Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism.

BACKGROUND: Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism. OBJECTIVES: To investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats. ANIMALS: Two hundred and sixty-two hyperthyroid cats and 206 aged-matched, clinically normal cats. METHODS: Prospective study. We measured creatinine, urea nitrogen, SDMA, T4 , and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131 I) and classified 131 I-treated cats as azotemic or nonazotemic based on persistent, post-treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression. RESULTS: No hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4-8 months (median, 6 months) after 131 I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre-azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%. CONCLUSIONS AND CLINICAL IMPORTANCE: Finding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false-positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).

Clinical Consequences of Hypertriglyceridemia-Associated Proteinuria in Miniature Schnauzers.

BACKGROUND: Primary hypertriglyceridemia is a common condition in older Miniature Schnauzers that recently has been associated with proteinuria and underlying glomerular pathology, particularly glomerular lipid thromboemboli. Consequences of glomerular disease can include hypertension, thromboembolic disease, and cardiac disease. The incidence of these sequelae in Miniature Schnauzers with hypertriglyceridemia-associated proteinuria (HTGP) is unknown. OBJECTIVE: To investigate prevalence of hypertension, decreased antithrombin III activity, and cardiac disease in Miniature Schnauzers with and without HTGP. ANIMALS: Thirty-two Miniature Schnauzers ≥7 years old. METHODS: Prospective case-control study. Data collected from dogs included a CBC, biochemistry panel, urinalysis, urine protein-to-creatinine ratio, urine cortisol-to-creatinine ratio, serum total thyroxine concentration, fasting serum triglyceride concentration, indirect blood pressure, antithrombin III activity, and serum cardiac troponin I concentration. Results from dogs with HTGP (serum triglyceride concentration ≥ 100 mg/dL and urine protein-to-creatinine ratio >0.5) were statistically compared to normotriglyceridemic, nonproteinuric dogs. RESULTS: Eighteen of the 32 dogs (56%) had primary hypertriglyceridemia. Of those dogs, 8 of 18 had proteinuria. None of the HTGP dogs were azotemic or hypoalbuminemic. Serum albumin concentration, alkaline phosphatase activity, and cholesterol concentration were significantly increased in dogs with HGTP compared to those without HGTP. No increased risk of hypertension, decreased antithrombin III activity, or cardiac disease was noted. Limited data from 8 dogs with HTGP showed no development of hypoalbuminemia or azotemia over a median follow-up period of 18 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Geriatric Miniature Schnauzers with HGTP may have a good prognosis overall, and are not typically azotemic or hypoalbuminemic.

World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

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.

Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement.

OBJECTIVES: There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised. METHODS: Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species. RESULTS: Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD. DISCUSSION: The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.

Consensus recommendations for immunosuppressive treatment of dogs with glomerular disease based on established pathology.

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.

An evidence-based review of therapies for canine chronic kidney disease.

Successful treatment and prevention of kidney disease in dogs requires a multi-dimensional approach to identify and eliminate causes or exacerbating factors, provide professional evaluation on a regular basis and implement a comprehensive treatment programme when necessary. Over the years, many therapeutic and preventive interventions have been developed or advocated for chronic kidney disease in dogs, but evidence of efficacy or effectiveness is often lacking or highly variable. Accordingly, the main objective of this systematic review was to identify and critically appraise the evidence supporting various aspects of managing canine chronic kidney disease.

Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs.

BACKGROUND: A major cause of death in dogs with immune-mediated hemolytic anemia (IMHA) is thromboembolism. Previous studies suggest unfractionated heparin (UH) is not effective in preventing thromboembolism in IMHA; however, subtherapeutic dosing could explain the seeming lack of efficacy. HYPOTHESIS: Providing therapeutic plasma concentration of UH by individually adjusting doses based on antifactor Xa activity would improve survival in IMHA. ANIMALS: Fifteen dogs with primary IMHA. METHODS: Randomized, prospective, controlled clinical trial. Dogs received standardized therapy for IMHA and either constant dose (CD) (150 U/kg SC) (n = 7) or individually adjusted dose (IAD) (n = 8) UH, monitored via an anti-Xa chromogenic assay, adjusted according to a nomogram. UH was administered every 6 hours until day 7, and every 8 hours thereafter. UH dose was adjusted daily in IAD dogs until day 7, weekly until day 28, then tapered over 1 week. Dogs were monitored for 180 days. RESULTS: At day 180, 7 dogs in the IAD group and 1 in the CD group were alive (P= .01). Median survival time for the IAD group was >180 days, and 68 days for the CD group. Thromboembolic events occurred in 5 dogs in the CD group and 2 dogs in the IAD group. Doses of UH between 150 and 566 U/kg achieved therapeutic anti-Xa activity (0.35-0.7 U/mL). CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that IAD UH therapy using anti-Xa monitoring reduced case fatality rate in dogs with IMHA when compared with dogs receiving fixed low dose UH therapy.

Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis.

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.

Dietary management of feline chronic renal failure: where are we now? In what direction are we headed?

Dietary modification is of primary importance in managing cats with chronic renal failure. Diets designed for cats with chronic renal failure are typically formulated to be pH neutral and contain reduced quantities of protein, phosphorus and sodium and an increased quantity of potassium. These changes in diet formulation are designed to ameliorate clinical signs of renal failure by adapting dietary intakes to meet the limited ability of failing kidneys to adapt to the normal range of dietary intakes. Important recent clinical trials support the therapeutic value of dietary therapy in cats with chronic renal failure.

Age and diet effects on relative renal echogenicity in geriatric bitches.

Under controlled, but varied dietary conditions 35 geriatric, uninephrectomized, spayed Beagle bitches (dogs) observed for 4 years, renal cortical and renal medullary echogenicity was measured relative to hepatic and splenic echogenicity. Regardless of the diet fed, 60-75% of these aged dogs had renal cortical echogenicity less than that of either the liver or spleen across time; 25-35% of these dogs had renal cortical echogenicity equal to that of the liver, but less than that of the spleen across time. Less than 3% of these dogs had renal cortical echogenicity greater than that of the liver, but less than that of the spleen. Only 1 (one) of these dogs had renal cortical echogenicity equal to that of the spleen and that occurred at only one of the 14 chronologic assessments. Therefore, in either mature or aged dogs imaged with 4.0 to 5.0 MHz equipment, the renal cortical echogenicity should be considered normal if it is less than or equal to that of the liver and less than that of the spleen. In 29 dogs imaged with the 4.0/5.0 MHz equipment and 6 dogs imaged with 7.5 MHz equipment, there was no significant diet or individual dog effect. The 7.5 MHz (6 dog) group had significantly higher average cortical echogenicity scores than the 4.0/5.0 MHz (29 dog) group. However, the occurrence of renal cortical echogenicity greater than liver echogenicity was seen in only 5 of 83 samples (approximately 6.0%) made on 6 dogs imaged with 7.5 MHz equipment and only 1 of 375 samples (approximately 0.27%) made on 29 dogs with 4.0/5.0 MHz equipment. With the exception of one occurrence, all dogs had renal medullary echogenicity less than that of the liver or spleen regardless of imaging equipment frequency. The renal medulla was always hypoechoic compared to the cortex.

Effects of diet and aging on renal measurements in uninephrectomized geriatric bitches.

Under controlled, but varied dietary conditions among geriatric, uninephrectomized Beagle bitches (dogs) observed for 4 years, renal size increase as assessed radiographically and ultrasonographically occurred at variable rates, but on a seemingly continuous basis. The maximum observed mean renal linear parameter increase found was approximately 15%. However, a 10 and 15% increase is a more representative expectation among the 4 parameters (sonographic length, radiographic length, sonographic width, radiographic width) under consideration. The rate of renal size increase was rapid during the first 2 to 3 months following uninephrectomy. Thereafter, the rate of increase was slow, but occurred to varying degrees in both the length and width as assessed radiographically or ultrasonographically. The mechanism creating the size change was hypertrophy, not hyperplasia. Within limits of the 3 diets used in the study, no significant diet effect was found on the rate or degree of long term compensatory hypertrophy. Radiographically and ultrasonographically measured renal length had the greatest correlation with each other as well as with post mortem measurements and are, therefore, the recommended parameter for imaging assessment of compensatory hypertrophy. When the prenephrectomy, radiographic renal lengths and widths were normalized as a ratio of the second lumbar vertebral body length (L2) measured from ventrodorsal radiographs, the diet group means across dogs (approximately three L2 lengths for renal length; two L2 lengths for renal width) were in the middle of the respective previously published normal radiographic ranges for mature dogs (e.g. 2.5 L2 < or = length < or = 3.5 L2; 1.58 L2 < or = width < or = 2.38 L2 lengths). Even after the hypertrophic changes occurred, the radiographic group mean lengths and widths across dogs were still within the specified normal ranges, although toward the upper end of the respective range. This information provides background for clinical interpretation of potential compensatory hypertrophy that may be encountered following uninephrectomy for spontaneous disease in aged dogs. In addition, it appears that available radiographic renal linear ranges for normal mature dogs are applicable to geriatric dogs as well.

