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Randomized controlled clinical trials (RCCTs) provide the ultimate test of therapeutic effectiveness. In addition, results of properly performed RCCTs can provide data concerning the potential harmful effects and costs associated with treatments. This article addresses the need for RCCTs in veterinary nephrology and provides a background for applying the results of such studies to patients.

Dietary protein restriction has been the mainstay of conservative medical management of canine renal failure for many years. Although dietary protein restriction minimizes many signs of uremia, its potential benefits to the progression of renal failure are now being questioned. Two case scenarios of different degrees of renal failure are described; guidelines for dietary protein restriction are based on currently available scientific knowledge.

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.

Objective: To determine the potential clinical usefulness of duplex Doppler estimation of arcuate artery resistive index (a measure of intrarenal blood flow impedance) for diagnosis of aminoglycoside-induced nephrotoxicosis., Animals: 30 adult, female, mixed-breed dogs, allotted to 3 groups of 10 dogs each as: toxic dosage of gentamicin, therapeutic dosage of gentamicin, and saline solution sham equivalent in volume to that of the toxic dosage of gentamicin., Procedure: After baseline screening to establish normalcy (serum biochemical analysis, endogenous creatinine clearance determination, urinalysis, urine protein-to-creatinine ratio, urine culture, gray-scale sonography, and percutaneous ultrasound-guided renal biopsy), results of arcuate artery resistive index determination were compared with serum creatinine and urine specific gravity values on a Monday-Wednesday-Friday data collection schedule for 10 days. Endogenous creatinine clearance determination, ultrasound-guided renal biopsy, and urine culture were repeated at the end of data collection in all 3 groups., Results: Significant differences in resistive index measurements were not observed, despite clinicopathologic and renal biopsy results compatible with severe acute tubular necrosis in dogs of the toxic dosage group., Conclusions: Duplex Doppler sonography of arcuate artery blood flow impedance, expressed as the resistive index, appears to have poor clinical usefulness as a diagnostic tool in this disorder., Clinical Relevance: Normal arcuate artery resistive index values obtained in dogs for which aminoglycoside-induced nephrotoxicosis is suspected do not exclude the disorder. If abnormal arcuate artery resistive index values are obtained for such dogs, further evaluation for nephropathies other than aminoglycoside-induced nephrotoxicosis may be considered.

During the past three decades, percutaneous renal biopsy has evolved as a valuable method of clinical evaluation of patients with various forms of glomerular proteinuria and primary renal failure. The advent of automated core biopsy needles and ultrasound guidance has substantially improved the safety of needle biopsy techniques and almost eliminated the need for surgical wedge biopsy.

Rationale and Objectives: The diagnostic usefulness of gray-scale sonography was evaluated in a canine model of aminoglycoside-induced nephrotoxicosis., Methods: Sonography was performed before and during the onset and progression of nephrotoxicosis induced by administration of a toxic dosage of gentamicin. Subjective visualization of increased renal cortex echogenicity (IRCE) was objectified with digital image analysis methods. Results of both subjective and objective evaluation were correlated with clinicopathologic tests and renal cortex biopsy obtained concurrently., Results: Subjective visualization of IRCE was associated with significant nephrotoxicosis and was superior to serum creatinine elevation in nephrotoxicity detection. Objective detection of IRCE improved nephrotoxicity detection sensitivity to that of increased urine enzymuria., Conclusions: Based on the above results, subjective visualization of IRCE in patients with aminoglycoside-induced nephrotoxicity may occur before azotemia and is suggestive of significant renal dysfunction; application of digital image analysis methods may lead to earlier sonographic recognition of nephrotoxicity.

