Evaluation of the diagnostic value of the renal resistive index as a marker of the subclinical development of cardiorenal syndrome in MMVD dogs.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) in dogs inevitably causes renal dysfunction. These interactions are known as the cardiorenal syndrome (CRS). The main aims of the study were to evaluate whether renal resistive index (RRI) may be useful as a non-invasive marker in subclinical stage of kidney injury in dogs with MMVD and to compare RRI with SDMA and Cyst C. METHODS: Forty-four dogs were divided into two groups: control-15 healthy dogs and the heart group-29 dogs with MMVD (ACVIM class Cc). Study protocol included: anamnesis, clinical examination, electrocardiography, echocardiography, chest radiography, abdominal ultrasonography with measurements of the renal resistive index (RRI), urine, and blood analysis. RESULTS: The RRI in the heart group was significantly higher 0.725 ± 0.035 versus control group 0.665 ± 0.028 (p < 0.00085). The RRI cut-off point in dogs with stable chronic heart failure (CHF) under 8 years is 0.775, in older 0.64. RRI was similar in MMVD dogs treated with ACE-I + furosemide and dogs treated ACE-I + torasemide + pimobendan + spironolactone. There was no correlation between RRI and SDMA or Cyst C. CONCLUSION: RRI is more sensitive than creatinine, SDMA and Cyst C to reveal kidney injury in MMVD dogs class Cc younger than 8 years.

Evaluation of Tryptic Podocin Peptide in Urine Sediment Using LC-MS-MRM Method as a Potential Biomarker of Glomerular Injury in Dogs with Clinical Signs of Renal and Cardiac Disorders.

The early asymptomatic stage of glomerular injury is a diagnostic challenge in the course of renal and extra-renal disease, e.g., heart insufficiency. It was found that podocin, a podocyte-specific protein present in the urine, may serve as a biomarker in the diagnosis of glomerular disease in humans and animals including glomerulonephritis, glomerulosclerosis, amyloidosis, or nephropathy. Therefore, there is a need of development of the sensitive and straightforward method of urinary podocin identification. In this work, we report our extended research under the glomerular injury investigation in dogs by application of clinical examination and LC-MS-MRM method in the identification of canine podocin in urine samples. The LC-MS-MRM method is based on the identification of podocin tryptic peptide with the 218H-AAEILAATPAAVQLR-OH232 sequence. The model peptide was characterized by the highest ionization efficiency of all the proposed model podocin tryptic peptides in a canine urine sediment according to the LC-MS/MS analysis. The obtained results revealed the presence of the model peptide in 40.9% of dogs with MMVD (active glomerular injury secondary to heart disease = cardiorenal syndrome-CRS) and 33.3% dogs with chronic kidney disease. The potential applicability of the developed methodology in the analysis of podocin in canine urine sediments was confirmed.

Evaluation of serum neutrophil gelatinase-associated lipocalin as a novel biomarker of cardiorenal syndrome in dogs.

Worsening renal function and azotemia in patients with heart failure (HF) are strongly associated with disease severity and poor prognosis. Increasing interest in this correlation led to the description and classification of cardiorenal syndrome (CRS). We evaluated the role of neutrophil gelatinase-associated lipocalin (NGAL) in the early detection of CRS in dogs with HF. Ten healthy dogs and 31 dogs admitted with HF were included in our study. NGAL and troponin-I were measured on samples collected on the day of admission; creatinine was measured on admission and again on day 7. The CRS group was defined as subsequently developing renal azotemia. Of 31 dogs with HF, 20 were included in the HF group, and 11 were included in the CRS group. The admission NGAL concentrations of the CRS group were significantly higher than those of other groups ( p < 0.001). The severity of HF evaluation based on the modified New York Heart Association classification showed significant correlation with NGAL ( p < 0.001) and troponin-I ( p = 0.009) concentration. However, only serum NGAL concentration at admission was significantly associated with the development of CRS in dogs with HF ( p = 0.021). The admission serum NGAL ≥ 16.0 ng/mL (optimal cutoff value) had a sensitivity of 90.9% and specificity of 90.0% in predicting the development of CRS.

Cardiorenal Syndrome: Diagnosis and Management.

Cardiorenal syndrome (CRS) has not been well characterized in veterinary medicine, yet an accurate appreciation of the kidney and the cardiovascular system and their interactions may have practical clinical implications. A consensus for cardiovascular-renal axis disorders of dogs and cats was recently attempted. The outcome of patients with CRS is likely to improve with the increasing awareness and ability to identify and understand the pathophysiologic characteristics of CRS. The utilization of existing and emerging organ-specific biomarkers with greater sensitivities than conventional diagnostics forecast new opportunities to diagnose and manage cardiac disease.