Analysis of 77,000 canine uroliths. Perspectives from the Minnesota Urolith Center.

Of the hundreds of minerals that are found in the earth, most canine uroliths are comprised of only six types: (1) magnesium ammonium phosphate, (2) calcium oxalate, (3) calcium phosphates, (4) ammonium urate and other salts or uric acid, (5) cystine, or (6) silica. Each type has characteristics that allow its identification. During the past two decades, the prevalence of calcium oxalate canine uroliths has dramatically increased, while struvite has decreased. The most effective treatment and prevention protocols are based on knowledge of the primary mineral type comprising the urolith.

Medical dissolution and prevention of canine struvite urolithiasis. Twenty years of experience.

Two types of canine struvite uroliths have been recognized: infection-induced struvite is the most common type; sterile struvite is uncommonly recognized. Infection-induced struvite is most commonly associated with urease-producing staphylococcal UTI. For dogs that qualify, medical dissolution is an effective method of treatment. Medical dissolution protocols encompass: (1) eradication or control of UTI; (2) use of calculolytic diets; and (3) administration of urease inhibitors to patients with persistent UTI caused by urease-producing microbes.

Canine and feline nephrolithiasis. Epidemiology, detection, and management.

Calcium oxalate (39%) and struvite (33%) were the predominant mineral types in canine nephroliths submitted to the Minnesota Urolith Center. Urate salts (12%) and calcium phosphate (2%) occurred less frequently. Provided they are not causing obstruction, struvite nephroliths may be dissolved with medical protocols. Although there are no dissolution protocols for nephroliths containing calcium, risk-benefit ratios should be considered before proceeding with surgery.

Canine retrograde urohydropropulsion. Lessons from 25 years of experience.

Uroliths are commonly voided into the urethra where they often lodge adjacent to the os penis in male dogs. Urethral patency can, with few exceptions, be restored by flushing uroliths back into the bladder lumen by retrograde urohydropropulsion. To be consistently successful, one must be familiar with the concepts of the procedure and each step of the technique.

Clinical disorders of potassium homeostasis. Hyperkalemia and hypokalemia.

Potassium plays an important role in cell metabolism and membrane excitability. Disorders of potassium balance can have profound clinical effects, particularly on the cardiovascular and neuromuscular systems. Chronic hyperkalemia invariably results from impaired renal potassium excretion. Hyperkalemia can be a potentially life-threatening disturbance requiring emergency intervention. Treatment is usually directed at correcting the defect in potassium excretion. Hypokalemia has become closely linked with in cats. Clinical signs include muscle weakness and renal dysfunction, which usually respond well to oral potassium supplementation.

Duplex doppler estimation of intrarenal pourcelot resistive index in dogs and cats with renal disease.

In human beings, intrarenal blood flow impedance, expressed as the resistive index (RI) and obtained by duplex Doppler ultrasonography, has been used to aid in diagnosis and prognosis of renal failure. Higher than normal values for RI were obtained in 3 of 4 dogs with acute tubular necrosis (ATN) and in 5 of 10 dogs with glomerulonephrosis (GN). Normalization of RI was observed in 2 dogs with ATN evaluated serially during treatment. Increased RI values were obtained in 9 of 10 cats with nonobstructive renal disease and in 2 of 5 cats with obstructive renal disease. Normalization of RI was observed in 3 cats with renal failure in which treatment was effective (1 with obstruction; 2 with nonobstructive disease). The magnitude of increase in RI did not correlate with the magnitude of concurrent renal dysfunction. These results suggest that duplex Doppler evaluation of intrarenal RI is more useful as an ancillary diagnostic technique in azotemic dogs with ATN than in those with GN and in azotemic dogs with nonobstructive than in those with obstructive disease.