Glomerular Disease 1 (Regner) Flashcards
What are the most common etiologies of glomerular diseases?
By far, idiopathic or immune. This may be deposition of immune complexes, direct antibody action against GBM/glomerular antigens, or chronic inflammation.
What is meant by a “subepithelial” deposition?
Which glomerular disease is this associated with?
In the context of “subepithelial” glomerular deposition, the podocytes act as the “epithelium”, deposition is just beneath them.
Subepithelial deposition is typical of membranous nephropathy (“Spike & Dome”)
Distinguish between the descriptors of diffuse, focal, global and segmental in the context of glomerular disease.
Diffuse/focal refer to the ennumerative glomerular involvement (all or some).
Global/segmental refer to how much of a glomerulus is involved (all or some).
Describe the major and minor signs of nephrotic syndrome.
Major: Proteinuria (>3.5g/day), hypoalbuminemia, edema, hyperlipidemia.
Minor: Lipiduria, hypercoagulability.
Why are edema, hyperlipidemia, and hypercoagulability seen in nephrotic syndromes?
Edema: Loss of albumin & other proteins that contribute to plasma π.
Hyperlipidemia: Response by the liver to the “thinning” of blood.
Hypercoagulability: Loss of proteins C, S; anti-thrombin 3.
Describe the features seen in nephritic syndromes.
Mild proteinuria (<3.5g/day)
Hematuria (often with RBC casts and/or dysmorphic RBCs)
Hypertension
Edema
Which glomerular diseases tend to blur the lines between nephrotic and nephritic pathophysiologies?
Membranoproliferative GN, IgA nephropathy.
IgA Nephropathy
Describe its epidemiology.
What are its clinical features?
What is revealed on histology?
IgA Nephropathy
Most common GN worldwide, usually younger patients.
Prominent hematuria, with dysuria and loin pain, often synpharyngitic. Sometimes subclinical. HTN in severe cases.
Mesangial hypercellularity, granular mesangial IgA deposits.
IgA Nephropathy
How is it treated?
Describe its prognosis.
IgA Nephropathy
Fish oil to slow progression, ACE-I for HTN, steroids/immunosuppressants.
Prognosis is mixed, may slowly develop kidney disease/failure.
What is the pathophysiology of Henoch-Schonlein Purpura?
Describe its clinical presentation.
IgA deposition in multiple organs.
Skin: Non-blanching purpura in lower body.
Joint arthralgias.
GI tract: Pain, vomiting, melena/hematochezia
IgA nephropathy.
Post-Strep Glomerulonephritis
Describe its epidemiology.
What are its clinical features?
What is revealed on histology?
Post-Strep Glomerulonephritis
Typically affects young patients following pharyngeal or skin GAS infection.
Sudden onset hematuria, HTN, oliguria, azotemia and periorbital edema. Labs reveal low C3 and high ASO titers.
Mesangial/endocapillary proliferation with neutrophils. Granular IF deposits in mesangium & subepithelial (“hump-like”)
Post-Strep Glomerulonephritis
How is it treated?
Describe its prognosis.
Post-Strep Glomerulonephritis
Supportive treatment only.
95% of children recover; adults don’t do as well. Small progression to renal failure or RPGN.
What are the classic signs of a Rapidly Progressive Glomerulonephritis?
Renal failure occurring within weeks. Biopsy shows crescents comprised of fibrin and macrophages.
Goodpasture’s Syndrome
Describe its epidemiology.
What are its clinical features?
What is revealed on histology?
Goodpasture’s Syndrome
Mostly affects younger adult men.
Rapidly Progressive GNitis with pulmonary involvement (hemoptysis, pulmonary infiltrates)
Linear IgG/C3 on kidney biopsy IF.
Goodpasture’s Syndrome
Describe its etiology.
Is there always pulmonary involvement?
How is it treated?
Goodpasture’s Syndrome
Antibodies directed against GBM, probably a3 chain of Type IV collagen.
Goodpasture’s implies pulmonary involvement. If not present, this is termed “Anti-GBM disease”
Plasmapheresis, prednisone/cytoxan.
How does a pauci-immune GN present on histology?
What are its causes?
Pauci-immune GNs feature the crescenteric deposits that all RPGNs do, but with no deposition of immun reactants.
Sometimes idiopathic, but may be caused by ANCA vasculites.
How can the ANCA vasculites be distinguished from one another in the context of diagnosing a pauci-immune GNitis?
Wegener’s: cANKA. Granulomas and nasopharyngeal involvement.
Churg-Strauss: pANKA. Granulomas, asthma, eosinophilia.
Microscopic Polyangiitis: pANKA. No granulomas/asthma/eosinophilia.
What are some other signs and symptoms of ANKA vasculites?
Which are specific to Wegener’s granulomatosis?
Alveolar hemorrhage, purpura, mononeuritis multiplex.
Wegener’s: Pulmonary involvement (sinusitis, nasopharyngeal lesions, hemoptysis).
You are suspicious of an RPGN. Histology of a kidney biopsy reveals granular fluorescence, mostly subendothelial, on IF.
What is being stained? What are some possible causes?
Granular fluorescence suggests immune complex deposition.
Causes: Post-strep GN, Lupus (“diffuse proliferative” GN).
Minimal Change Disease
Describe its epidemiology & associations.
What is revealed on histology?
Minimal Change Disease
Most common nephrotic syndrome of children. In adults, associated with NSAIDs, Hodgkin’s lymphoma, and some other neoplasms & infections.
Normal light microscopy and IF (maybe some mesangial IgM). EM reveals podocyte foot effacement.
Minimal Change Disease
How is it treated?
Why might Hodgkin’s lymphoma cause this disease?
Minimal Change Disease
Good response to steroids, though relapses may occur.
Hodgkin’s lymphoma promotes cytokines which contribute to the podocyte effacement.
Membranous Nephropathy
Describe its epidemiology & associations.
What are its clinical features?
What is revealed on histology?
Membranous Nephropathy
Most common nephrotic syndrome of caucasians. Secondary causes include HBV/HCV, SLE, many neoplasms and drugs (eg NSAIDs, penicillamine)
Insidious onset with heavy proteinuria, sometimes HTN, azotemia, and renal vein thrombosis.
Diffuse GBM thickening. Subepithelial granular IgG deposits.
Membranous Nephropathy
Describe its prognosis.
How is it treated?
Membranous Nephropathy
Rule of thirds: 1/3 spontaneous recover, 1/3 are stable, 1/3 have progressive loss.
ACE-I/ARBs, maybe steroids or immunosuppressants.
Focal Segmental Glomerulosclerosis
Describe its epidemiology.
What are its clinical features?
What is revealed on histology?
Focal Segmental Glomerulosclerosis
Most common nephrotic syndrome in Af-Ams.
Aggressive progression; HTN, hematuria, renal failure.
Focal & Segmental Glomerular Sclerosis! Some podocyte effacement. Negative IF (no complex deposition).
