Felipedia

Feline glomerular disease

Glomerular disease is a well-recognized cause of chronic (but not acute) kidney disease in dogs, and is also occasionally observed in cats. Animals with primary glomerular disease as a cause of chronic kidney disease may have somewhat different clinical and laboratory abnormalities than those with primary tubulointerstitial disease. Damage to the glomerular basement membrane results in albuminuria, which may lead to hypoalbuminemia. Animals may then exhibit signs related to hypoalbuminemia (eg, peripheral oedema, hypercoagulability with thrombosis, hypercholesterolemia) instead of or in addition to uraemia.

Secondary glomerulopathies, observed as sequelae of systemic or glomerular hypertension in animals with Stage III or IV chronic kidney disease, are common. Although the overall prevalence of a primary glomerulopathy as an inciting cause is not known, it is apparently more common in dogs than cats.

Immune-mediated glomerulonephropathy is characterized by deposition or in situ formation of immune complexes in the glomerular capillary wall, which then incite inflammatory changes. In one study of dogs, the mean age of presentation for glomerulonephritis was 4-8 yr; 55% were males, and there was no breed predilection. Immune-mediated glomerulonephritis has been associated with neoplasia, rickettsial diseases, systemic lupus erythematosus (SLE), heartworm disease, pyometra, chronic septicaemia, and adenovirus infection, but it is usually idiopathic. Though multifactorial in origin, the glomerular disease associated with hyperadrenocorticism and diabetes mellitus in dogs is rarely attributable to immune complex formation. In one study of cats with glomerulonephritis, the mean age at presentation was 3-4 yr; 75% were males, and there was no breed predisposition. Primary glomerular disease in cats is most frequently associated with chronic infection by feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), or feline infectious peritonitis (FIP) virus but has also been reported in association with neoplasia and systemic inflammatory diseases. The relatively young age and predilection for males reflects the high prevalence of FeLV infection as a cause in reported feline cases.

Amyloid is the name given to any of several chemically inert fibrillar protein subunits that can be deposited in tissue and interfere with normal organ function. All of these proteins are deposited in a β-pleated sheet conformation, which results in the unique appearance and chemical properties of amyloid. Most cases of amyloidosis in dogs and cats, including familial amyloidosis in Shar-Peis and Abyssinian cats, are reactive, or secondary, amyloidosis. In this form of the disease, amyloid A protein is deposited in various tissues after serum levels increase as a result of chronic inflammation. When the kidneys are affected, amyloid deposition in the non-familial forms in dogs usually occurs in the glomerulus. However, in Shar-Peis, at least 25% of Abyssinian cats, and in many domestic cats with the non-familial form of this disease, amyloid is found primarily in the medullary interstitium where it interferes with the renal concentrating mechanism and is more likely to produce non-proteinuric chronic kidney disease than protein-losing glomerular amyloid deposition. Glomerular amyloidosis usually leads to marked proteinuria. The non-familial form of amyloidosis usually affects middle-aged to older dogs and cats. Beagles, Collies, and Walker Hounds are reported to be at increased risk. Animals with the familial form of the disease are usually diagnosed at a younger age.

Clinical Findings

Glomerulopathy often leads to proteinuria (primarily albuminuria) and can produce hypoproteinemia, ascites, dyspnea (due to pleural effusion or pulmonary oedema), and/or peripheral oedema, which may be referred to as the nephrotic syndrome. Protein wasting can produce preferential loss of lean body mass that may be apparent on careful physical examination. Severe or chronic glomerular disease is a cause of chronic kidney disease; most dogs and many cats with glomerular disease eventually develop Stage III or Stage IV disease. Systemic hypertension may be more prevalent in proteinuric chronic kidney disease and may observed at any stage.

Proteinuria may result in loss of antithrombin III through the glomerular basement membrane, leading to a hypercoagulable state in dogs. Proteinuria also contributes to mild thrombocytosis and platelet hypersensitivity, which contribute to coagulation abnormalities in affected dogs, generally when plasma albumin levels are ≤1.0 g/dL. Severe dyspnea secondary to pulmonary thromboembolism or other sequelae of thrombotic disease may be seen in dogs with glomerulonephritis or amyloidosis. It is unclear whether a hypercoagulable state also exists in proteinuric cats, because clinical signs from hypercoagulability have not been reported in cats.