The potential diagnostic utility of the urine gamma-glutamyl transpeptidase (GGT)-to-creatinine ratio was evaluated in an experimental canine model of aminoglycoside-induced nephrotoxicity. A therapeutic dosage of gentamicin resulted in a twofold increase in the mean urine GGT-to-creatinine ratio that was not associated with clinically significant nephrotoxicity. In dogs each given a nephrotoxic dosage of gentamicin, an increase in mean urine GGT-to-creatinine ratios approximately three times baseline values preceded clinically significant abnormalities in serum creatinine, urine specific gravity, and urine protein-to-creatinine ratio. The urine GGT-to-creatinine ratio appears superior as an early indicator of aminoglycoside-induced nephrotoxicity. Further studies in canine clinical cases are warranted.

Postrenal azotemia is a potentially life-threatening consequence of urinary obstruction Its most serious consequences include fluid volume deficits, hyperkalemia, and metabolic acidosis. Immediate therapy should be directed at restoring urine flow, correcting extracellular fluid volume deficits, minimizing the cardiac toxicity of hyperkalemia, and ameliorating the cardiovascular effects of metabolic acidosis. Most patients respond quickly and completely to such therapeutic intervention.

Perineal urethrostomies are associated with complications that may mimic primary causes of feline lower urinary tract disorders. Though postoperative urethral strictures may be minimized by proficiency with an effective surgical technique, removal of the distal urethra may result in bacterial urinary tract infections in 25% to 30% of patients after surgery. Urinary tract infections caused by urease-producing microbes may induce struvite urolith formation. Thus the prophylactic benefits of minimizing recurrent urethral obstruction by urethrostomy must be weighed against a long-term predisposition to recurrent bacterial urinary tract infection and urolith formation.

A double-blind clinical study was performed to evaluate prednisolone as treatment for idiopathic feline lower urinary tract disease. No differences in response were observed in prednisolone- and placebo-treated cats.

Surgical closure may not be necessary to successfully manage all patients with ruptured urinary bladders. If the margins of the walls of tears in the bladder wall are not devitalized, and if they remain in close apposition via maintenance of the bladder lumen in a nondistended state for an appropriate period, these conditions may simulate those created by use of surgical sutures. This is not advocating an all-or-none choice. Because the clinical status of patients with ruptured urinary bladders can range from that characterized by only hematuria and dysuria to life-threatening postrenal uremia, a range of surgical and medical options should be considered.

A step-by-step priority of procedures is recommended when attempting to restore urethral patency in an obstructed male cat. In order of priority they are: (1) massage of the distal urethra, (2) attempts to induce voiding by gentle palpation of the urinary bladder, (3) cystocentesis, (4) retrograde urethral flushing, (5) combinations of 1 through 4, (6) diagnostic radiology to determine if the cause of urethral obstruction is intraluminal, mural or extramural, and if absolutely necessary, (7) surgical procedures.

Obstructive uropathy refers to abnormalities in structure or function of the urinary tract caused by impairment of normal flow of urine, and the resulting local and systemic effects of that impairment. Clinic consequences of obstructive uropathy are associated with abnormalities in fluid balance, electrolyte metabolism, acid-base balance, and retention of metabolic wastes. These consequences are partly due to build up of intravesical, ureteral, and renal pressure, influx of leukocytes into renal parenchyma resulting in release of cytokines, and alterations in intravascular hemodynamics. This article discusses pathophysiologic mechanisms and consequences of obstructive uropathy in cats.

Renal failure is an important cause of morbidity and mortality in feline patients. In human patients, intrarenal blood flow values obtained with duplex Doppler ultrasonography have been used to aid in the diagnosis and prognosis of renal failure. The purpose of this report is to present values for resistance to intrarenal blood flow in normal cats, derived by duplex Doppler ultrasonography. Ten mature clinically healthy conditioned domestic shorthaired cats were screened for normal renal anatomy and function by CBC, serum biochemical profile, urinalysis, urine protein/creatinine ratio, endogenous creatinine clearance, and renal B-mode ultrasonography; and for normal systemic blood pressure with Doppler pressure cuff measurement. Subsequently, the cats were sedated with ketamine hydrochloride, and values for mean intrarenal (arcuate artery) resistance to blood flow were determined by duplex Doppler ultrasonography, and expressed as the Pourcelot resistive index, a ratio of systolic to diastolic flow commonly used in duplex Doppler sonography in human patients. After duplex Doppler sonographic examination, histological normalcy of the kidneys was verified by evaluation of ultrasound-guided percutaneous renal biopsy. Based on the obtained resistive indices, 95% confidence intervals for normal values were calculated as follows: left kidney, 0.52 to 0.60; right kidney, 0.55 to 0.63. No statistically significant difference was noted between the values obtained for the right versus the left kidney.

