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Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed., (© The Author(s) 2015.)

Background: In certain situations, veterinarians must decide whether or not to recommend immunosuppressive therapy for dogs with suspect glomerular disease in the absence of renal biopsy-derived evidence that active immune mechanisms are contributing to glomerular injury. The purpose of this report is to provide guidelines for the use of immunosuppressive drugs under these conditions., Animals: Animals were not used in this study., Methods: Recommendations were developed by a formal consensus method., Results: Four recommendations were developed and accepted at a high level of consensus (median 92.5% agreement). Renal biopsy should not be performed when contraindications are present or when results will not alter treatment or outcome. Immunosuppressive drugs should not be given when the source of proteinuria is unknown, they are otherwise contraindicated, or a familial nephropathy or amyloidosis is likely. However, they should be considered when dogs are already being given standard therapy and the serum creatinine is >3.0 mg/dL, azotemia is progressive, or hypoalbuminemia is severe. Thorough client communication regarding pros and cons of such treatment as well as close and careful patient monitoring is required., Conclusion and Clinical Importance: These recommendations can help guide the decision about renal biopsy in patients with proteinuria as well as the use of immunosuppressive drugs in those patients where the decision was made not to perform renal biopsy., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

The purpose of this report was to provide consensus recommendations for the use of immunosuppressive therapy in dogs with active glomerular diseases. Recommendations were developed based on comprehensive review of relevant literature on immunosuppressive therapy of glomerular disease in dogs and humans, contemporary expert opinion, and anecdotal experience in dogs with glomerular disease treated with immunosuppression. Recommendations were subsequently validated by a formal consensus methodology. The Study Group recommends empirical application of immunosuppressive therapy for dogs with severe, persistent, or progressive glomerular disease in which there is evidence of an active immune-mediated pathogenesis on kidney biopsy and no identified contraindication to immunosuppressive therapy. The most compelling evidence supporting active immune-mediated mechanisms includes electron-dense deposits identified with transmission electron microscopic examination and unequivocal immunofluorescent staining in the glomeruli. For diseases associated with profound proteinuria, attendant hypoalbuminemia, nephrotic syndrome, or rapidly progressive azotemia, single drug or combination therapy consisting of rapidly acting immunosuppressive drugs is recommended. The Study Group recommends mycophenolate alone or in combination with prednisolone. To minimize the adverse effects, glucocorticoids should not be used as a sole treatment, and when used concurrently with mycophenolate, glucocorticoids should be tapered as quickly as possible. For stable or slowly progressive glomerular diseases, the Study Group recommends mycophenolate or chlorambucil alone or in combination with azathioprine on alternating days. Therapeutic effectiveness should be assessed serially by changes in proteinuria, renal function, and serum albumin concentration. In the absence of overt adverse effects, at least 8 weeks of the rapidly acting nonsteroidal drug therapy and 8-12 weeks of slowly acting drug therapy should be provided before altering or abandoning an immunosuppressive trial., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Standard therapy forms the basic foundation for care of dogs with glomerular disease, as it is herein recommended for use in all affected animals regardless of causation of the disease. Consensus recommendations target the evaluation and management of proteinuria, inhibition of the renin-angiotensin-aldosterone system, modification in dietary intake with special consideration for those nutrients with renal effects, diagnosis and treatment of systemic hypertension, and evaluation and management of body fluid volume status in dogs with glomerular disease., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

A blinded, multicenter, prospective clinical trial assessed the effects of enalapril (EN) versus standard care in dogs with naturally occurring, idiopathic glomerulonephritis (GN). Twenty-nine adult dogs with membranous (n = 16) and membranoproliferative (n = 13) GN were studied. Dogs were randomly assigned to receive either EN (0.5 mg/kg PO q12-24h; n = 16) or placebo (n = 14) for 6 months (1 dog was treated first with the placebo and then with EN). All dogs were treated with low-dose aspirin (0.5-5 mg/kg PO q12-24h) and fed a commercial diet. At baseline, serum creatinine (SrCr), systolic blood pressure (SBP), and glomerular histologic grade were not different between groups, but the urine protein/creatinine ratio (UP/C) was greater in the EN group compared with the placebo group (8.7 +/- 4.4 versus 4.7 +/- 2.3). After 6 months of treatment, the change in UP/C from baseline was significantly different between groups (EN = -4.2 +/- 1.4 versus 1.9 +/- 0.9 in the placebo group). When data were adjusted for changes in SrCr (SrCr X UP/C) a similar significant reduction was noted ( 2.2 +/- 15.2 versus 8.4 +/- 10.1). The change in SBP after 6 months of treatment also was significantly different between groups (EN = -12.8 +/- 27.3 versus 5.9 +/- 21.5 mm Hg in the placebo group). Response to treatment was categorized as improvement (assigned a value of 2), no progression (assigned a value of 1), and progression (assigned a value of 0). Response was significantly better in the EN group (1.4 +/- 0.8) compared with the placebo group (0.3 +/- 0.5). These results suggest that EN treatment is beneficial in dogs with naturally occurring idiopathic GN.