Diagnosis

The serum urea nitrogen, creatinine, and phosphorus concentrations are usually increased, although the degree varies with the stage of chronic kidney disease at the time of diagnosis. Marked proteinuria with oedema may be observed in the presence or absence of azotemia. Physical findings are usually nonspecific except that ascites, pleural effusion, and/or peripheral, pitting, non-painful, subcutaneous oedema, are evident in some animals (75% of cats and 15% of dogs). Although uncommon, urine specific gravity may be inappropriately high for the degree of renal dysfunction. Proteinuria is associated with all forms of glomerular disease, but it must be quantitated to determine whether the protein loss is significant. The urine protein to creatinine ratio is determined in a random urine sample to quantify urinary protein loss; a value >0.5 indicates proteinuria but does not define its origin (glomerular, tubular, or lower tract origin). If the sediment examination eliminates inflammatory urinary tract disease and haemorrhage as the source of proteinuria, then the degree of increase may help distinguish tubular proteinuria (typical ratio value of 0.5-2.5), glomerulonephritis (typical ratio value of 0.5-15), and glomerular amyloidosis (typical ratio value of 0.5-40). However, substantial overlap exists in these ranges, and the ratio will tend to be low in the initial stages of a glomerulopathy, increase in severity as the disease progresses, and then decline terminally as GFR falls to very low levels in late Stage IV disease.

Renal biopsy is often required to determine the type of glomerular disease. Membranous glomerulonephritis is reported most frequently in cats; there is a roughly equal distribution of histologic findings in dogs, with glomerular amyloidosis and membranous, proliferative, and membranoproliferative glomerulonephritis all represented. The degree of proteinuria does not always correlate with the severity of the histologic lesions or the degree of azotemia. Systemic hypertension develops in an unusually large proportion of animals with protein-losing glomerulonephritis; therefore, blood pressure should be determined in all animals with evidence of glomerular disease.

A careful search should be made for an inciting disease process. Abdominal and thoracic radiographs, ultrasonography, and specialized serologic tests can rule out various inflammatory, infectious, and neoplastic diseases. In dogs with glomerulonephritis, this includes tests for SLE (eg, antinuclear antibody titre and LE prep) and appropriate antigen or antibody screening tests for other infectious agents and heartworm disease; in cats, tests for infection with FeLV, FIV, FIP, SLE, and heartworm disease should be included.

Treatment

There are 6 basic principles to therapy in glomerulonephropathies: 1) If a cause of immune-complex disease can be identified, it should be treated. 2) Manifestations of the nephrotic syndrome, if present, should be managed with dietary salt restriction and judicious use of diuretics. 3) Antithrombotics (eg, aspirin) should be considered for hypoalbuminemic (plasma albumin <1.0 g/dL) animals as well as those with low serum levels of antithrombin III (<30% of normal). In dogs with marked proteinuria and serum albumin <2 g/dL, low-dose aspirin therapy is appropriate, unless melena is present or gastric ulceration is suspected. However, aspirin is bound to plasma proteins and is eliminated via the kidneys, so the dosage may need to be adjusted. 4) Because proteinuria may promote interstitial fibrosis, treatment to limit glomerular loss of protein is warranted and may include dietary protein restriction and administration of an ACE inhibitor. 5) Efforts to reduce the magnitude and consequences of glomerular immune complex deposition should be considered, especially in animals with biopsy-confirmed glomerular inflammation and no known primary antigenic stimulus. Immunosuppressive drugs (eg, azathioprine, cyclophosphamide, cyclosporine) can be used in dogs with glomerulonephritis, although results are variable. For amyloidosis, dimethylsulfoxide and colchicine have been tried, but without consistent results. These anti-inflammatory drugs should be administered only on a trial basis with owner consent. Corticosteroids seem to be beneficial only in mild glomerulopathy; they may worsen proteinuria in other glomerulopathies and should be avoided in animals with amyloidosis, as they are reported to enhance amyloid deposition. 6) Manifestations of chronic kidney disease will be observed in accordance with the stage of disease. Appropriate therapy has been discussed elsewhere.

Prognosis

Although one study found that mean survival time of dogs with glomerulonephritis was 87 days, the prognosis with early diagnosis and appropriate therapy is much better. In a recent study of dogs with glomerulonephritis, those receiving a placebo medication survived beyond the entire 6-mo duration of the study. The prognosis for animals with amyloidosis is guarded but variable, with reported mean survival times ranging from 49 days to 20 mo.