Kidney Disease In Dogs Research Articles

Correlation of a quantitative and a semi-quantitative method for proteinuria detection in chronic kidney disease in dogs

Correlation of a quantitative and a semi-quantitative method for proteinuria detection in chronic kidney disease in dogs

Neutrophil Gelatinase-Associated Lipocalin (NGAL) Is Related with the Proteinuria Degree and the Microscopic Kidney Findings in Leishmania-Infected Dogs.

Early diagnosis of renal damage in Leishmania infected dogs may allow appropriate treatments and prevent some deaths. This study investigates neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of kidney disease in dogs experimentally infected with Leishmania infantum. Serum, urine, and kidney samples were collected from 30 infected beagle dogs and six uninfected control dogs. Based on proteinuria and azotemia values, dogs were initially classified. NGAL was measured in urine and serum samples. Then, the urinary NGAL to creatinine ratio (uNGAL/C) was calculated. Kidney samples were taken for histopathological studies, and the dogs were classified according to the severity of glomerular and tubulointerstitial lesions. In Leishmania-infected dogs, the uNGAL/C was significantly higher in proteinuric non-azotemic dogs compared with non-proteinuric non-azotemic dogs (p = 0.038). Serum NGAL (sNGAL) concentration did not differ between groups. Microscopic studies revealed several degrees of glomerulonephritis and slight focal lymphoplasmacytic interstitial nephritis in 89% and 55% of infected dogs, respectively. Urinary protein to creatinine ratio (UPC) and uNGAL/C were significantly higher in dogs with affected glomeruli compared to infected dogs without renal lesions (p = 0.045 and p = 0.043, respectively). The results show that uNGAL/C correlates with proteinuria and the presence of moderate glomerular lesions in non-azotemic dogs experimentally infected with L. infantum.

Uso do biomarcador renal dimetilarginina simétrica no diagnóstico precoce da insuficiência renal crônica em cães e gatos

A doença renal é comumente encontrada na clínica de pequenos animais, porém o seu diagnóstico é geralmente muito tardio. Pesquisas por biomarcadores renais mais sensíveis são foco de estudos, pois poderão proporcionar um diagnóstico precoce, permitir o estabelecimento da terapia adequada a cada paciente e melhorar a sua qualidade de vida. O biomarcador renal Dimetilarginina Simétrica (SDMA), tem apresentado resultados significativos em termos de precocidade para o diagnóstico da doença renal, podendo detectar lesão renal quando 50% da função está comprometida. O presente trabalho faz uma revisão da situação atual e perspectivas do emprego da dimetilarginina simétrica para estabelecimento do diagnóstico da doença renal em cães e gatos.

Acute on chronic kidney disease in dogs: Etiology, clinical and clinicopathologic findings, prognostic markers, and survival.

BackgroundChronic kidney disease (CKD) and acute exacerbation of CKD (ACKD) are common in dogs.ObjectiveTo characterize the etiology, clinical and laboratory findings, and short‐ and long‐term prognosis of dogs with ACKD.AnimalsOne hundred dogs with ACKD.MethodsMedical records of dogs diagnosed with ACKD admitted to a veterinary teaching hospital were retrospectively reviewed.ResultsThe most common clinical signs included anorexia (84%), lethargy (77%), vomiting (55%) and diarrhea (37%). Presumptive etiology included inflammatory causes (30%), pyelonephritis (15%), ischemic causes (7%), other (3%), or unknown (45%). Median hospitalization time was 5 days (range, 2‐29 days) and was significantly longer in survivors (6 days; range, 2‐29 days) compared with nonsurvivors (4 days; range, 2‐20 days; P < .001). Mortality rate was 35%. International Renal Interest Society (IRIS) acute kidney injury (AKI) grade at presentation was associated (P = .009) with short‐term survival, but presumptive etiology was not (P = .46). On multivariable analysis; respiratory rate (P = .01), creatine kinase (CK) activity (P = .005) and serum creatinine concentration (SCR; P = .04) at presentation were associated with short‐term outcome. Median survival time of dogs discharged was 105 days (95% confidence interval [CI], 25‐184), with 35 and 8 dogs surviving up to 6 and 12 months, respectively. Presumptive etiology (P = .16) and SCR (P = .59) at discharge were not predictors of long‐term survival.Conclusion and Clinical ImportanceShort‐term outcome of dogs with ACKD is comparable to those with AKI but long‐term prognosis is guarded. The IRIS AKI grade at presentation is a prognostic indicator of short‐term outcome.

Fibroblast growth factor-23 as an early marker of CKD-mineral bone disorder in dogs: preliminary investigation.

