Glomerular disease

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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 diseases can be classified by their clinical symptoms as below:

Glomerular hematuria:

1- Glomerulonephritis

This disease is further categorized into two pathological patterns named non-proliferative or proliferative types. In each type the treatment options and the clinical outcome are different. These disease spectrum can be due to primary causes or secondary causes (discussed in each type in related chapter separately).

2- Isolated hematuria

For differential diagnosis and causes of isolated hematuria, click here.

Proteinuria:

1- Nephrotic syndrome

2- Isolated proteinuria

For differential diagnosis and causes of isolated proteinuria, click here.

Non Proliferative Glomerulonephritis

This is characterised by a lack of hypercellularity in the glomeruli. They usually cause nephrotic syndrome. This includes the following types:

1. Minimal change GN

This form of GN causes 80% of nephrotic syndrome in children, but only 20% in adults. As the name indicates, there are no changes visible on simple light microscopy, but on electron microscopy there is fusion of podocytes (supportive cells in the glomerulus). Immunohistochemistry staining is negative. Treatment consists of supportive care for the massive fluid accumulation in the patients body (= oedema) and as well as steroids to halt the disease process (e.g. Prednisone 1 mg/ kg). Over 90% of children respond well to steroids, being essentially cured after 3 months of treatment. Adults have a lower response rate (80%). Failure to respond to steroids ('steroid resistant') or return of the disease when steroids are stopped ('steroid dependent') may require cytotoxic therapy (e.g. cyclosporin) which is associated with many side-effects. As we all may know

2. Focal Segmental Glomerulosclerosis (FSGS)

FSGS may be primary or secondary to reflux nephropathy, Alport syndrome, heroin use or HIV. FSGS presents as a nephrotic syndrome with varying degrees of impaired renal function (seen as a rising serum creatinine, hypertension). As the name suggests, only certain foci of glomeruli within the kidney are affected, and then only a segment of an individual glomerulus.

The pathological lesion is sclerosis (fibrosis) within the glomerulus and hyalinisation of the feeding arterioles, but no increase in the number of cells (hence non proliferative). The hyaline is an amorphous material, pink, homogeneous, resulting from combination of plasma proteins, increased mesangial matrix and collagen. Staining for antibodies and complement is essentially negative. Steroids are often tried but not shown to be effective. 50% of people with FSGS continue to have progressive deterioration of kidney function, ending in renal failure.

3. Membranous glomerulonephritis

Presents as nephrotic syndrome, leading cause in adults (35%). It is usually idiopathic, but may be associated with cancers (lung, bowel), infection (hepatitis, malaria), drugs (penicillamine), SLE. The basement membrane on which the glomerular cells sit is thickened, but no increase in cells. Immune staining shows diffuse granular uptake of IgG (immunoglobulin G) and complement type 3. A third of people continue having the disease, 1/3 remit, 1/3 progress to end-stage kidney failure. As glomerulonephritis progresses (in any type), the tubules of the kidney (which are separate to the glomerulus) also become affected, showing atrophy and hyalinisation. The kidney grossly appears shrunken. Treatment with steroids is attempted if it is progressive.

Proliferative Glomerulonephritis

This type is characterised by increased number of cells in the glomerulus (hypercellular). Usually present as a nephritic syndrome and usually progress to end-stage renal failure (ESRF) over weeks to years (depending on type).

1. IgA disease (Berger's nephropathy)

This is the most common type of glomerulonephritis in adults world-wide. It usually presents as macroscopic haematuria (visibly bloody urine). It occasionally presents as a nephrotic syndrome. It often affects young males after an upper respiratory tract infection. Microscopic examination of biopsy specimens shows increased number of mesangial cells with increased matrix (the 'cement' which holds everything together). Immuno-staining is positive for immunoglobulin A deposits within the matrix. Prognosis is variable, 20% progress to ESRF. Steroids and immunosuppression are not effective treatments for this disease; ACE inhibitors are the mainstay of treatment.

2. Post-infectious Glomerulonephritis

Post-infectious glomerulonephritis occurs after Streptococcal infection - usually of the skin, after a latency of 10 days. This condition is essentially defined as an inflammation of the kidneys. Light microscopy shows diffuse hypercellularity due to proliferation of endothelial and mesangial cells, inflammatory infiltrate with neutrophils and with monocytes. The Bowman space is reduced (compressed), in severe cases might see cresent formation [see later]. However, biopsy is seldom done because the disease usually regresses. Patients present with a nephritic syndrome. Diagnosis is suggested by positive streptococcal titers in the blood (ASOT). Treatment is supportive, and the disease resolves (as a rule) in 2 weeks.

3. Mesangiocapillary Glomerulonephritis

This is primary, or secondary to SLE, viral hepatitis, hypocomplementemia. One sees 'hypercellular and hyperlobular' glomeruli due to proliferation of both cells and the matrix within the mesangium. Presents usually with as a nephrotic syndrome but can be nephritic, with inevitable progression to ESRF.

4. Rapidly progressive Glomerulonephritis (Crescentic GN)

As the name suggests, this type has a poor prognosis, with rapid progression to kidney failure over weeks. Any of the above types of GN can be rapidly progressive. Additionally two further causes present as solely RPGN. One is Goodpasture's syndrome. This is an autoimmune disease whereby antibodies are directed against antigens found in the kidney and lungs. As well as kidney failure, patient have hemoptysis (cough up blood). High dose immunosupression is required (intravenous methylprednisone) and cyclophosphamide, plus plasmapharesis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits. The second cause is vasculitic disorders such as Wegener's and polyarteritis. There is a lack of immune deposits on staining, but blood tests are positive for ANCA antibody.

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

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

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  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

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

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

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

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  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.

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

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  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.

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  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.

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

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  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:

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 cryoglobunemia (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 erythmatosus Drugs (NSAIDS, penclliamine, gold, captopril)		+	-	-	-	+/-	-	+	+	-	-	-	+	Thick glomerular basement membrance	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 subepithelial and subendothelial 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 polyngitis	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)	Hemeturia Oliguria Periorbital edema Hypertension	+/-	+	+	+	+	+	-	+	-	-	-	+	Thick glomerular basement membrane (Tram-track appearance)	Mesangial proliferation and leukocyte infiltration	+ (Granular)

References

Related Chapters

• Nephritic syndrome
• Nephritis