Preliminary Investigation of Cardiovascular-Renal Disorders in Dogs with Chronic Mitral Valve Disease.

BACKGROUND: Veterinary literature lacks data about cardiovascular-renal disorders (CvRD) and cardiorenal-anemia syndrome (CRAS) in dogs. HYPOTHESIS: A direct correlation exists between ACVIM class and IRIS stage; chronic kidney disease (CKD) complicates chronic mitral valve disease (CMVD) more often than does anemia in dogs. ANIMALS: One hundred and fifty-eight client-owned dogs with CMVD. METHODS: Signalment, physical examination findings, electrocardiography, thoracic radiographs, echocardiography, and blood analysis were retrospectively evaluated to assess the prevalence of CKD and anemia in dogs with CMVD and to investigate the relationships among ACVIM class, IRIS stage, and survival. RESULTS: The prevalence of CKD and anemia in dogs with CMVD was significantly higher than in the general population of dogs. Dogs being treated for heart failure had a significantly higher prevalence of CKD than did dogs that had not received treatment. A statistically significant direct correlation was found between ACVIM class and IRIS stage. Severe heart disease, severe renal disease or both, furosemide administration, and advanced age at diagnosis of heart disease were associated with shorter survival time. Survival time of dogs affected by CvRD was statistically shorter than survival time of dogs affected by CMVD alone. CONCLUSION AND CLINICAL RELEVANCE: Chronic mitral valve disease is associated with increased prevalence of CKD and anemia in dogs. Treatment for medical management of heart failure may play a role in inducing CKD. Class of heart disease and IRIS stage were directly correlated. Cardiovascular-renal disorders decrease survival time compared to the only presence of CMVD alone, whereas anemia does not play a central role in worsening heart function.

Evidence of cardiac injury and arrhythmias in dogs with acute kidney injury.

OBJECTIVES: Cardiac involvement in the course of acute kidney injury is described in humans as cardiorenal syndrome type 3 but has received only limited attention in dogs. This study was designed to evaluate cardiac injury and dysfunction in acute kidney injury in dogs and its association with outcome. METHODS: This prospective cohort study enrolled 24 client-owned dogs with acute kidney injury. Cardiac disorders were evaluated with thoracic radiographs, echocardiography, 24-hour Holter monitoring and cardiac troponin I concentrations within 2 days of admission and 7 to 10 days later. RESULTS: Most dogs were diagnosed with leptospirosis (n=18, 75%) and presented with moderate-to-severe acute kidney injury, International Renal Interest Society grades III to V. Dogs with ê100 ventricular premature complexes per 24 hour in the first examination (n=8) had significantly higher initial cTnI concentrations (P=0·007) compared to dogs with fewer than 100. In receiver operating characteristic curve analysis, the number of ventricular premature complexes was predictive of outcome (AUC 0·83, P<0·001). CLINICAL SIGNIFICANCE: Acute kidney injury seems to be associated with cardiac injury and arrhythmias in dogs. The data do not indicate a cardiac cause of poor outcome in dogs with increased number of ventricular premature complexes but the association may reflect the severity of disease.

Characterization of a Cardiorenal-like Syndrome in Aged Chimpanzees (Pan troglodytes).

Cardiorenal syndrome involves disease and dysfunction of the heart that leads to progressive renal dysfunction. This study investigated the relationship between cardiac and renal disease in 91 aged chimpanzees at the Alamogordo Primate Facility by evaluation of the medical histories, metabolic parameters, functional measurements of the cardiovascular system, clinical pathology, and histopathology focused on the heart and kidney. Cardiac fibrosis was the most frequent microscopic finding in 82 of 91 animals (90%), followed by glomerulosclerosis with tubulointerstitial fibrosis in 63 of 91 (69%). Cardiac fibrosis with attendant glomerulosclerosis and tubulointerstitial fibrosis was observed in 58 of 91 animals (63%); there was a statistically significant association between the 2 conditions. As the severity of cardiac fibrosis increased, there was corresponding increase in severity of glomerulosclerosis with tubulointerstitial fibrosis. Altered metabolic, cardiovascular, and clinical pathology parameters indicative of heart and kidney failure were commonly associated with the moderate to severe microscopic changes, and concurrent heart and kidney failure were considered the cause of death. The constellation of findings in the chimpanzees were similar to cardiorenal syndrome in humans.

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.