Glomerular disease

This page contains general information about Glomerular disease. For more information on specific types, please visit the pages on nephritic syndromes, nephrotic syndrome, Fabry's Disease, Amyloidosis, Pulmonary-Renal Syndromes (vasculitis), Thin Basement Membrane Disease, Alport's Syndrome, Anti-GBM Disease, Hypertensive Nephrosclerosis, and Subacute Bacterial Endocarditis.

Glomerular disease
Acute Glomerulonephritis: Micro H&E high mag; an excellent example of acute exudative glomerulonephritis. Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

Glomerular disease Main page
Glomerular disease patient information
Overview
Classification 1- Poststreptococcal Glomerulonephritis 2- Renal disease due to Subacute Bacterial Endocarditis, or cardiac shunt 3- Lupus nephritis 4- Goodpasture syndrome 5- IgA nephropathy 6- Granulomatosis with Polyangiitis (Wegener's) 7- Microscopic Polyangiitis 8- Churg-Strauss Syndrome 9- Membranoproliferative Glomerulonephritis 10- Henoch-Schönlein purpura 11- Cryoglobulinemia 12- Minimal change disease 13- Focal segmental glomerulosclerosis 14- Membranous glomerulonephritis 15- Diabetic Nephropathy 16- Glomerular deposition disease 17- Alport's Syndrome 18- Thin Basement Membrane Disease 19- Nail-Patella Syndrome 20- Hypertensive nephrosclerosis 21- Cholesterol Emboli 22- Sickle Cell Disease 23- Thrombotic Microangiopathies 24- Antiphospholipid Antibody Syndrome
Pathophysiology
Differential Diagnosis
Diagnosis
Prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2], Syed Hassan A. Kazmi BSc, MD [3]

Overview

Glomerular disease is a condition that affects the glomerulus. It consists of different diseases with different clinical courses and treatment options. Glomerular disease can be isolated hematuria, isolated proteinuria; acute or chronic glomerulonephritis, and nephrotic or nephritic features of glomerulonephritis. The end stage of all of these diseases will be glomerulosclerosi swhich is characterized by fibrosis of the glomerulus, and end-stage renal disease.

Classification

Glomerular dieseases can be classified into several clinical and pathological syndromes as below:

Syndrome	Disease
Acute nephritic syndromes	Poststreptococcal Glomerulonephritis Subacute Bacterial Endocarditis Lupus Nephritis Antiglomerular Basement Membrane Disease IgA Nephropathy ANCA Small-Vessel Vasculitis Granulomatosis with Polyangiitis (Wegener's) Microscopic Polyangiitis Churg-Strauss Syndrome Membranoproliferative Glomerulonephritis Mesangioproliferative Glomerulonephritis
Nephrotic syndrome	Minimal Change Disease Focal Segmental Glomerulosclerosis Membranous Glomerulonephritis Diabetic Nephropathy
Glomerular Deposition Diseases	Light Chain Deposition Disease Renal Amyloidosis Fibrillary-Immunotactoid Glomerulopathy Fabry's Disease
Pulmonary-Renal Syndromes:	Goodpasture's syndrome granulomatosis with polyangiitis (Wegener's) microscopic polyangiitis Churg-Strauss vasculitis Henoch-Schönlein purpura cryoglobulinemia
Basement Membrane Syndromes	Anti-GBM Disease Alport's Syndrome Thin Basement Membrane Disease Nail-Patella Syndrome
Glomerular-Vascular Syndromes	Atherosclerotic Nephropathy Hypertensive Nephrosclerosis Cholesterol Emboli Sickle Cell Disease Thrombotic Microangiopathies Antiphospholipid Antibody Syndrome
Infectious Disease–Associated Syndromes	Post-Streptococcal Glomerulonephritis Subacute Bacterial Endocarditis Human Immunodeficiency Virus Hepatitis B and C Other Viruses Syphilis Leprosy Malaria Schistosomiasis Other Parasites

Glomerular diseases also may classified by their presentation as below:

Glomerular hematuria:

1- Isolated hematuria

2- Glomerulonephritis (nephritic syndrome)

Proteinuria:

1-Isolated non-nephrotic proteinuria 

2- Nephrotic syndrome

Rapidly progressive glomerulonephritis

Glomerulonephritis

Glomerulonephritis which is inflammation of the glomeruli can be classified based on pathogenic type into three subtypes:

• Immune complex glomerulonephritis: Granular deposit of immune complex.
  1. Infection mediated types
  2. Autoimmune types, eg SLE
  3. MPGN
  4. IgA nephropathy (Berger nephropathy)
  5. Membranous nephropathy

• Anti-GBM disease: Linear deposit
  1. Goodpasture syndrome (renal and lung involvement)
  2. Renal involvement alone
  3. Lung involvement alone

• ANCA associated, small vessels vasculitis: Few or no deposit
  1. Granulomatosis with polyangiitis (Wegener granulomatosis)
  2. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
  3. Microscopic polyangiitis

Glomerulonephritis (nephritic syndrome) also may be classified based on disease course into acute or chronic nephritic syndrome; primary vs secondary causes; or systemic vs renal limited disease. For more information about nephritic syndrome classifications click here.

