subepithelial IgGsubclass 4 Anti PLA2R 2ry MN - Ig other than IgG (e.g. IgA, IgM), particularly in mesangium, subendothelial, tubular BM deposits. - C1q deposits - tubuloreticular structures in the glomerular endothelial cells
- 42. 2- Age 4th to5th decade (suggesting 1ry pathology, but not excluding 2ry causes) - ANA - Anti dsDNA - HBsAg - HCV Ab - Cryoglobulins - RF - C3 - C4 - ESR - CRP If not 4th to 5th decade (suggesting 2ry pathology, but not excluding 1ry causes) Tumor screening: When to screen ? How to screen? Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015.
- 43. 2- Age 4th to5th decade (suggesting 1ry pathology, but not excluding 2ry causes) - ANA - Anti dsDNA - HBsAg - HCV Ab - Cryoglobulins - RF - C3 - C4 - ESR - CRP If not 4th to 5th decade (suggesting 2ry pathology, but not excluding 1ry causes) Tumor screening: When to screen ? How to screen? Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015.
- 44. 2- Age 4th to5th decade (suggesting 1ry pathology, but not excluding 2ry causes) - ANA - Anti dsDNA - HBsAg - HCV Ab - Cryoglobulins - RF - C3 - C4 - ESR - CRP If not 4th to 5th decade (suggesting 2ry pathology, but not excluding 1ry causes) Tumor screening: When to screen ? How to screen? Take care of what is called PURE MEMBERANOUS LUPUS NEPHROPATHY where no clinical or serological evidence of SLE. Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015.
- 45. 2- Age 4th to5th decade (suggesting 1ry pathology, but not excluding 2ry causes) - ANA - Anti dsDNA - HBsAg - HCV Ab - Cryoglobulins - RF - C3 - C4 - ESR - CRP If not 4th to 5th decade (suggesting 2ry pathology, but not excluding 1ry causes) Tumor screening: When to screen ? How to screen? Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015. Serum complement is usually normal in idiopathic MN
- 46. 2- Age 4th to5th decade (suggesting 1ry pathology, but not excluding 2ry causes) - ANA - Anti dsDNA - HBsAg - HCV Ab - Cryoglobulins - RF - C3 - C4 - ESR - CRP If not 4th to 5th decade (suggesting 2ry pathology, but not excluding 1ry causes) Tumor screening: When to screen ? How to screen? Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015.
- 47. Malignancy Screening When toscreen? If the anti-PLA2R antibody test is negative + the kidney histology is consistent with secondary MN + there is no other clear cause of secondary MN + risk factors or alarm signs: • extensive smoking history, • guaiac-positive stools, • unexplained anemia or weight loss Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015.
- 48. Malignancy Screening How toscreen? Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 49. Malignancy Screening How toscreen? Examination: - LN. - Systemic exam for any mass. - CXR - USS Abd & Pelvis - CBC - Occult blood in stool Male > 50 = PSA Female > 50 = Mammogram Body CT Scan (± other imaging) if cause is not evident
- 50. Malignancy Screening Frequency ofscreening 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, Richard J Glassock. UpTodate. Oct 21, 2015.
- 52. Talk Outline Steps ofManagement (Diagnosis & Treatment) Evaluation of secondary causes Therapy: Secondary: Treat the cause Idiopathic: Specific Treatment Kidney Int Suppl. 2012;2:139-274
- 53. Definitions Kidney Int Suppl.2012;2:139-274 Jha V et al. J Am Soc Nephrol 2007; 18:1899–1904. Urinary protein (confirmed by two values at least 1 week apart) Serum albumin S.Cr. Complete Remission - Urinary protein excretion < 0.3 g/d - uPCR < 300 mg/g or < 30 mg/mmol Normal Partial Remission - Urinary protein excretion < 3.5 g/d - uPCR < 3500 mg/g or <350 mg/mmol + 50% or greater reduction from peak values
- 54. Spontaneous complete remission ofproteinuria 5 to 30 % at five years Spontaneous partial remission 25 to 40 % at five years End-stage renal disease in untreated patients 14 % at five years, 35 % at 10 years, 41 % at 15 years Possibility of Remission Jha V et al. J Am Soc Nephrol 2007; 18:1899.
- 55. General Supportive Therapy •Angiotensin inhibition • Lipid lowering • Anticoagulation (if serum albumin <2.5 g/dl and additional risks for thrombosis) • Diuretics to control edema, Salt restriction • Maintenance of adequate nutrition Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015. Claudio Ponticelli, Richard J. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 56. MN - RiskCategories Low Risk Medium Risk High Risk Serum creatinine and creatinine clearance Normal Normal or near-normal Deteriorating renal function Proteinuria <4 g/day 4-8 g/day >8 g/day Supportive treatment period over 6 months of supportive care over 6 months of supportive care over 3-6 months of supportive care Fernando C. Clin J Am Soc Nephrol 3: 905-919, 2008
- 57. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 58. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 59. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 60. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 61. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 62. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 63. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 64. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 65. IMN – TreatmentAlgorithm Kidney Int Suppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 66. The ‘‘Ponticelli Regimen’’ KidneyInt Suppl. 2012;2:139-274
- 67. CNI-based Regimens Kidney IntSuppl. 2012;2:139-274
- 68. Claudio Ponticelli, RichardJ. Glassock. CJASN. 2014 Mar;9(3):609-16.
- 69. Repeat Kidney Biopsy KidneyInt Suppl. 2012;2:139-274
- 72. 1- Biopsy 1ry MN IgGsubclass 4 Anti PLA2R 2ry MN - Ig other than IgG (e.g. IgA, IgM), particularly in mesangium, subendothelial, tubular BM deposits. - C1q deposits - tubuloreticular structures in the glomerular endothelial cells
- 73. 2- Age 4th to5th decade (suggesting 1ry pathology, but not excluding 2ry causes) - ANA - Anti dsDNA - HBsAg - HCV Ab - Cryoglobulins - RF - C3 - C4 - ESR - CRP - Syphilis serology If not 4th to 5th decade (suggesting 2ry pathology, but not excluding 1ry causes) Tumor screening: When to screen ? How to screen? Laurence H Beck, Richard J Glassock. UpTodate. Oct 21, 2015.
- 74. Serum complement isusually normal in idiopathic MN Take care of what is called PURE MEMBERANOUS LUPUS NEPHROPATHY where no clinical or serological evidence of SLE.
- 75. Malignancy Screening How toscreen? Examination: - LN. - Systemic exam for any mass. - CXR - USS Abd & Pelvis - CBC - Occult blood in stool Male > 50 = PSA Female > 50 = Mammogram Body CT Scan (± other imaging) if cause is not evident
- 76. Treatment Algorithm Kidney IntSuppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 77. Treatment Algorithm Kidney IntSuppl. 2012;2:139-274 Hofstra, J. M. et al. Nat. Rev. Nephrol. 9, 443–458 (2013)
- 78.