Urinary cystatin B differentiates progressive versus stable IRIS Stage 1 chronic kidney disease in dogs.

BACKGROUND: Early identification of dogs with progressive vs stable chronic kidney disease (CKD) might afford opportunity for interventions that would slow progression. However, currently no surrogate biomarker reliably predicts CKD progression. HYPOTHESIS/OBJECTIVES: Urinary cystatin B (uCysB), a novel kidney injury biomarker, predicts progressive disease in International Renal Interest Society (IRIS) CKD Stage 1. ANIMALS: Seventy-two dogs, including 20 dogs from 4 university centers with IRIS CKD Stage 1, with IDEXX symmetric dimethylarginine (SDMA) concentration up to 17 µg/dL and no systemic comorbidities, and 52 clinically healthy staff-owned dogs from a fifth university center. METHODS: A multicenter prospective longitudinal study was conducted between 2016 and 2021 to assess uCysB concentration in IRIS CKD Stage 1 and control dogs. Dogs were followed to a maximum of 3 years (control) or 25 months (CKD). Stage 1 IRIS CKD was classified as stable or progressive using the slope of 1/SDMA, calculated from 3 timepoints during the initial 90-day period. Dogs with slope above or below -0.0007 week × dL/µg were classified as stable or progressive, respectively. Mixed effects modeling was used to assess the association between uCysB and progression rate. RESULTS: Estimates of first visit uCysB results predictive of active ongoing kidney injury based on the mixed effects models were 17 ng/mL for control, 24 ng/mL for stable CKD, and 212 ng/mL for progressive CKD (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary cystatin B differentiated stable vs progressive IRIS CKD Stage 1. Identification of dogs with progressive CKD may provide an opportunity for clinicians to intervene early and slow progression rate.

Differentiation of stable kidney function versus progressive dysfunction in dogs.

BACKGROUND: Circulating creatinine and symmetric dimethylarginine (SDMA) are biomarkers of kidney function that have been used variously to define stable vs progressive chronic kidney disease (CKD). Slope monitoring of inverse biomarker values (creatinine-1 or SDMA-1 ) has shown promise, but quantitative criteria to distinguish stable vs progressive CKD using this approach are lacking. OBJECTIVE: Assessment of creatinine-1 and SDMA-1 slope cutoffs to distinguish stable vs progressive CKD. ANIMALS: One hundred ten clinically healthy university staff-owned dogs and 29 male colony dogs with progressive X-linked hereditary nephropathy (XLHN). METHODS: Retrospective analysis combining 2 prospective observational studies, 1 tracking kidney function biomarkers in healthy dogs (HDs) to a maximum of 3 years, and 1 tracking kidney function biomarkers in male colony dogs with progressive XLHN to a maximum of 1 year. The minimum slope of creatinine-1 or SDMA-1 as measured using the IDEXX SDMA test from HD was assigned as the slope cutoff for stable kidney function. RESULTS: The stable vs progressive slope cutoff was -0.0119 week × dL/mg for creatinine-1 and -0.0007 week × dL/µg for SDMA-1 . CONCLUSIONS AND CLINICAL IMPORTANCE: In the studied CKD population, progressive dysfunction can be distinguished from stable kidney function by using the slope of creatinine-1 or SDMA-1 . These criteria may serve to characterize CKD in other cohorts of dogs and to establish guidelines for degrees of progression rate in dogs with naturally occurring CKD.

A review of phosphorus homeostasis and the impact of different types and amounts of dietary phosphate on metabolism and renal health in cats.

Elevated concentrations of serum phosphate are linked with progression and increased case fatality rate in animals and humans with chronic kidney disease. Elevated concentrations of serum phosphate can be a risk factor for development of renal and cardiovascular diseases or osteoporosis in previously healthy people. In rodents, an excess intake of dietary phosphorus combined with an inverse dietary calcium : phosphorus ratio (<1 : 1) contributes to renal calcification. Renal injury also has occured in cats fed experimental diets supplemented with highly soluble phosphate salts, especially in diets with inverse calcium : phosphorus ratios. However, not all phosphorus sources contribute similarly to this effect. This review, which focuses on cats, summarizes the published evidence regarding phosphorus metabolism and homeostasis, including the relative impact of different dietary phosphorus sources, and their impact on the kidneys. No data currently shows that commercial cat foods induce renal injury. However, some diets contain high amounts of phosphorus relative to recommendations and some have inverse Ca : P ratios and so could increase the risk for development of kidney disease. While limiting the use of highly soluble phosphates appears to be important, there are insufficient data to support a specific upper limit for phosphate intake. This review also proposes areas where additional research is needed in order to strengthen conclusions and recommendations regarding dietary phosphorus for cats.

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.

Clinicopathologic and Microbiologic Findings Associated with Emphysematous Cystitis in 27 Dogs.

This is a retrospective case series of 27 dogs with emphysematous cystitis. Medical records from two veterinary teaching hospitals from 1992 to 2014 were reviewed. The aims of the study were to determine imaging findings, common underlying disease processes, and prevalent bacterial species and their antimicrobial susceptibility patterns in dogs with emphysematous cystitis. The most common lower urinary tract sign was hematuria. Gas was detected in the wall and lumen of the urinary bladder in 14 of 27 dogs (51.9%), in only the wall of the bladder in 9 of 27 dogs (33%), and in only the lumen of the bladder in 4 of 27 dogs (14.8%). Comorbid diseases were identified in all but one case. The most common comorbid disease processes were diabetes mellitus in 33% of dogs, neurologic disease in 26% of dogs, and adrenal disease in 19% of dogs. Bacterial isolates included Escherichia coli, Enterococcus spp., Klebsiella pneumoniae, Proteus mirabilis, Streptococcus spp., and Actinomyces spp. Enterococcus spp. were always isolated in mixed infections with gas-producing bacterial species. During the period of study, most isolates were predicted to be susceptible to beta-lactam drugs, but updated veterinary breakpoints suggest that fluoroquinolones or trimethoprim-sulfamethoxazole would be more appropriate choices for empiric therapy.

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.

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.

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).

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.

American association of feline practitioners. Senior care guidelines.

BACKGROUND: Cats are the most popular pet in the United States and much of Northern Europe. Although 78% of owners consider their cats to be family members, many cats, particularly seniors, do not receive appropriate preventive care. One of the main obstacles to owner compliance is the lack of a clear recommendation by the veterinary team. Guidelines can help veterinarians to minimize this obstacle, strengthen the human-pet-veterinary bond, and improve the quality of life of cats. GOALS: The goals of this article are to assist veterinarians to: Deliver consistent high-quality care to senior cats. Promote longevity and improve the quality of life of senior cats by: recognizing and controlling health risk factors; facilitating and promoting early detection of disease; improving or maintaining residual organ function; and delaying the progression of common conditions. Define aspects of screening, diagnosis, treatment and anesthesia of senior cats.

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.

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.

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.