To examine the relationship between fibroblast growth factor-23 levels, chronic kidney disease severity and mineral metabolic disorders associated to chronic kidney disease in dogs. Fifteen control and 75 chronic kidney disease dogs were retrospectively included. Serum fibroblast growth factor-23 concentration and other phosphate metabolite parameters were compared between controls and each International Renal Interest Society stage. Multiple regression analysis was performed to determine the predictors of fibroblast growth factor-23. Serum fibroblast growth factor-23 concentrations were significantly higher in dogs with IRIS stages 2, 3 and 4 chronic kidney disease than those in dogs in control group and with stage 1 and increased along with the severity of chronic kidney disease. Compared with control dogs, serum intact parathyroid hormone significantly increased from stage 2 and serum phosphorus concentrations increased in dogs with stage 4. In dogs with stage 2, fibroblast growth factor-23 levels significantly increased in those with hyperphosphatemia compared with those with normophosphatemia. While eight of 26 (30.8%) dogs with stage 2 developed hyperparathyroidism (intact parathyroid hormone>8.5ng/L), 19 (73.1%) dogs with stage 2 had elevated fibroblast growth factor-23 levels above the reference range (>528 pg/mL). Log creatinine, log intact parathyroid hormone and log product of total calcium and phosphorus were independent predictors of log fibroblast growth factor-23. This preliminary study suggests that canine fibroblast growth factor-23 might be involved in mineral metabolic disorders associated to chronic kidney disease in dogs, and this factor could be potentially used as an early marker for this condition.

How Ultrasound Can Be Useful for Staging Chronic Kidney Disease in Dogs: Ultrasound Findings in 855 Cases.

In patients affected by chronic kidney disease (CKD), some ultrasonographic (US) abnormalities have been shown to correlate better than others with the progression of the disease. The aim of the study was to evaluate the prevalence of the most frequent renal US abnormalities in dogs at different stages of CKD, and to investigate their association with CKD International Renal Interest Society (IRIS) stages. Medical records and ultrasonographical report of 855 dogs were retrospectively included. The most frequent renal ultrasonographic abnormalities were: increased cortical echogenicity, abnormal ratio of cortico-medullary junction (C/M) and pyelectasia. A statistically significant difference in the prevalence of irregular contour, abnormal cortico-medullary junction, abnormal C/M, increased cortical echogenicity, and pyelectasia was found for dogs at different IRIS stages. The number of dogs with more than one US abnormality increased significantly with the progression of IRIS stage. In conclusion, increased cortical echogenicity, abnormal C/M junction and pyelectasia were the most prevalent US abnormalities in our CKD population. Although none of the US abnormalities showed a significantly higher prevalence, the number of dogs presenting > 3 US abnormalities increased significantly from IRIS 2 to IRIS 4. Renal US is an excellent ancillary diagnostic test, which should be used together with renal functional parameters, to monitor the progression of CKD.

Serum symmetric dimethylarginine levels in a half-breed German shepherd dog with renal cystadenocarcinoma and nodular dermatofibrosis

This report describes the diagnosis, clinical signs, and laboratory and histopathological findings of a canine renal cystadenocarcinoma and nodular dermatofibrosis. A 10-year-old entire female half-breed German Shepherd Dog x Rottweiler was brought to a veterinary clinic with hematuria and was non-responsive to the treatment with ciprofloxacin and prednisone. Erythrogram showed a normocytic normochromic anemia. Serum biochemical analysis revealed mildly elevated aspartate aminotransferase activity and high level of symmetric dimethylarginine. Data acquired during physical examination, abdominal sonography and X-ray evaluation allowed for the presumptive diagnosis of renal cystadenocarcinoma and nodular dermatofibrosis, which was confirmed by kidney histopathology. Symmetric dimethylarginine serum level is useful with evaluating and staging of the chronic kidney disease in dogs affected by renal cystadenocarcinoma and nodular dermatofibrosis.

Association Between Exposure to Ehrlichia spp. and Risk of Developing Chronic Kidney Disease in Dogs.

Ehrlichiosis is a common vector-borne disease caused by Ehrlichia spp. This retrospective matched cohort study was performed to determine if dogs with Ehrlichia spp. antibodies had an increased incidence of chronic kidney disease (CKD). Exposure to Ehrlichia spp. was defined as having an Ehrlichia spp. antibody-positive result recorded at any point in their available patient history. The outcome of CKD was defined as concurrent increased symmetric dimethylarginine (>14 µg/dL) and creatinine (>1.5 mg/dL) for a minimum of 25 days with inappropriate urine specific gravity (<1.030). Patients were matched using propensity score matching to control for age, geography, and breed. A total of 22,440 patients and controls in E canis-endemic regions of the United States were used in this analysis. Contingency tables were used to compare dogs with and without exposure to Ehrlichia spp.-infected ticks and CKD outcome. The relative risk of CKD for patients exposed to ticks carrying Ehrlichia spp. was found to be 2.12 (95% confidence interval [1.35-3.15], p < 0.0006). This study identified that testing positive for Ehrlichia spp. antibodies in E canis-endemic regions is associated with higher incidence of CKD in dogs.