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)

Background: Although still controversial, several studies in humans have suggested That dietary protein restriction may slow the rate of progression of chronic renal failure. Thus, the influence of dietary protein on renal function and progression of renal failure has been the subject of numerous studies in several animal models of chronic renal failure, including rodents, dogs, and baboons. Because of the high incidence of chronic renal failure in aged cats, and the high dietary protein requirements of cats, we studied the effects of dietary protein intake on renal function, proteinuria, and renal morphology in cats with reduced renal mass., Experimental Design: Partial (5/6) nephrectomy was performed in 14 young adult female cats. Sham surgical procedures were performed in eight control cats. Control cats and cats with 5/6 nephrectomy were randomly assigned to diets containing either 27.6% (low) or 51.7% (high) protein and studied for 1 year., Results: Renal mass reduction by 5/6 decreased glomerular filtration rate by 2/3 and significantly increased proteinuria. Cats with remnant kidneys had significantly higher systolic and mean blood pressures than control cats. Increased dietary protein/calorie intake significantly increased glomerular filtration rate and proteinuria in all cats. Glomerular filtration rates remained stable in all cats over the year of study. However, high protein/calorie intake resulted in significant renal morphologic injury in remnant kidney cats that was prevented by dietary protein/calorie restriction. Light and electron microscopic glomerular changes in remnant kidney cats fed the high protein diet were similar to changes previously reported in rats and dogs with remnant kidneys., Conclusions: Dietary protein/calorie restriction limits proteinuria and glomerular injury in cats with remnant kidneys in a fashion similar to that reported in rats. However, the remnant kidney model in the cat appeared to be associated with a slower rate of progression compared with kidney model in the cat appeared to be associated with a slower rate of progression compared with rats.

To determine the effects of long-term dietary protein restriction in cats with chronic renal failure (CRF), 4 healthy adult cats and 7 cats with surgically induced CRF were fed a high-protein (HP, 51.7% protein) diet and 4 healthy adult cats and 7 cats with surgically induced CRF were fed a low-protein (LP, 27.6% protein) diet for 1 year. Cats with induced CRF that were fed the LP diet had reduced serum urea nitrogen concentrations, despite lower glomerular filtration rates, compared with cats with CRF fed the HP diet. Despite five-sixths reduction in renal mass, reduced glomerular filtration rate, and azotemia, 13 of the 14 cats with induced CRF retained the ability to concentrate urine and produced urine with a specific gravity > 1.035. Cats fed the HP diet consumed significantly more calories than did cats fed the LP diet, presumably because the HP diet was more palatable. As a result of the lower caloric intake in cats fed the LP diet, these cats were protein and calorie restricted, compared with cats fed the HP diet. Cats fed the HP diet weighed significantly more than did cats fed the LP diet. Mean hematocrit and mean serum albumin concentration were significantly lower in control cats and in cats with CRF fed the LP diet, compared with control cats and cats with CRF fed the HP diet. Hypokalemia developed in 4 of 7 cats with CRF fed the HP diet (containing 0.3% potassium); hypokalemia did not develop in control cats fed the same diet or in cats with CRF fed the LP diet containing 0.4% potassium. Excessive kaliuresis, hypomagnesemia, and metabolic acidosis did not appear to contribute to the hypokalemia. Subsequent supplementation of the HP diet with potassium gluconate prevented hypokalemia in cats with CRF.

