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.

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		History and Symtoms									Laboratory Findings		Pathology
												Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
			History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features
Acute Nephritic Syndromes	Poststreptococcal Glomerulonephritis		Streptococcal skin infections Streptococcal pharyngitis 2-3 weeks after infection	Fever Fatigue Skin rash	+/-	+	+/-	+/-	+/-	+/-	+/-	+/-	Anti-DNA antibodies Anti-C1q antibodies Antineutrophil cytoplasmic antibodies (ANCA)	Hypercellular and inflamed glomeruli Sub-epithelial immune complex deposits		Immune complex GN, granular deposit
	Renal disease due to Subacute Bacterial Endocarditis, or cardiac shunt (Atrioventricular)		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
	Lupus Nephritis		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, mostly immune complex GN, granular deposit
	Antiglomerular Basement Membrane Disease (Goodpasture's syndrome)		Young adults	Dry cough Hemoptysis 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		Immune complex GN, Linear deposit
	IgA Nephropathy		Young children History of mucosal infections (e.g. gastroenteritis) and upper respiratory tract infection 2-3 days after infection (synpharyngitic)	Low grade fever Flank pain	+	+/-	+	+/-	+	-	+	-	Immune complex deposition	Crescent formation	Mesangial proliferation	Immune complex GN, granular deposite
	ANCA Small-Vessel Vasculitis	Granulomatosis with Polyangiitis (Wegener's)	Middle age male	Constitutional symptoms Dyspnea Purpura Arthralgias Neurologic dysfunction Sinusitis Otitis media Epistaxis.	+	+	+	+/-	+	-	+	-	ANCA	Necrotizing and crescentic glomerulonephritis	Subendothelial edema Microthrombosis Degranulation of neutrophils	Pauci-immune GN
		Microscopic Polyangiitis	+/-	Constitutional symptoms Dyspnea Purpura Arthralgias Neurologic dysfunction	+	+	+	+	+	+		-	P-ANCA	Hypercellular and inflamed glomeruli (Crescent formation) (pauci-immune)	-	Pauci-immune GN
		Churg-Strauss Syndrome	+/-	Asthma Sinusitis Myalgia  Arthralgia Purpura Arrythmias Peripheral neuropathy	+	+	+	+	+	+		-	C-ANCA	Hypercellular and inflamed glomeruli (Crescent formation)- (pauci-immune)	-	Pauci-immune GN
	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	Immune complex GN, granular deposite
	Henoch-Schönlein purpura		Most common in young male, following upper respiratory infections	Skin manifestations- Palpable purpura on buttocks Gastrointestinal manifestations- Abdominal pain Melena Bloody diarrhea Hematemesis Joints manifestations- Arthralgia	+	+	+	+/-	+	+	-	-		Diffuse mesangial IgA deposits often associated with mesangial hypercellularity		Immune complex GN, granular deposite
	Cryoglobulinemia		Patients having cryoglobulinemia may have positive history of: Hepatitis C infection Hepatitis B infection Leg ulcers Recurrent thrombosis	Pulmonary symptoms: Difficulty breathing Cough Cutaneous symptoms: Purpura  Skin ulcer Gastrointestinal symptoms: Abdominal pain General symptoms: Fever Arthralgia, Myalgia Fatigue Blurring/loss of vision Diplopia Confusion	+/-	+	+/-	+	+/-	+/-	+/-	+/-	+/-	Membranoproliferative glomerulonephritis
Nephrotic Syndrome	Minimal Change Disease		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)		-	+	-	+	+/-	+	-	+		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	Immune complex GN, granular deposite
	Diabetic Nephropathy		For more information on diabetes click here.		-	+	-	+	+/-	+	-	+		Diffuse mesangial matrix expansion (nodular glomerulosclerosis) Increased mesangial hypercellularity Prominent glomerular basement membranes Thick basement membrane without any deposit	Nodular glomerulosclerosis	-
