Presumed masitinib-induced nephrotic syndrome and azotemia in a dog.

Masitinib mesylate is a tyrosine-kinase inhibitor approved for the treatment of nonresectable or recurrent, Grade 2 or 3 mast cell tumors in dogs. This report describes nephrotic syndrome and acute kidney injury attributed to masitinib and illustrates the need for regular monitoring of serum creatinine concentration, urinalysis, and urine protein:creatinine ratio during its use.

Présomption de syndrome néphrotique et d'azotémie induits par le masitinib chez un chien. Le mésylate de masitinib est un inhibiteur de la tyrosine-kinase homologué pour le traitement des mastocytes non résécables ou récurrents de grade 2 ou 3 chez les chiens. Ce rapport décrit le syndrome néphrotique et une blessure aiguë au rein attribués au masitinib et illustre le besoin d'une surveillance régulière de la concentration sérique de créatinine, des analyses d'urine et du ratio protéine:créatinine urinaire durant son utilisation.(Traduit par Isabelle Vallières).

Urinary neutrophil gelatinase-associated lipocalin in dogs with stable or progressive kidney disease.

BACKGROUND: Active kidney injury may play a role in chronic kidney disease (CKD) progression in dogs. Neutrophil gelatinase-associated lipocalin (NGAL), a novel tubular kidney injury biomarker, may help differentiate progressive CKD from stable CKD in dogs. OBJECTIVES: To determine if urinary NGAL : creatinine ratio (UNCR) differentiates stable and progressive CKD in dogs. We hypothesized that UNCR would be higher in dogs with progressive CKD versus stable CKD. ANIMALS: Twenty-one healthy control dogs, 22 with prerenal azotemia, 19 with stable CKD, 30 with progressive CKD, and 27 with acute kidney injury (AKI). METHODS: Prospective study. Azotemic (serum creatinine concentration >1.6 mg/dL) dogs or nonazotemic AKI dogs were enrolled and classified into 4 groups: (1) prerenal azotemia, (2) stable CKD, (3) progressive CKD, and (4) AKI. Urinary NGAL was measured by ELISA and UNCR compared among groups. Urine protein : creatinine ratio (UPC) in dogs with stable and progressive CKD was compared to UNCR for differentiating CKD groups. RESULTS: UNCR was significantly higher in dogs with progressive CKD than stable CKD. UNCR of the prerenal azotemia group was significantly lower than that of the progressive CKD and AKI groups. No significant difference was found in UNCR between stable CKD and prerenal azotemia groups. ROC curve analysis of UNCR for differentiating progressive CKD from stable CKD resulted in an AUC of 0.816 (95% confidence interval [CI], 0.673-0.959), greater than that of UPC (0.696; 95% CI, 0.529-0.863). CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary NGAL could be helpful to predict the risk of progression in dogs with CKD.

A case-control study of the effects of nephrolithiasis in cats with chronic kidney disease.

OBJECTIVE: To determine whether nephrolithiasis was associated with an increase in mortality rate or in the rate of disease progression in cats with naturally occurring stage 2 (mild) or 3 (moderate) chronic kidney disease. DESIGN: Retrospective case-control study. ANIMALS: 14 cats with stage 2 (mild) or 3 (moderate) chronic kidney disease (7 with nephroliths and 7 without). PROCEDURES: All cats were evaluated every 3 months for up to 24 months. Possible associations between nephrolithiasis and clinicopathologic abnormalities, incidence of uremic crises, death secondary to renal causes, and death secondary to any cause were evaluated. RESULTS: There were no clinically important differences in biochemical, hematologic, or urinalysis variables between cats with and without nephroliths at baseline or after 12 and 24 months of monitoring. No associations were detected between nephrolithiasis and rate of disease progression, incidence of uremic crises, or death. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in cats with mild or moderate chronic kidney disease, nephrolithiasis was not associated with an increase in mortality rate or in the rate of disease progression. Findings support recommendations that cats with severe kidney disease and nephrolithiasis be managed without surgery.

Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats.

Objective-To determine whether a renal diet modified in protein, phosphorus, sodium, and lipid content was superior to an adult maintenance diet in minimizing uremic episodes and mortality rate in cats with stage 2 or 3 chronic kidney disease (CKD). Design-Double-masked, randomized, controlled clinical trial. Animals-45 client-owned cats with spontaneous stage 2 or 3 CKD. Procedures-Cats were randomly assigned to an adult maintenance diet (n = 23 cats) or a renal diet (22) and evaluated trimonthly for up to 24 months. Efficacy of the renal diet, compared with the maintenance diet, in minimizing uremia, renal-related deaths, and all causes of death was evaluated. Results-Serum urea nitrogen concentrations were significantly lower and blood bicarbonate concentrations were significantly higher in the renal diet group at baseline and during the 12- and 24-month intervals. Significant differences were not detected in body weight; Hct; urine protein-to-creatinine ratio; and serum creatinine, potassium, calcium, and parathyroid hormone concentrations. A significantly greater percentage of cats fed the maintenance diet had uremic episodes (26%), compared with cats fed the renal diet (0%). A significant reduction in renal-related deaths but not all causes of death was detected in cats fed the renal diet. Conclusions and Clinical Relevance-The renal diet evaluated in this study was superior to an adult maintenance diet in minimizing uremic episodes and renalrelated deaths in cats with spontaneous stage 2 or 3 CKD.

Controversies in Veterinary Nephrology: Renal Diets Are Indicated for Cats with International Renal Interest Society Chronic Kidney Disease Stages 2 to 4: The Pro View.

Renal diets have been the mainstay of therapy for cats with chronic kidney disease (CKD) for many decades. Clinical trials in cats with CKD have shown them to be effective in improving survival, reducing uremic crises, and improving serum urea nitrogen and phosphorous concentrations. It has shown that, when food intake is adequate, renal diets can maintain body weight and body condition scores for up to 2 years. Although some have questioned whether renal diets provide adequate protein and have advocated feeding higher-protein diets to cats with CKD, there is currently no convincing evidence in support of this proposal.

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats.

Evaluation of the association between initial proteinuria and morbidity rate or death in dogs with naturally occurring chronic renal failure.

OBJECTIVE: To determine whether urine protein-to-creatinine ratio (UP:C) > or = 1.0 at initial diagnosis of chronic renal failure (CRF) is associated with greater risk of development of uremic crises, death, and progression of renal failure in dogs. DESIGN: Prospective cohort study. ANIMALS: 45 dogs with CRF PROCEDURE: Dogs were prospectively assigned to 2 groups on the basis of initial UP:C < 1.0 or 2 > or = 1.0. The association between magnitude of proteinuria and development of uremic crises and death was determined before and after dogs with initial UP:C > or =1.0 were assigned to 3 subgroups and compared with dogs with initial UP:C < 1.0. Changes in reciprocal serum creatinine concentration were used to estimate decrease in renal function. RESULTS: Initially, dogs had similar clinical characteristics with the exception of systolic blood pressure and UP:C. Relative risks of development of uremic crises and death were approximately 3 times higher in dogs with UP:C > or =1.0, compared with dogs with UP:C < 1.0. Relative risk of adverse outcome was approximately 1.5 times higher for every 1-unit increment in UP:C. The decrease in renal function was of greater magnitude in dogs with UP:C > or =1.0, compared with dogs with UP:C < 1.0. CONCLUSIONS AND CLINICAL RELEVANCE: Initial UP:C > or =1.0 in dogs with CRF was associated with greater risk of development of uremic crises and death, compared with dogs with UP:C < 1.0. Initial determinations of UP:C in dogs with naturally occurring CRF may be of value in refining prognoses.

Frequency of urinary tract infection among dogs with pruritic disorders receiving long-term glucocorticoid treatment.