Urine protein/creatinine (UP/C) ratios and 24-hour urinary protein excretion were compared in clinically normal cats and cats with surgically induced chronic renal failure (CRF). Mean 24-hour urinary protein excretion in 30 clinically normal cats fed a 28% protein diet (dry weight basis) was 4.93 mg/kg/24-hour (SD = 1.34) with a range of 2.99 to 8.88. Mean UP/C ratio in these cats was 0.134 (SD = 0.037) with a range of 0.073 to 0.239. Mean 24-hour urinary protein excretion in CRF cats was 10.49 mg/kg/24-hour (SD = 11.28) with a range of 2.16 to 62.93. Mean UP/C ratio in the CRF cats was 0.359 (SD = 0.374) with a range of 0.061 to 1.916. Linear regression showed high correlation (R2 = 0.973, P less than 0.001) between 24-hour urinary protein excretion and UP/C ratio in clinically normal cats and cats with surgically induced chronic renal failure. The regression equation for 24-hour urinary protein excretion versus UP/C ratio was: 24-hour urinary protein excretion = 29.39 (UP/C) + 0.18. Results of this study indicate that UP/C ratios are a valid estimate of 24-hour urinary protein excretion in clinically normal and CRF cats. Dietary protein intake significantly affected UP/C ratios in clinically normal cats and cats with surgically induced CRF. Therefore, the influence of dietary protein should be considered when interpreting UP/C ratios.

Studies in rodents indicate that diet influences progression of renal failure. Excessive dietary intakes of protein, fat, energy and phosphorus have been implicated in promoting progression of renal failure, while restriction of some or all of these dietary constituents limits progressive renal injury. Studies confirm that renal failure is progressive in some dogs with moderate-to-advanced renal dysfunction. Recent studies also indicate that unrestricted intakes of protein promotes proteinuria in dogs and cats and glomerular injury in cats.

Twenty-four-hour excretion of urine metabolites was determined in 33 clinically normal Beagles during periods of consumption of a standard diet and when food was withheld. The goal was to determine normal canine values for urine analytes incriminated in the genesis of calcium oxalate uroliths. During periods when dogs consumed food, dairy urinary excretion of calcium, uric acid, sodium, potassium, magnesium, ammonium, and hydrogen ions were significantly (P = 0.0004, 0.0038, 0.001, 0.0001, 0.0004, 0.0001, and 0.024, respectively) higher than when food was withheld. Urinary excretion of phosphorus, oxalate, and citrate were not significantly different between samples obtained during periods of food consumption and when food was withheld. Male dogs excreted significantly higher quantities of urine oxalate than females during fed (P = 0.003) and nonfed (P = 0.003) conditions. When food was withheld, urinary uric acid excretion was significantly higher in males than females (P = 0.01). Females excreted significantly more urine calcium than males when food was withheld (P = 0.003). Our results indicated that dietary conditions influence the quantity of sodium, potassium, calcium, magnesium, and uric acid excreted in the urine of clinically normal dogs; therefore, dietary conditions should be considered when measuring the concentration of these analytes in urine.

To evaluate underlying causes of calcium oxalate urolithiasis, 24-hour excretion of urine metabolites was measured in 6 Miniature Schnauzers that formed calcium oxalate (CaOx) uroliths during periods when they were fed a standard diet and during periods when food was withheld. Serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D also were evaluated. Serum calcium concentrations were normal in all 6 affected Miniature Schnauzers; however, during diet consumption, mean 24-hour urinary excretion of calcium was significantly (P = 0.025) higher than calcium excretion when food was withheld. In 1 dog, urinary calcium excretion was lower during the period of food consumption, compared with the period when food was withheld. Compared with clinically normal Beagles, Miniature Schnauzers that formed CaOx uroliths excreted significantly greater quantities of calcium when food was consumed (P = 0.0004) and when food was withheld (P = 0.001). Miniature Schnauzers that formed CaOx uroliths excreted significantly less oxalate than clinically normal Beagles during fed (P = 0.028) and nonfed (P = 0.004) conditions. Affected Miniature Schnauzers also excreted abnormally high quantities of uric acid. Excretion of citrate was not different between Miniature Schnauzers with CaOx urolithiasis and clinically normal Beagles. In 5 of 6 Miniature Schnauzers with CaOx urolithiasis, concentrations of serum parathyroid hormone were similar to values from age- and gender-matched Miniature Schnauzers without uroliths. The concentration of serum parathyroid hormone in 1 dog was greater than 4 times the mean concentration of clinically normal Miniature Schnauzers. Mean serum concentrations of 1,25-dihydroxyvitamin D in Miniature Schnauzers with calcium oxalate urolithiasis were similar to concentrations of clinically normal Miniature Schnauzers.