	Glomerular Deposition Diseases	Light Chain Deposition Disease	Occurs in the setting of high tumor burden	-	-	+	-	+	+/-	+	-	+	-	Light-chain deposits	Granular deposits on electron microscopy	Detection of light chain deposits using anti–light chain antibody
		Renal Amyloidosis	For the secondary causes of amloidosis: Tuberculosis Familial Mediterranean fever Rheumatoid arthritis Multiple myeloma	Dyspnea Lethargy Weight loss Bleeding tendency	-	+	-	+	+/-	+	-	+	-	Diffuse glomerular deposition of amorphous hyaline material (nodular pattern), in mesangium (weakly staining with periodic acid-Schiff (PAS)	Nodular deposit	AA amyloidosis type: negative for immunoglobulins and complement AL amyloidosis type: Positive for lambda or kappa light chains
		Fibrillary-Immunotactoid Glomerulopathy	Malignancy Monoclonal gammopathy Autoimmune disease	-	+/-	+	+/-	+/-	+/-	+	+/-	+/-	-	Diffuse sclerosing glomerulonephritis Diffuse proliferative glomerulonephritis Membranoproliferative glomerulonephritis Mesangioproliferative/sclerosing disease Membranous glomerulonephritis	Large fibrillar deposits in the mesangium randomly Glomerular capillary walls different from amloidosis No staining with Congo red or thioflavine-T or with antibodies to a specific type	Positive for immunoglobulin G (IgG), C3 Kappa and lambda (ie, polyclonal) light chains
		Fabry's Disease	Family history suggestive of the disorder	Anhidrosis or decreased sweating Fatigue Angiokeratomas Burning pain of the extremities Corneal opacities. Dysphagia Abdominal pain Steatorrhea Chest pain and palpitations Delayed puberty Raynaud's phenomenon Hearing loss Telangiectasis Ataxia	-	+	-	+	+/-	+	-	+	-	Vacuolization of visceral glomerular epithelial cells (podocytes) and distal tubular epithelial cells Glycolipid accumulation	Myeloid or zebra bodies: Gb3 deposition within enlarged secondary lysosomes as lamellated membrane structures Inclusions, composed of concentric layers (onion skin appearance)	-
Basement Membrane Syndrome	Alport's Syndrome		Positive family history	Auditary: Early Tinnitus Vertigo High-frequency progressive bilateral hearing loss Occular problems: Refractory Error Arcus Glaucoma Vogt’s White Limbal Girdle Band Keratopathy Lenticonus Spherophakia Cataracts Lens Coloboma Anterior Lenticonus Flecked Retinopathy of the Macula or Periphery	-	+	-	+	+/-	+	-	+	-	Early stage: unremarkable Late stages: glomerulosclerosis, interstitial fibrosis, and interstitial foam cells (due to prolonged proteinuria).	Within glomerular basement membrane (GBM): longitudinal splitting of the lamina densa	Absence of staining of the alpha-3, alpha-4, and alpha-5 (IV) chains in the glomerular basement membrane Minimal binding to a glomerulus in indirect immunofluorescence microscopy with anti-glomerular basement membrane antibodies
	Thin Basement Membrane Disease		Positive family history Gross hematuria following upper respiratory tract infection	-	-	+	-/+	-	-/+	-	-/+	-	-	-	Diffuse thinning of the glomerular basement membranes (GBM)	-
	Nail-Patella Syndrome		Positive family history	Poorly developed fingernails, toenails, and patellae (kneecaps). Elbow deformities Abnormally shaped pelvis bone (hip bone) Knee may be small, deformed or absent	+	+	-	-	-	-	-	-	-	Mostly unremarkable changes Secondary FSGS Late stages: Global glomerulosclerosis, Tubulointerstitial fibrosis	Glomerular basement membranes (GBMs): Focal or diffuse irregular thickening with electron-lucent areas (moth-eaten appearance) containing type III collagen bundles. Similar collagen fibrils can be seen in mesangial matrix. Podocytes: Segmental effacement of foot processes.	Immunofluorescence studies are typically negative. Nonspecific IgM and C3 deposition may be seen in sclerotic glomeruli.
