Glomerular disease

This page contains general information about Glomerular disease. For more information on specific types, please visit the pages on nephritic syndrome, 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

Also, glomerular diseases can be classified based on their clinical and urinary pattern in to below types:

Mild nephritc:

This category include mild nephritic sediment that is associated with less than half involvement of glomeruli.

Severe nephritic:

More severe clinical features such as edema, heavy proteinuria, hypertension, and/or renal failure may occur.

Nephrotic:

This syndrome is associated with heavy proteinuria and lipiduria.

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

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:

Glomerular diseases	Sub-entity		Causes and associations	History and Symtoms						Laboratory Findings				Pathology			Comments
										Hyperlipidemia and hypercholesterolemia	Nephrotic features	Nephritic features	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
				History	Systemic syptoms	Pitting edema	Hemeturia (pre-dominantly microscopic)	Hypertension	Oliguria
Acute Nephritic Syndromes	Poststreptococcal Glomerulonephritis		Post infectios: group A beta-hemolytic streptococcus	History of prior skin or throat streptococcal infection	Fever Fatigue Skin rash	+/-	+/-	+/-	+/-	+/-	+/-	+/-	Anti-DNA antibodies Anti-C1q antibodies Antineutrophil cytoplasmic antibodies (ANCA)	Diffuse proliferative glomerulonephritis Prominent endocapillary proliferation Neutrophils  Small subepithelial hump-shaped deposits			Pathologic involvement correlates with the clinical findings
	Renal disease due to Subacute Bacterial Endocarditis, or cardiac shunt (Atrioventricular)		Systemic immune reaction to bacterial endocarditis	History of infective endocarditis mostly due to S. aureus Cardiac shunt	Fever Fatigue Weight loss	+/-	+/-	+/-	+/-	+/-	+/-	+/-	ANCA (myeloperoxidase) positive in 1/3 Activation of the alternative complement pathway (Decreased C3, C4) Positive RF Positive anti-GBM autoantibodies	Crescentic GN is the most common pathological features Diffuse membranoproliferative glomerulonephritis features Focal proliferative GN Mesangial proliferative GN	Mesangial deposits, Subendothelial deposits Subepithelial "humps," in minority of cases	Pauci-immune GN by immunofluorescence
	Lupus Nephritis		SLE risk factors	History of SLE features	Lupus criteria: Malar rash Arthritis Arthralgia Anemia Easy bruising	+/-	+/-	+/-	+/-	+/-	+/-	+/-	Anti-C1q antibodies Anti-dsDNA	Differs based on the disease classification	Differs based on the disease classification	Differs based on the disease classification	Disease presentation is different based on lupus nephritis classifications
	Antiglomerular Basement Membrane Disease (Goodpasture's syndrome)		Young adults	+/-	Dry cough Hemoptesis Malaise  Fever and chills Arthralgia  Fatigue Lethargy Pallor Anorexia Easy bruising	+	+	+	+	-	+	-	ANCA (myeloperoxidase) Positive anti-GBM autoantibodies	Hypercellular and inflamed glomeruli (Crescent formation)  Diffuse thickening of the glomerular basement membrane with absence of sub-epithelial and sub-endothelial deposits	+ (Linear)
	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)		+/-	+	+	+	-	-	+	Immune complex deposition	Crescent formation	Mesangial proliferation	-
	ANCA Small-Vessel Vasculitis	Granulomatosis with Polyangiitis (Wegener's)			Constitutional symptoms Dysnea Purpura Arthralgias Neurologic dysfunction								ANCA
		Microscopic Polyangiitis	Necrotizing vasculitis (no granuloma)	+/-		+	+	+	+	-	+	+ (P-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)	-
		Renal-limited vasculitis (RLV)
	Membranoproliferative Glomerulonephritis		Idiopathic Hepatitis B and C (Type 1) C3 nepritic factor (Type2)	Hematuria Oliguria Periorbital edema Hypertension		+/-	+	+	+	-	+	-	Immune complex deposition	Thick glomerular basement membrane (Tram-track appearance)	Mesangial proliferation and leukocyte infiltration	+ (Granular)
	Mesangioproliferative Glomerulonephritis
	Henoch-Schönlein purpura
	Cryoglobulinemia
Nephrotic Syndrome	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)			+	-	-	+/-	+	+	-	Immune complex deposition	Thick glomerular basement membrane	Sub-epithelial immune complex depositis with 'spike and dome' appearance	-
	Diabetic Nephropathy
Glomerular Deposition Diseases	Light Chain Deposition Disease
	Renal Amyloidosis
	Fibrillary-Immunotactoid Glomerulopathy
	Fabry's Disease
Basement Membrane Syndrome	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		Streptococcal skin infections Streptococcal pharyngitis 2-3 weeks after infection	+/-		+	+	+	+	-	+	-		Hypercellular and inflamed glomeruli Sub-epithelial immune complex deposits	+ (Granular)
	Subacute Bacterial Endocarditis
	Human Immunodeficiency Virus
	Hepatitis B and C
	Other Viruses
	Syphilis
	Leprosy
	Malaria
	Schistosomiasis
	Other Parasites

References

Related Chapters

• Nephritic syndrome
• Nephritis