Blood gas values were compared in blood collected from cut toenails and femoral arteries in 50 healthy crossbred dogs that were sedated and allowed to breathe room air spontaneously. Blood samples from cut toenails were collected by microcapillary technique with Natelson tubes. Femoral artery samples were collected by arterial puncture. Blood values for PO2, PCO2, pH, and HCO3 were compared. There was good correlation for pH, PCO2, and bicarbonate, but not for PO2. Microcapillary samples should be collected in 10 seconds or less for the most accurate results. A metal mixing "flea" was unnecessary. When properly handled, the Natelson tube technique provides an alternative method for collection of blood gas samples.

The influence of induced chronic renal failure on 24-hour urinary excretion and fractional excretion of sodium and potassium was studied in cats. Induction of chronic renal failure significantly increased fractional excretion of potassium (P less than 0.0001) and sodium (P less than 0.05); however, 24-hour urinary excretion of sodium and potassium decreased slightly following induction of chronic renal failure. Fractional excretion and 24-hour urinary excretion of sodium and potassium were compared by linear regression in clinically normal cats, cats with chronic renal failure, and clinically normal and affected cats combined. In clinically normal cats, linear regression revealed only moderate correlation between fractional excretion and 24-hour urinary excretion for sodium and potassium. Linear regression of these same relationships in cats with chronic renal failure, and in clinically normal cats and cats with chronic renal failure combined, indicated low correlation. Fractional excretions of sodium and potassium were not reliable indicators of 24-hour urinary excretion of these electrolytes in cats with chronic renal failure or unknown glomerular filtration rate. Fractional excretion of potassium and sodium correlated only moderately with 24-hour urinary excretion in clinically normal cats.

The efficacy of a diet designed to facilitate dissolution of feline magnesium ammonium phosphate (struvite) uroliths was evaluated in 30 cases of urolithiasis, sterile struvite uroliths dissolved in a mean of 36 days after initiation of dietary treatment. In 5 cases of urolithiasis, struvite urocystoliths associated with urease-negative bacterial urinary tract infection dissolved in a mean of 23 days after initiation of dietary and antimicrobial treatment. In 3 cases of urolithiasis, struvite urocystoliths associated with urease-positive staphylococcal urinary tract infection dissolved in a mean of 79 days after initiation of dietary and antimicrobial treatment. Dissolution of uroliths in cats fed the treatment diet was associated with concomitant remission of dysuria, hematuria, and pyuria, and reduction in urine pH and struvite crystalluria. In one case, a urocystolith composed of 100% ammonium urate, and in another case, a urolith composed of 60% calcium phosphate, 20% calcium oxalate, and 20% magnesium ammonium phosphate did not dissolve.

Feline lower urinary tract disease is often associated with uroliths and urethral plugs. Uroliths and urethral plugs are composed of variable quantities of matrix and a variety of minerals (including struvite, calcium oxalate, ammonium urate, calcium phosphate, and cystine). Knowledge of nutritional factors associated with the pathophysiology of uroliths and urethral plugs facilitates the modification of diets for the dissolution of several minerals contained within them.

Medical therapy is an effective method of canine struvite urolith dissolution. Recommendations include (1) eradication or control of urinary tract infection (if present), (2) use of calculolytic diets, and (3) administration of urease inhibitors to patients with persistent urinary tract infection caused by urease-producing microbes.

