Kidney Flashcards

Question

# Glomerulonephritis by Dr Richard Hull What are podocytes?

Answer 1

**Diseased** actin cytoskeleton derangement loss of slit diaphragm cuboid morphology Limited ability to repair or regenerate **Loss** = glomerulosclerosis

Answer 2

**Descriptive of “minimal changes!”** Normal light microscopy Diffuse foot process effacement on EM **Pattern of injury** Mechanisms unknown Pertubation of T cell biology with the secretion of permeability factors into the circulation Modern focus on dysregulation of podocyte CD89 (B7.1)- lymphocyte CTLA-4 axis **Shows as** Relapsing course with albumin levels and protein:creatinine ratio

Answer 3

Adults – steroids are the first line 53% cured with a single course 13% infrequent relapses 25% frequent relapses 7% progress to end stage - ?actually FSGS Can be secondary – Hodgkin’s, Non-Hodgkin’s, malignant thymoma, renal cell carcinoma, graft versus host disease, drugs e.g. lithium and NSAIDs, light chain disease

Answer 4

It’s a lesion not a specific disease Lots of pathogenetic and aetiologic heterogeneity Primary and viral or drugs – diffuse and generalised foot process effacement Secondary = < 50% of glomerular surface area a histopathologic finding of **scarring** (**sclerosis**) of **glomeruli** and damage to **renal** **podocytes** process damages the filtration function of the kidney, resulting in protein presence in the urine

Answer 5

Minimal Change Disease: Steroids are first-line; relapsing cases may require calcineurin inhibitors. FSGS: Steroids and/or immunosuppressants. Membranous Nephropathy: Immunosuppressants targeting PLA2R antibodies. Vasculitis (ANCA-associated): Immunosuppressants (cyclophosphamide, rituximab). Lupus Nephritis: Mycophenolate mofetil or cyclophosphamide, often with glucocorticoids.

Answer 6

* Most Common Glomerulonephritis: Particularly affects young adults aged 20–30. * Trigger: Often follows a respiratory or gastrointestinal infection, highlighting the role of mucosal surfaces in its pathogenesis. * Pathophysiology: * Mesangial deposition of IgA and complement components (e.g., C3, C5bB, and mannose-binding lectin). * Causes immune complex formation in the glomeruli, leading to inflammation. * Presentation: * Haematuria (visible or non-visible), sometimes with mild proteinuria.

Answer 7

Membranous nephropathy is characterized by immune complex deposition in the glomerular basement membrane (GBM). It is not a single disease but a **pattern** of **injury** that may result from primary (**autoimmune**) or secondary causes. **Presents with nephrotic syndrome:**

Answer 8

Pathogenesis: Caused by **autoantibodies** **targeting** antigens on **podocytes**, including: Phospholipase A2 receptor (PLA2R): Identified in ~80% of cases. Thrombospondin type-1 domain-containing 7A (THSD7A). Results in in situ immune complex formation, complement activation, and podocyte injury.

Answer 9

Associated with **systemic** **conditions**, including: Infections: Hepatitis B, Hepatitis C. Cancer: Solid organ malignancies. Autoimmune Diseases: Lupus nephritis. Drugs: Non-steroidal anti-inflammatory drugs (NSAIDs), gold, penicillamine.

Answer 10

Pauci Immune C3 Deposition Mesangial Immune complex deposits Linear immune complex deposits Subendothelial immune complex deposits Supepithelial immune complex deposits

Answer 11

* Most patients with SLE who develop LN do so within 5 years of an SLE diagnosis * Treatment of LN usually involves immunosuppressive therapy, typically with mycophenolate mofetil or cyclophosphamide and with glucocorticoids, although these treatments are not uniformly effective. * Within 10 years of an initial SLE diagnosis, 5–20% of patients with LN develop end-stage kidney disease ** Patients of black ethnicity v Caucasians** * Develop lupus 2-3 x more * Have onset at a younger age * Develop nephritis more frequently

Answer 12

**Differential has to include small to medium sized vessel vasculitis** IgA Vasculitis Cryoglobulinaemic Vasculitis ANCA-associated vasculitis (AAV) Anti-GBM vasculitis **Diagnosis** History drives differential Immunology to include/exclude including ANA, dsDNA, C3 &C4, Myeloma screen and virology as before ANCA and anti-GBM and consider Cryoglobulins Renal biopsy

Answer 13

* NCA autoantibodies target neutrophil antigens: Proteinase 3 (PR3). and Myeloperoxidase (MPO). These autoantibodies are key drivers of inflammation. * ANCAs bind to neutrophil surfaces, leading to their activation. Activated neutrophils release reactive oxygen species (ROS) and proteolytic enzymes, damaging blood vessels. * Direct injury to small-to-medium-sized vessels, causing necrotizing inflammation. This results in pauci-immune glomerulonephritis (minimal immune complex deposition on histology). * Activated neutrophils and monocytes enhance endothelial injury, perpetuating inflammation. Leads to fibrinoid necrosis and crescentic glomerulonephritis in severe cases.

Kidney Flashcards

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