OBJECTIVE: To determine frequency of urinary tract infection (UTI) among dogs with pruritic disorders that were or were not receiving long-term glucocorticoid treatment. DESIGN: Observational study. ANIMALS: 127 dogs receiving glucocorticoids for > 6 months and 94 dogs not receiving glucocorticoids. PROCEDURE: Bacterial culture of urine samples was performed in dogs receiving long-term glucocorticoid treatment, and information was collected on drug administered, dosage, frequency of administration, duration of glucocorticoid treatment, and clinical signs of UTI. For dogs not receiving glucocorticoids, a single urine sample was submitted for bacterial culture. RESULTS: Multiple (2 to 6) urine samples were submitted for 70 of the 127 (55%) dogs receiving glucocorticoids; thus, 240 urine samples were analyzed. For 23 of the 127 (18.1%) dogs, results of bacterial culture were positive at least once, but none of the dogs had clinical signs of UTI. Pyuria and bacteriuria (present vs absent) were found to correctly predict results of bacterial culture for 89.9% and 95.8% of the samples, respectively. Type of glycocorticoid, dosage, frequency of administration, and duration of treatment were not associated with frequency of UTI. None of the urine samples from dogs not receiving glucocorticoids yielded bacterial growth. The frequency of UTI was significantly higher for dogs treated with glucocorticoids than for dogs that had not received glucocorticoids. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dogs receiving long-term glucocorticoid treatment have an increased risk of developing a UTI. On this basis, we recommend that urine samples be submitted for bacterial culture at least yearly for such dogs.

Clinical evaluation of dietary modification for treatment of spontaneous chronic renal failure in dogs.

OBJECTIVE: To determine whether a diet used for dogs with renal failure (renal food [RF]) was superior to an adult maintenance food (MF) in minimizing uremic crises and mortality rate in dogs with spontaneous chronic renal failure. DESIGN: Double-masked, randomized, controlled clinical trial. ANIMALS: 38 dogs with spontaneous chronic renal failure. PROCEDURE: Dogs were randomly assigned to a group fed adult MF or a group fed RF and evaluated for up to 24 months. The 2 groups were of similar clinical, biochemical, and hematologic status. The effects of diets on uremic crises and mortality rate were compared. Changes in renal function were evaluated by use of serial evaluation of serum creatinine concentrations and reciprocal of serum creatinine concentrations. RESULTS: Compared with the MF, the RF had a beneficial effect regarding uremic crises and mortality rate in dogs with mild and moderate renal failure. Dogs fed the RF had a slower decline in renal function, compared with dogs fed the MF. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary modifications are beneficial in minimizing extrarenal manifestations of uremia and mortality rate in dogs with mild and moderate spontaneous chronic renal failure. Results are consistent with the hypothesis that delay in development of uremic crises and associated mortality rate in dogs fed RF was associated, at least in part, with reduction in rate of progression of renal failure.

Association between initial systolic blood pressure and risk of developing a uremic crisis or of dying in dogs with chronic renal failure.

OBJECTIVE: To determine whether high systolic blood pressure (SBP) at the time of initial diagnosis of chronic renal failure in dogs was associated with increased risk of uremic crisis, risk of dying, or rate of decline in renal function. DESIGN: Prospective cohort study. ANIMALS: 45 dogs with spontaneous chronic renal failure. PROCEDURE: Dogs were assigned to 1 of 3 groups on the basis of initial SBP (high, intermediate, low); Kaplan-Meier and Cox proportional hazards methods were used to estimate the association between SBP and development of a uremic crisis and death. The reciprocal of serum creatinine concentration was used as an estimate of renal function. RESULTS: Dogs in the high SBP group were more likely to develop a uremic crisis and to die than were dogs in the other groups, and the risks of developing a uremic crisis and of dying increased significantly as SBP increased. A greater decrease in renal function was observed in dogs in the high SBP group. Retinopathy and hypertensive encephalopathy were detected in 3 of 14 dogs with SBP > or = 180 mm Hg. Systolic blood pressure remained high in 10 of 11 dogs treated with antihypertensive drugs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that initial high SBP in dogs with chronic renal failure was associated with increased risk of developing a uremic crisis and of dying. Further studies are required to determine whether there is a cause-and-effect relationship between high SBP and progressive renal injury and to identify the risks and benefits of antihypertensive drug treatment.