Glomerular-Vascular Syndromes	Hypertensive Nephrosclerosis		Chronic hypertension	Hypertensive retinal changes. high jugular venous pressure Rales from pulmonary edema on auscultation .Signs of left ventricular hypertrophy Left ventricular heave Shifting of apex towards the left S3 and gallop rhythm Loud S2 Ascites Paralysis from stroke secondary to hypertension Inferior limb edema	+/-	+/-	+	+/-	+/-	+/-	-	+/-	-	Interstitial fibrosis and atrophy Medial thickening and intimal fibrosis of medium-sized and larger vessels Arteriolar thickening, and hyalinosis Chronic stages: Global sclerosis Focal segmental sclerosis
	Cholesterol Emboli		Atherosclerotic cardiovascular disease Anticoagulation therapy Cardiopulmonary resuscitation Hypertension Aortic aneurysm Hypercholesterolemia Smoking history Male sex Age over 55 years Vascular procedures Invasive angiography Aortic aneurysm rupture or surgery Vascular surgery	Depends on the organ involved	+/-	+/-	+	+/-	+/-	+/-	-	+/-	-	Atheroemboli are seen in interlobular and arcuate arteries, as lance-shaped clefts, due to dissolution of cholesterol crystals Acute lesions: Atheroemboli are surrounded by red blood cells, fibrin, and leukocytes, with multinucleated giant cell reactions Chronic lesions: Cholesterol clefts are surrounded by intimal fibrosis Vessel recanalization of chronic lesions can occur. Global and segmental sclerosis of glomeruli may be present.	Extensive foot process effacement can be seen	Not specific changes
	Sickle Cell Disease		Positive family history	Pain and/or bone pain Dactylitis Blurry vision Persistent and painful erection Numbness Tingling Motor skill loss Speech deficits Gait disturbance Leg ulceration Jaundice	+/-	+/-	+/-	-	-	-	-	-	-	Glomerular hypertrophy Hemosiderin deposits Focal areas of hemorrhage or necrosis Chronic stage: interstitial inflammation, edema, fibrosis, tubular atrophy, and papillary infarcts Glomerular enlargement and focal segmental glomerulosclerosis (FSGS)
	Thrombotic Microangiopathies		Click for more information on Thrombotic Microangiopathies.		+	+/-	+	+/-	+/-	+/-	-	-	-	Acute stage: Inravasculr fibrin thrombi Chronic stage: Endocapillary hypercellularity. Intimal proliferation of arterioles	Swollen glomerular endothelial cells with loss of fenestrations Chronic stage: interposed cells with new GBM matrix material deposition.	Thrombi stain positive for fibrinogen
	Antiphospholipid Antibody Syndrome		Thrombosis Miscarriage  History of nephropathy History of hematologic abnormalities Nonthrombotic neurologic symptoms, such as migraine headaches Pulmonary hypertension	Fatigue Fever Weight loss Venous thrombosis Arterial thrombosis Thrombocytopenia Recurrent fetal loss	+	+/-	+	+/-	+/-	+/-	-	-	-	Acute stage: Inravasculr fibrin thrombi Chronic stage: Endocapillary hypercellularity. Intimal proliferation of arterioles	Swollen glomerular endothelial cells with loss of fenestrations Chronic stage: interposed cells with new GBM matrix material deposition.	Thrombi stain positive for fibrinogen

Some infectious diseases such as HIV, HBV, HCV, syphilis, leprosy, malaria, and schistosomiasis may cause glomerular diseases.

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.

• 

  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.

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:

• Crescentic GN

• Chronic GN

References

Related Chapters

• Nephritic syndrome
• Nephritis