Pathophysiology

Microscopic Pathology

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 

  Glomerulonephritis: Micro H&E med mag; an excellent example of AGN with many neutrophils

• 

  Acute Glomerulonephritis: Micro H&E high mag; an excellent example of acute exudative glomerulonephritis.

Glomerulonephritis Videos

Rapidly progressive glomerulonephritis

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Chronic glomerulonephritis

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Images

Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 

  This is a low-power photomicrograph of a saggital section of end stage chronic glomerulonephritis (GN). Note the marked thinning of the cortex (arrow).

• 

  This is a higher-power photomicrograph of hyalinized glomeruli (arrows) and glomeruli with thick basement membranes.

• 

  This is a higher-power photomicrograph of hyalinized glomeruli (1) and glomeruli with thickened basement membranes (2).

• 

  This is a photomicrograph of interstitial and vascular lesions in end stage renal disease.

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  This is an immunofluorescent photomicrograph of granular membranous immunofluorescence (immune complex disease). The antibody used for these studies was specific for IgG.

• 

  This is an electron micrograph of subepithelial granular electron dense deposits (arrows) which correspond to the granular immunofluorescence seen in the previous image.

• 

  This is a photomicrograph of a glomerulus from another case with acute poststreptococcal glomerulonephritis. In this case the immune complex glomerular disease is ongoing with necrosis and accumulation of neutrophils in the glomerulus.

• 

  This immunofluorescent photomicrograph of a glomerulus from a case of acute poststreptococcal glomerulonephritis shows a granular immunofluorescence pattern consistent with immune complex disease. The primary antibody used for this staining was specific for IgG; however antibodies for complement would show a similar pattern.

• 

  This electron micrograph demonstrates scattered subepithelial dense deposits (arrows) and a polymorphonuclear leukocyte in the lumen.

• 

  For comparison this is an immunofluorescent photomicrograph of a glomerulus from a patient with Goodpasture's syndrome. The linear (arrows) immunofluorescence is characteristic of Goodpasture's syndrome.

Images:

• Crescentic GN

• Chronic GN

Differential Diagnosis

Glomerular diseases	Sub-entity		Causes and associations	History and Symtoms							Laboratory Findings
											Hyperlipidemia and hypercholesterolemia	Nephrotic features	Nephritic features	ANCA	Anti-glomerular basement membrane antibody (Anti-GBM antibody)	Immune complex formation	Light microscope	Electron microscope	Immunoflourescence pattern
				History	Pitting edema	Hemeturia (pre-dominantly microscopic)	Hypertension	Hemoptysis	Oliguria	Peri-orbital edema
Acute Nephritic Syndromes	Poststreptococcal Glomerulonephritis
	Subacute Bacterial Endocarditis
	Lupus Nephritis
	Antiglomerular Basement Membrane Disease
	IgA Nephropathy
	ANCA Small-Vessel Vasculitis	Granulomatosis with Polyangiitis (Wegener's)
		Microscopic Polyangiitis
		Churg-Strauss Syndrome
	Membranoproliferative Glomerulonephritis
	Mesangioproliferative Glomerulonephritis
Nephrotic Syndrome	Minimal Change Disease
	Focal Segmental Glomerulosclerosis
	Membranous Glomerulonephritis
	Diabetic Nephropathy
Glomerular Deposition Diseases	Light Chain Deposition Disease
	Renal Amyloidosis
	Fibrillary-Immunotactoid Glomerulopathy
	Fabry's Disease
Pulmonary-Renal Syndromes:	Goodpasture's syndrome
	granulomatosis with polyangiitis (Wegener's)
	microscopic polyangiitis
	Churg-Strauss vasculitis
	Henoch-Schönlein purpura
	cryoglobulinemia
Basement Membrane Syndromes	Anti-GBM Disease
	Alport's Syndrome
	Thin Basement Membrane Disease
	Nail-Patella Syndrome
Glomerular-Vascular Syndromes	Atherosclerotic Nephropathy
	Hypertensive Nephrosclerosis
	Cholesterol Emboli
	Sickle Cell Disease
	Thrombotic Microangiopathies
	Antiphospholipid Antibody Syndrome
Infectious Disease–Associated Syndromes	Post-Streptococcal Glomerulonephritis
	Subacute Bacterial Endocarditis
	Human Immunodeficiency Virus
	Hepatitis B and C
	Other Viruses
	Syphilis
	Leprosy
	Malaria
	Schistosomiasis
	Other Parasites