Urine must be oversaturated with magnesium ammonium phosphate for struvite uroliths to form. Oversaturation of urine with magnesium ammonium phosphate may be associated with several factors, including urinary tract infections with urease-producing microbes, alkaline urine, diet, and genetic predisposition. Of the urease-producing microbes, staphylococci are most struvitogenic in dogs. The precise mechanisms resulting in formation of sterile struvite uroliths in dogs have not been determined.

A maintenance diet containing 44.4% dry weight protein and 2 reduced protein diets containing 17.2% and 8.2% dry weight protein were studied in dogs with induced chronic renal failure to determine effects on their (1) clinical status, (2) renal function, (3) electrolyte and acid-base balance, (4) divalent ion balance, (5) nutritional status, (6) hematologic status, and (7) hemostasis. A cross-over design of feeding was utilized so that the effect of diet could be studied in each dog at a known state of renal dysfunction and so that reversibility of effects could be determined. The inulin clearance rate was higher when the 44.4% protein diet was fed than when the 8.2% or 17.2% protein diets were fed. However, consumption of lower protein diets was associated with greater physical activity and reduction in serum urea nitrogen concentrations, compared with consumption of the 44.4% protein maintenance diet. Varying degrees of hyperchloremic metabolic acidosis developed in dogs fed the 8.2% and 17.2% protein diets. Reduced total serum protein and albumin concentrations, and hypercholesterolemia developed in dogs fed the 8.2% protein diet. All effects were reversible after diets were changed. It was concluded that diet-induced alterations in renal function associated with moderate dietary protein restriction did not adversely effect clinical and biochemical status of dogs with renal failure. It was unclear whether the clinical and biochemical changes observed with more severe protein restriction resulted from diet-induced changes in renal function.

The influence of a canine maintenance diet containing 44.4% protein (dry weight) and 2 reduced-protein renal-failure diets containing 8.2% or 17.2% protein (dry weight) on the nutritional status of dogs with induced chronic renal failure was evaluated for 40 weeks. Nutritional status was assessed by changes in serially determined body weights, hindlimb circumferences, serum protein concentrations, complete blood cell counts, serum cholesterol concentrations, glucose tolerance tests, and blood glucose concentrations. Evidence of suboptimum nutritional status was observed in dogs fed the 8.2% or 44.4% protein diets, but not in dogs fed the 17.2% protein diet. Only a small reduction in hindlimb circumference developed in dogs fed the 17.2% protein diet. Reduced body weight and hindlimb circumference and normocytic normochromic anemia developed in dogs fed the 44.4% protein diet. Reduced body weight and hindlimb circumference, hypoalbuminemia, hypoproteinemia, hypercholesterolemia, and normocytic normochromic anemia developed in dogs fed the 8.2% protein diet. A beneficial effect of moderate dietary protein restriction (17.2% protein) on the nutritional status of the dogs was observed. In contrast, excessive intake or restriction of dietary protein was associated with detrimental effects.

The influence of a maintenance diet (44.4% dry weight protein) and 2 reduced protein diets (8.2 and 17.2% dry weight protein) on acid-base, electrolyte, and divalent ion balance of dogs with experimentally induced chronic renal failure was studied for 40 weeks. Moderate-to-severe hyperchloremic metabolic acidosis developed in dogs fed the 8.2% protein diet, but not in the groups fed the 17.2% and 44.4% protein diets. Serum sodium and potassium concentrations were not altered significantly by the diets. Mean serum calcium concentrations increased significantly in the 3 groups after renal failure was induced; however, serum calcium concentration generally did not exceed the normal range. Dogs fed reduced protein diets had smaller serum magnesium and phosphorus concentrations than did the dogs fed the maintenance diet. Microscopic alterations in bone morphology consistent with canine renal osteodystrophy were not detected after 40 weeks of renal failure in dogs fed the 17.2% and 44.4% protein diets. Examination of skull radiographs of the dogs prepared 40 weeks after renal failure was induced revealed that the lamina dura dentes were visible in all groups. It was concluded that the 8.2% protein diet was of therapeutic benefit in management of altered divalent ion metabolism in dogs with chronic renal failure. However, the high frequency of concomitant acidosis indicated that appropriate alkalinization therapy should be included with this diet. Adverse effects of feeding the 17.2% protein diet were not detected. However, it was less effective than the 8.2% protein diet in minimizing development of hypermagnesemia and skeletal changes consistent with renal osteodystrophy.