Protein-losing glomerulonephropathy can be a challenging disease for veterinarians to manage. This case-based article illustrates long-term management of protein-losing glomerulonephritis in a dog. Prolonged survival of this patient was attributed to early diagnosis and carefully planned therapeutic intervention consisting of dietary protein reduction and modulation of blood pressure with angiotensin converting enzyme inhibition.

Glomerulonephritis (GN) is a leading cause of chronic renal failure in dogs. However, little is known about the efficacy of available treatment options for GN in this species. The purpose of this study was to determine the effects of cyclosporine (Cy) administration on the outcome of naturally occurring GN in dogs. Thirteen dogs from 4 institutions were included in the study. Randomization of dogs into placebo-versus Cy-treated groups was stratified according to initial morphological diagnosis and contributing institution. Seven and 6 dogs were assigned to be given placebo or Cy, respectively. The initial Cy dose of 10 mg/kg every 24 hours was adjusted to maintain 24-hour trough, whole blood Cy concentrations between 250 and 400 ng/mL. There were no statistically significant differences between placebo- and Cy-treated groups with respect to serum total protein, albumin, urea nitrogen and creatinine, and plasma protein concentrations; platelet count; urine protein-creatinine ratio; endogenous creatinine clearance; 24-hour urine protein concentrations; or 24-hour urine protein-endogenous creatinine clearance ratio. However, PCV was significantly lower in the Cy-treated group. Decreased appetite, diarrhea, vomiting, weight loss, involuntary shaking, and thrombocytopenia were noted in both treatment groups; however, clinical signs in Cy-treated dogs subjectively were more severe. One Cy-treated dog developed gingival hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal failure was induced in 15 normal Beagle dogs by ligation of approximately 5/6 of the renal arteries of the left kidney and contralateral nephrectomy in order to determine how: (a) 11/12 reduction in total renal mass influences urine protein excretion and renal morphology in dogs, and (b) dietary protein intake influences renal function, urine protein excretion, and renal morphology in canine renal failure. Dogs were fed a reduced protein diet for 12 weeks after induction of renal failure, while compensatory renal hypertrophy developed. Renal function was then evaluated and dogs were distributed into 2 groups with approximately equal degrees of renal dysfunction. One group was fed a high protein diet (42% protein) and a second group was fed moderately restricted protein diets (18% protein). After 8 weeks, renal function, magnitude of proteinuria, and renal morphology were re-evaluated. Inulin clearance increased in all dogs fed the 42% protein diet and 3 of 10 dogs fed the 18% protein diets. Proteinuria was significantly greater in dogs fed the high protein diet than dogs fed the reduced protein diets. Compared with previously nephrectomized contralateral control kidneys, glomerular sclerosis and renal interstitial lesions had developed in all dogs, regardless of severity of renal dysfunction or diet fed. Although reduced dietary protein intake did not prevent development of renal lesions, renal lesions were significantly more severe in the 5 dogs fed the 42% protein diet and 3 dogs fed the 18% protein diets in which inulin clearance increased, than in 7 dogs fed the reduced protein diets in which inulin clearance did not increase.

Renal specimens obtained by biopsy and/or at necropsy from 4 dogs with nephrotic syndrome were studied using light, immunofluorescence, and electron microscopies. The glomerulonephritis observed in these dogs was considered an idiopathic immune complex glomerulonephritis associated with multisystem involvement because causes of glomerulonephritis in these dogs could not be established. Immunoglobulin A was observed in granular deposits in the mesangial and subendothelial regions of the glomeruli. The relationship of the clinical and pathologic features of this disease in dogs to various renal syndromes in human beings are described.