Glomerulonephritis may be proliferative or non-proliferative and may be associated with nephrotic or nephritic features. The various types of glomerulonephritides should be differentiated from each other based on associations, presence of pitting edema, hemeturia, hypertension, hemoptysis, oliguria, peri-orbital edema, hyperlipidemia, type of antibodies, light and electron microscopic features. The following table differentiates between various types of glomerulonephritides:

Glomerulonephritis	Sub-entity	Causes and associations	History and Symtoms							Laboratory Findings
										Hyperlipidemia and hypercholesterolemia	Nephrotic features	Nephritic features	ANCA	Anti-glomerular basement membrane antibody (Anti-GBM antibody)	Immune complex formation	Light microscope	Electron microscope	Immunoflourescence pattern
			History	Pitting edema	Hemeturia (pre-dominantly microscopic)	Hypertension	Hemoptysis	Oliguria	Peri-orbital edema
Non-proliferative	Minimal change disease	Idiopathic Protein tyrosine phosphatase receptor type O (glomerular epithelial protein 1- GLEPP1)	Young children Recent infection and immunization Atopy Hodgkin lymphoma Thrombosis (due to urinary loss of antithrombin-III)	+	-	-	-	+/-	-	+	+	-	-	-	-	Normal	Fusion of podocytes	-
	Focal segmental glomerulosclerosis	Idiopathic HIV Heroine use Sickle cell disease Interferon Severe obesity Mixed cryoglobulinemia (Hepatitis C)	Adults	+	-	-	-	+/-	-	+	+	-	-	-	-	Focal (some glomeruli) and segmental (only part of glomerulus)	Effacement of podocytes	-
	Membranous glomerulonephritis	Idiopathic Hepatitis B and C Solid tumors Systemic lupus erythematosus Drugs (NSAIDS, pencilamine, gold, captopril)		+	-	-	-	+/-	-	+	+	-	-	-	+	Thick glomerular basement membrane	Sub-epithelial immune complex depositis with 'spike and dome' appearance	-
Proliferative	IgA nephropathy	Idiopathic Viral infections	Young children History of mucosal infections (e.g. gastroenteritis) and upper respiratory tract infection 2-3 days after infection (synpharyngitic)	+/-	+	+	-	+	+/-	-	-	+	-	-	+	Crescent formation	Mesangial proliferation	-
	Rapidly progressive glomerulonephritis	Goodpasture syndrome	Young adults	+/-	+	+	+	+	+	-	-	+	-	+	+	Hypercellular and inflamed glomeruli (Crescent formation)	Diffuse thickening of the glomerular basement membrane with absence of sub-epithelial and sub-endothelial deposits	+ (Linear)
		Post infectious glomerulonephritis	Streptococcal skin infections Streptococcal pharyngitis 2-3 weeks after infection	+/-	+	+	+	+	+	-	-	+	-	-	+	Hypercellular and inflamed glomeruli	Sub-epithelial immune complex deposits	+ (Granular)
		Granulomatosis with polyangitis (Wegner's granulomatosis)	Necrotizing granulomas (Nasopharynx, lungs, kidneys) Conjunctivitis Ulceration of the cornea Episcleritis Peripheral neuropathy	+/-	+	+	+	+	+	-	-	+	+ (C-ANCA)	-	-	Hypercellular and inflamed glomeruli (Crescent formation)	- (pauci-immune)	+/-
		Churg Strauss syndrome	Necrotizing granulomas (Lungs and kidneys) Asthma Peripheral neuropathy	+/-	+	+	+	+	+	-	-	+	+ (C-ANCA)	-	-	Hypercellular and inflamed glomeruli (Crescent formation)	- (pauci-immune)	-
		Microscopic polyangiitis	Necrotizing vasculitis (no granuloma)	+/-	+	+	+	+	+	-	-	+	+ (P-ANCA)	-	-	Hypercellular and inflamed glomeruli (Crescent formation)	- (pauci-immune)	-
	Membranoproliferative glomerulonephritis	Idiopathic Hepatitis B and C (Type 1) C3 nepritic factor (Type2)	Hematuria Oliguria Periorbital edema Hypertension	+/-	+	+	+	+	+	-	+	-	-	-	+	Thick glomerular basement membrane (Tram-track appearance)	Mesangial proliferation and leukocyte infiltration	+ (Granular)

References

Related Chapters

• Nephritic syndrome
• Nephritis