Proteinuria, significant and persistent, with a non-inflammatory urine sediment is the hallmark of GN. Hematuria and pyuria will interfere with accurate assessment by contributing to the protein measured. In dilute urine, even a trace of protein can be significant. Azotemia and isosthenuria may not be seen in the early course of the disease. This reinforces the importance of a urinalysis in evaluating canine and feline patients.

Urine protein:creatinine (P:C) ratio is used to quantitate the magnitude of urine protein loss. A P:C ratio > 0.8 is abnormal in dogs, and > 0.7 is abnormal in cats, although GN is usually associated with ratios of 3.5 or greater.

Hypoalbuminemia occurs in many dogs and cats with GN. For example, albumin levels < 2.1 gm/dL were found in 70% of dogs with amyloidosis and 32% of dogs with GN. Other laboratory findings in dogs and cats with renal failure caused by GN include nonregenerative anemia, lymphopenia, azotemia, hyperphosphatemia, hypercholes-terolemia, hypoalbuminemia, mild hyperglycemia (caused by insulin resistance), and metabolic acidosis. When present, azotemia reflects prerenal (dehydration) and/or renal (> 75% loss of nephrons) factors. Isosthenuria reflects solute diuresis or concurrent renal tubular dysfunction. Hyaline and granular casts may also be present in the urine sediment.

Medical work-up includes a CBC, chemistry panel, urinalysis, urine P:C ratio, urine culture, blood pressure measurement, abdominal radiographs and ultrasound. Identification of an underlying primary problem needs to be pursued. Definitive diagnosis of GN requires renal biopsy. Performing renal biopsies can result in further deterioration of renal function, and so pros and cons of performing the procedure need to be carefully considered. A coagulation profile and bleeding time should be performed prior to biopsy.

Successful treatment/management in GN patients depends on identifying an underlying etiology (if possible), correcting the problem, and medical management.

Medical management of GN may include immunosuppressive therapy (cyclophosphamide, azathioprine, chlorambucil or cyclosporine); anti-inflammatory-hypercoagulability treatment (aspirin); dietary control (sodium restriction); anti-hypertensive medication (enalapril, amlopidine), and diuretics. Ideally, renal biopsies should be obtained before instituting immunosuppressive therapy. One controlled study assessed the effects of cyclosporine treatment in dogs with idiopathic GN, but was found to have no benefit in reducing proteinuria.

Use of corticosteroids is contraindicated in dogs with GN, except if the underlying disease process is steroid-responsive (e.g., systemic lupus). In a retrospective study of dogs with idiopathic GN, corticosteroid treatment appeared to be detrimental, leading to azotemia and worsening of the proteinuria. If immunosuppressive drugs are initiated, the urine P:C ratio should be monitored at least monthly to assess the effects of treatment. If the magnitude of proteinuria increases, immunosuppressive therapy should be changed or discontinued.

There is increasing evidence that platelets and thromboxanes are integrally involved in the pathogenesis of GN. Beneficial responses to antiplatelet therapy with aspirin have been demonstrated in several experimental studies. Dogs with antithrombin III concentrations <70% of normal and fibrinogen concentrations >300 mg/dL are candidates for anticoagulant therapy. Antiplatelet drugs, heparin and coumadin have all been utilized here. Low-dose aspirin (0.25 mg/lb PO twice daily) has been reported to inhibit platelet aggregation in dogs and is the treatment of choice for hypercoagulability. It is unclear whether antiplatelet therapy is needed in cats with GN, because thromboembolism rarely occurs.

Treatment with enalapril decreased proteinuria, improved renal function, and prolonged survival in male Samoyeds with hereditary nephritis. Sodium-restricted diets are also strongly recommended. Protein-restricted diets improve the efficacy of enalapril treatment and are recommended to decrease glomerular hyperfiltration and the nonimmunologic progression of GN. Despite urine protein loss, dietary protein supplementation is not advisable as proteinuria can worsen. Dogs and cats with edema or ascites should be treated with cage rest and dietary sodium restriction. Paracentesis should be reserved for animals experiencing respiratory distress and abdominal discomfort. Overzealous use of diuretics (furosemide) may cause dehydration and acute renal decompensation. Plasma transfusions provide only temporary benefits.

Monitoring urine P:C ratio is important after initiating therapy. If proteinuria increases, treatment should be changed or discontinued. The serum creatinine and urea nitrogen should also be monitored. Also, as renal function deteriorates (decrease in glomerular filtration), proteinuria usually decreases. The prognosis for dogs with GN is generally poor, although early recognition and appropriate therapy can extend the lives of these patients.

References: Jergens AE, Compend Contin Educ Pract Vet 16: 102-108, 1994; Current Veterinary Therapy XII, Saunders, Phila, 1995; Current Veterinary Therapy XIII, Saunders, Phila, 1999; Ettinger SJ, Feldman EC, Textbook of Veterinary Internal Medicine, 5th edition; Saunders, Phila, 1999; Lees GF, Helman RG, Kashtan CE, et al. AJVR 60: 373-383, 1999; Rha JY, Labato MA, Ross LA, et al. JAVMA 216: 46-50, 2000.