Distal RTA is characterized by decreased distal renal tubular hydrogen ion secretion, decreased ability to acidify urine, hypercalciuria, hyperphosphaturia, hypocitraturia, and metabolic acidosis. Because of the resulting alterations in urine composition and pH, patients with distal RTA are predisposed to urolithiasis and renal calcification. Diagnosis of distal RTA is important because it is a potentially reversible disorder that, left untreated, may cause nephrocalcinosis, recurrent urolith formation, moderate to severe metabolic acidosis, and renal failure.

Nutritional therapy is the mainstay of management of chronic renal failure in dogs and cats. Diets designed for use in renal failure are typically reduced in protein, phosphorus, and sodium content. These and other dietary modifications are designed to prevent or ameliorate clinical signs of uremia, minimize disturbances associated with excesses or losses of electrolytes and minerals, arrest or retard progression of renal failure, and maintain adequate nutrition.

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.

Mixed acid-base disturbances are combinations of two or more primary acid-base disturbances. Mixed acid-base disturbances may be suspected on the basis of findings obtained from the medical history, physical examination, serum electrolytes and chemistries, and anion gap. The history, physical examination, and serum biochemical profile may reveal disease processes commonly associated with acid-base disturbances. Changes in serum total CO2, serum potassium and chloride concentrations, or increased anion gap may provide clues to the existence of acid-base disorders. Blood gas analysis is usually required to confirm mixed acid-base disorders. To identify mixed acid-base disorders, blood gas analysis is used to identify primary acid-base disturbance and determine if an appropriate compensatory response has developed. Inappropriate compensatory responses (inadequate or excessive) are evidence of a mixed respiratory and metabolic disorder. The anion gap is also of value in detecting mixed acid-base disturbances. In high anion gap metabolic acidosis, the change in the anion gap should approximate the change in serum bicarbonate. Absence of this relationship should prompt consideration of a mixed metabolic acid-base disorder. Finding an elevated anion gap, regardless of serum bicarbonate concentration, suggests metabolic acidosis. In some instances, elevated anion gap is the only evidence of metabolic acidosis. In patients with hyperchloremic metabolic acidosis, increases in the serum chloride concentration should approximate the reduction in the serum bicarbonate concentration. Significant alterations from this relationship also indicate that a mixed metabolic disorder may be present. In treatment of mixed acid-base disorders, careful consideration should be given to the potential impact of therapeutically altering one acid-base disorder without correcting others.

Mebendazole was administered to 7 adult Dachshunds and 2 adult Doberman Pinschers at 6-month intervals for routine parasite control. Two weeks after the 1st treatment, a 3-year-old Dachshund died of acute hepatic failure. Approximately 2 weeks following the 2nd treatment, two 5-year-old Dachshunds and one 3-year-old Dachshund had evidence of acute hepatic necrosis; 1 of these dogs died of fulminant hepatic failure. Typical clinical signs in affected dogs included anorexia, depression, vomiting, icterus, and hemorrhagic diarrhea. Two additional Dachshunds had biochemical evidence of hepatic dysfunction, ie. high serum alanine aminotransferase and serum alkaline phosphatase activities. One Dachshund and 2 Doberman Pinschers had no clinical or laboratory evidence of hepatic disease.

