Glomerulonephritis

David C. Van Metre

Glomerulonephritis (GN) is a rare kidney disorder of ruminants that may result from deposition of antigen-antibody complexes and/or complement in the glomerulus, or from binding of antibody to intrinsic or foreign antigens localized to the glomerulus.

Clinical Signs

Cattle with GN may have a history of lethargy, weight loss, mucous membrane pallor, poor productivity, and chronic diarrhea,^1,2 although the course of disease may be acute in some cases.³ Generalized edema is often apparent, typically involving the brisket and submandibular space. An enlarged but nonpainful left kidney may be felt on rectal palpation.² GN can occur in cattle with liver fluke infestation,⁴ metritis,⁵ or those acutely⁶ or persistently^7,8 infected with bovine viral diarrhea (BVD) virus. As is expected for persistent BVD infec­tion, the appearance of affected cattle can range from unthrifty⁷ to clinically normal.⁸ GN can also occur without a detectable concurrent disease.^2,3 Further, a heritable proliferative glo­merulopathy (defined as hyperplasia of cells within the glomeruli without a marked inflammatory infiltrate) has been described in Gelbvieh calves; clinical signs in affected animals reflect a concurrent peripheral neuropathy that manifests as paraparesis, hind limb ataxia, and recumbency.⁹

In small ruminants, the clinical course of GN is less well described than for cattle, but thin condition, pale mucous membranes, and generalized edema are expected.¹⁰ Subclinical GN has also been detected at necropsy in sheep with caseous lymphadenitis,¹¹ Maedi-Visna virus infection,¹² and in sheep experimentally implanted with long-term, indwelling vascular catheters.¹³ Finnish Landrace lambs may develop GN early in life as a result of a heritable defect in the C3 component of complement.¹⁴ Clinical signs of this disease begin within hours after birth to 3 months of age.

Differential Diagnosis

The differential diagnosis for ruminants with GN is similar to that for amyloidosis (see preceding section).

Clinical Pathology

Heavy proteinuria, mild anemia, hypoalbuminemia, and azote­mia have been reported in ruminants with GN.^1-5,7,10 Variable amounts of granular or hyaline casts, red blood cells, and leukocytes may be found in the urine sediment. GN in Finnish Landrace lambs is characterized by uremia, hypoalbuminemia, proteinuria, hypocalcemia, and hyperphosphatemia.¹⁴

Pathophysiology

In humans and animals, GN may result from a variety of infectious, toxic, or autoimmune disorders, all of which induce eventual immunologic injury to the glomerulus.^15,16 Antibodies may be directed against the host's own antigens or antigens of infectious agents that become “planted” in the vascular endothelium, mesangial cells, or basement membrane. In many cases, circulating immune complexes develop under conditions of sustained antigenemia produced by chronic infections. These immune complexes deposit in the glomeruli and adjacent capillary walls. The ultimate consequences are activation of complement and chemotaxis of leukocytes, both of which result in glomerular injury and increased glomerular permeability.^15,16 Immunohistochemical data suggest involvement of these immune-mediated mechanisms in spontaneous GN,^1-3 as well as GN associated with infection with BVD,^6-8 Maedi-Visna virus,¹² and indwelling vascular catheters.¹³ Notably, glomerular lesions may be found in animals with septicemia, as septic emboli may embed in the glomeruli or surrounding capillary beds, resulting in multifocal glomerulitis.^14-16

Passage of plasma albumin through the damaged glomerulus results in chronic albuminuria, eventually leading to reduced plasma oncotic pressure and generalized edema. Affected animals may develop nephrotic syndrome, characterized by hypoalbu- minemia, generalized edema, unrelenting proteinuria, and hypercholesterolemia^1-3,10; however, because serum cholesterol is not commonly measured in ruminant biochemistry analysis, the frequency of hypercholesterolemia in affected ruminants is unknown.

Treatment and Prognosis

In other species, treatment aimed at removal of the source of antigen in the bloodstream may reduce immune complex deposition and slow or reverse the progression of disease. Treatment of GN in ruminants has not been described. Because most clinically overt cases of GN are advanced at the time of diagnosis in ruminants, the prognosis can be assumed to be poor.