Glomerulonephropathies

Immune complex-mediated (ICGN)

Introduction:

Immune complex-mediated glomerulonephritis (ICGN) occurs in conjunction with persistent infections or other diseases with prolonged antigenic stimulation.  The potential causes include neoplasia, viral, bacterial, autoimmune, Rickettsia, Helmenthic, and protozoal. In many cases, the exact cause of the ICG is unknown. ICGN occurs most commonly in dogs and cats.

Pathophysiology:

It is a type III hypersensitivity reaction initiated by the formation of soluble antigen-antibody complexes that are deposited in the gomerular capillaries, stimulating complement fixation with the formation of C3a, C5a, and other complexes that are chemotaxic to neurotrophils. The responding neutrophils infiltrate the kidney and damage the basement membrane of the glomerulus; monocytes responding later further damage the glomeruli.  In addition, platelet aggregation, activation of the coagulation system and fibrin deposition add to the glomerular inflammation.

The glomerulus responds to the damage by cellular proliferation, thickening of the glomerular basement membrane, and eventual sclerosis. Once a glomerulus or tubule has been irreversibly damaged, the entire nephron can no longer function. As more nephrons are injured, the glomerular filtration decreases. The remaining functional nephrons then overcompensate and the increased glomerular filtration rates may cause further damage. Extensive damage causes fibrosis and eventual glomerulosclerosis.

The amount of antigen-antibody complex, the length of time of the underlying disease process, the relative permeability of the vascular walls, and the size and molecular weight of the complexes are important factors determining the severity of the ICG. The smaller complexes are the most damaging since the larger complexes are removed from the circulation through phagocytosis by the mononuclear-phagocyte system in the liver and spleen.

Gross Pathology:

Gross lesions of acute ICG are usually subtle. The kidneys are swollen, with a smooth capsule, with normal color or pale. In chronic cases, the kidney becomes shrunken with a generalized finely granular capsular surface. With disease progression, intensive scarring develops throughout the cortex.

Histopathology:

Microscopically, the lesions of ICG may be of three different forms: proliferative, membranous, or membranoproliferative. Proliferative form occurs due to an increased cellularity in the glomerular tufts due to proliferation of the glomerular cells. Membranous form is due to diffuse thickening of the capillary basement membrane; it is the most common form in cats. Membranoproliferative form is most commonly found in dogs; it is the form that occurs with both hypercellularity and basement membrane thickening.              http://www.vetmed.wsu.edu/medsci520/inflamm.htm              WSU/UI Medical Science 520              Robert Wilson, PhD, DVM

Diagnosis:

A renal biopsy is used for diagnosis of ICGN.   The presence of IgG and C3 on glomerular tufts under immunofluorescent or immunohistochemical techniques is a positive diagnosis. Once the diagnosis of ICG is made, the specific causative antigen is usually not known.            http://www.vetmed.wsu.edu/medsci520/inflamm.htm              WSU/UI Medical Science 520              Robert Wilson, PhD, DVM

It is very important to differentiate ICG from other glomerulonephropathies, such as amyloidosis, due to the different prognosis. ICG is due to a type III hypersensitivity reaction and can be treated to lessen the clinic signs. Amyloidosis is an irreversible cause of chronic renal failure.
 

Clinical signs:

The nephrotic syndrome is usually the first sign of disease, and then followed by chronic renal failure. Other signs related to renal failure, such as oral ulceration, vomiting, dehydration, and emaciation, may be seen. Other  signs may be present related to the primary inflammatory or neoplastic process.

For more information:

Carlton, W.W., and McGavin, M.D. 1995. Immune complex mediated glomerulonephritis. Chapter 5: The Urinary System. In: Thompson's Special Veterinary Pathology. Mosby pp 226-229.

Grauser, G.F., and DiBartola, S.P.  Immune complex glomerulonephritis. Chapter 170:Glomerular disease. In: Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat, 5th edition. 2000.Ettinger and Feldman.

Pubmed:

immune complex glomerulonephritis in dogs

immune complex glomerulonephritis in cats