The influence of a maintenance diet containing 44.4% dry weight protein and 2 reduced protein diets containing 8.2% and 17.2% dry weight protein on morbidity, mortality, and renal function of dogs with induced chronic renal failure was studied for 40 weeks. The diets differed in mineral and electrolyte composition in addition to differences in protein, carbohydrate, and fat content. Dogs fed the 44.4% protein diet had a higher mortality (6 of 11) than did dogs fed the 8.2% (1 of 6) or 17.2% (0 of 6) protein diets. Dogs fed the 44.4% protein diet died of uremic complications. An occlusive portal vein thrombus caused death of the nonsurvivor fed the 8.2% protein diet. Clinical signs of uremia were detected only in nonsurvivors fed the 44.4% protein diet. Surviving dogs fed the maintenance diet were less active and had poorer hair than did dogs fed reduced protein diets. Inulin clearance rate and urinary protein excretion were lower in most dogs fed reduced protein diets than in dogs fed the maintenance diet. Despite the greater decrease in renal function, serum urea nitrogen concentrations were markedly lower in dogs fed the 8.2% and 17.2% protein diets than in dogs fed the 44.4% protein diet. Seemingly, the reduced protein renal failure diets were of benefit in preventing or reducing morbidity and mortality associated with the uremic syndrome and in reducing serum urea nitrogen concentrations as compared with that of the higher protein diet. The potential benefits of dietary protein restriction in dogs with chronic renal failure prevailed over potential adverse affects of excessive protein consumption.

Nutritional factors play a variable role in the etiopathogenesis of canine struvite, ammonium urate, cysteine, calcium oxalate, and silica uroliths. Knowledge of these factors allows modification of diets to promote dissolution of selected minerals within uroliths.

The effects of two reduced-protein diets and a canine maintenance diet on renal function, nutrition, serum and urine acid-base and electrolyte values, and divalent ion metabolism were compared in Beagle dogs with induced chronic renal failure. Two reduced-protein (18%) diets differed in their protein sources. One 18% protein diet was formulated using egg protein as the only protein source. The other 18% protein diet was formulated using a mixture of animal and vegetable proteins. The 42% protein diet contained a mixture of animal and vegetable protein sources. Results of this study indicate that the egg-based and mixed protein-based diets had similar effects on most clinical and laboratory evaluations in dogs with chronic renal failure. However, the egg protein diet appeared to promote hyperchloremic metabolic acidosis. Both reduced-protein diets were beneficial in reducing azotemia, polyuria, hypermagnesemia, and fractional excretion of phosphorus compared with the 42% protein diet.

This case is typical of recurrent urolithiasis managed by repeated surgery. Retrospective assessment of the disorder indicates the need for quantitative analyses of uroliths removed by cystotomy. Compliance of the owners with recommendations to minimize recurrent urolithiasis might have been beneficial. Results of medical therapy designed to induce dissolution of uroliths in this case are representative of preliminary findings of medical dissolution of naturally occurring struvite uroliths in ten other cats. It is of interest that the uroliths dissolved even though no effort was made to induce diuresis. The underlying cause of UTI in this patient may have been damage to the lower urinary tract induced by previous diagnostic and therapeutic procedures and/or sterile struvite uroliths that compromised local host defense mechanisms. Lack of urease production by the uropathogens suggests that they did not play a causative role in formation of uroliths. The need for preventative therapy of recurrent formation of uroliths after their medical dissolution is worthy of further comment. In this patient, specific measures to prevent urolith recurrence were not initiated because it is a part of a prospective clinical study. In the event uroliths recur, medical therapy designed to induce dissolution of uroliths would be repeated. Need for long-term preventative therapy would be dependent on the time interval between recurrent episodes (weeks, months, or years), and the effectiveness of medical therapy for urolith dissolution. Long-term prophylactic therapy would include urine acidifiers and diets low in magnesium.

Obstruction to urine outflow is a common complication of urolithiasis. However, varying degrees of recovery of renal function may occur following examination of the cause of obstruction. Therefore, in the absence of conclusive evidence of irreversible dysfunction, one should consider efforts to decompress the urinary tract and to eliminate the cause of obstruction. Nonsurgical methods that may be used for management of obstructive urolithiasis include cystocentesis, palpation, urohydropropulsion, and catheterization.

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.