Risk factors associated with the development of chronic kidney disease in cats evaluated at primary care veterinary hospitals.

OBJECTIVE: To identify risk factors associated with diagnosis of chronic kidney disease (CKD) in cats. DESIGN: Retrospective case-control study. ANIMALS: 1,230 cats with a clinical diagnosis of CKD, serum creatinine concentration > 1.6 mg/dL, and urine specific gravity < 1.035 and 1,230 age-matched control cats. PROCEDURES: Data on putative risk factors for CKD were extracted for multivariate logistic regression analysis from the medical records of cats brought to 755 primary care veterinary hospitals. For a subset of cats evaluated 6 to 12 months prior to the date of CKD diagnosis or control group inclusion, the percentage change in body weight between those dates as well as clinical signs at the earlier date were analyzed for associations with CKD development. RESULTS: Risk factors for CKD in cats included thin body condition, prior periodontal disease or cystitis, anesthesia or documented dehydration in the preceding year, being a neutered male (vs spayed female), and living anywhere in the United States other than the northeast. The probability of CKD decreased with increasing body weight in nondehydrated cats, domestic shorthair breed, and prior diagnosis of diabetes mellitus and increased when vomiting, polyuria or polydipsia, appetite or energy loss, or halitosis was present at the time of diagnosis or control group inclusion but not when those signs were reported 6 to 12 months earlier. Median weight loss during the preceding 6 to 12 months was 10.8% and 2.1% in cats with and without CKD, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The probability of CKD diagnosis in cats was influenced by several variables; recent weight loss, particularly in combination with the other factors, warrants assessment of cats for CKD.

Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats.

OBJECTIVE: To provide a framework for successfully managing chronic kidney disease (CKD) over an extended period of time with the goal of optimizing clinical outcomes by fostering a veterinarian-client relationship that facilitates successful application of evidence-based treatment. ETIOLOGY: Ultimately, CKD results from loss of functional nephrons; however, the specific disease process responsible for this loss usually cannot be determined due to development of chronic changes (eg, fibrosis) and compensatory adaptations that have occurred in the kidneys of patients with CKD. Earlier diagnosis may foster a better understanding of the etiologies of CKD. DIAGNOSIS: Diagnosis of CKD is based on establishing loss of kidney function(s) due to primary kidney disease that have been present for an extended time (typically 3 months or longer). THERAPY: The goals of therapy are to: (1) slow progressive loss of kidney function, (2) ameliorate clinical and biochemical consequences of CKD, and (3) maintain adequate nutrition. These goals are achieved by: (1) managing adaptive processes that promote progression of CKD, (2) controlling intake of water, nutrients, minerals and electrolytes, and (3) correcting hormonal deficiencies. PROGNOSIS: The short-term prognosis for dogs with CKD varies from good to poor, while the long-term prognosis for dogs with CKD is generally guarded to poor depending on the International Renal Interest Society (IRIS) CKD stage of the patient. Both short-term and long-term prognosis for cats with CKD may vary from good to poor depending on the IRIS CKD stage. However, prognosis is more variable and unpredictable in cats.

Chronic kidney disease in small animals.

Chronic kidney disease (CKD) affects multiple body systems and presents with a wide variety of clinical manifestations. Proper application of conservative medical management can profoundly affect the clinical course of CKD. Diagnosis and management is facilitated by staging CKD and applying therapies that are appropriate for the patient's stage of CKD. Therapy and follow-up of CKD are described, with emphasis on stage-based therapy to ameliorate clinical signs and slow progression.