Clinical signs observed in different stages of chronic kidney disease in Dogs

Clinical signs observed in different stages of chronic kidney disease in Dogs

Ultrasonographic Changes in Stage II and Stage III of Chronic Kidney Disease in Dogs

Ultrasonographic Changes in Stage II and Stage III of Chronic Kidney Disease in Dogs

The Efficacy of Adipose-Derived Stem Cells (ADSCs) on Chronic Kidney Disease in Dogs

To investigate the therapeutic effect of adipose-derived stem cells (ADSCs) on chronic kidney disease (CKD) in dogs, blood routine examination, urine protein quantitative test, renal function test, urine sediment staining microscopy and B-ultrasonic test of kidney were used to compare the treatment of chronic kidney disease in dogs treated with three different therapies (NT treatment group: traditional supportive therapy group; MT1 treatment group: ADSCs treatment group; MT2 treatment group: NT mixed MT1 treatment group). Results showed that the numbers of red blood cells (RBC), hemoglobin (HGB) and hematocrit (HCT) in MT1 and MT2 treatment groups were higher than those in the NT group, and the urine protein excretion and the levels of serum urea and creatinine in MT1 and MT2 treatment groups were lower than those in the NT treatment group. Besides, there was no further deterioration of kidney morphology in MT1 and MT2 treatment groups. However, a large number of renal tubular epithelial cells and epithelial casts were observed in NT treatment group, while only a small number of renal tubular epithelial cells were observed in MT1 and MT2 treatment groups, indicating the intravenous injection of ADSCs can significantly improve the physical signs and renal function of dogs with CKD, and combined with the traditional therapy, ADSCs has a good prospect for the treatment of CKD in dogs.

Usefulness of UP/C Measurement for Kidney Disease in Dogs and Cats

Usefulness of UP/C Measurement for Kidney Disease in Dogs and Cats

Diagnostic potential of simplified methods for measuring glomerular filtration rate to detect chronic kidney disease in dogs.

BackgroundGlomerular filtration rate (GFR) is the most sensitive indicator of initial renal function decline during chronic kidney disease (CKD), but conventional protocols for measuring GFR are labor‐intensive and stressful for the dog.ObjectivesTo assess the diagnostic potential for detecting CKD with simplified GFR protocols based on iohexol plasma clearance.AnimalsSeventeen CKD‐positive and 23 CKD‐negative dogs of different breeds and sex.MethodsProspective nonrandomized study. Plasma iohexol was measured 5, 15, 60, 90, and 180 minutes after injection. Glomerular filtration rate was calculated using 5 samples (GFR5) or simplified protocols based on 1, 2, or 3 samples. The GFR5 and simplified GFR were compared by Bland‐Altmann and concordance correlation coefficient (CCC) analysis, and diagnostic accuracy for CKD by receiver operating characteristic curves. A gray zone for each protocol was bounded by the fourth quartile of the CKD‐positive population (lower cutoff) and the first quartile of the CKD‐negative population (upper cutoff).ResultsAll simplified protocols gave reliable GFR measurements, comparable to reference GFR5 (CCC >0.92). Simplified protocols which included the 180‐minutes sampling granted the best GFR measure (CCC: 0.98), with strong diagnostic potential for CKD (area under the receiver operating characteristic curve ± SE: 0.98 ± 0.01). A double cutoff including a zone of CKD uncertainty guaranteed reliable diagnosis outside the gray area and identified borderline dogs inside it.ConclusionsThe simplified GFR protocols offer an accurate, hands‐on tool for CKD diagnosis in dogs. The gray zone might help decision‐making in the management of early kidney dysfunction.

Urinary peptidome analyses for the diagnosis of chronic kidney disease in dogs

Chronic kidney disease (CKD) is clinically important in canine medicine. Current diagnostic tools lack sensitivity for detection of subclinical CKD. The aim of the present study was to evaluate urinary peptidome analysis for diagnosis of CKD in dogs. Capillary electrophoresis coupled to mass spectrometry analysis demonstrated presence of approximately 5400 peptides in dog urine. Comparison of urinary peptide abundance of dogs with and without CKD led to the identification of 133 differentially excreted peptides (adjusted P for each peptide <0.05). Sequence information was obtained for 35 of these peptides. This 35 peptide subset and the total group of 133 peptides were used to construct two predictive models of CKD which were subsequently validated by researchers masked to results in an independent cohort of 20 dogs.Both models diagnosed CKD with an area under the receiver operating characteristic (ROC) curve of 0.88 (95% confidence intervals [CI], 0.72–1.0). Most differentially excreted peptides represented fragments of collagen I, indicating possible association with fibrotic processes in CKD (similar to the equivalent human urinary peptide CKD model, CKD273). This first study of the urinary peptidome in dogs identified peptides that were associated with presence of CKD. Future studies are needed to validate the utility of this model for diagnosis and prediction of progression of canine CKD in a clinical setting.

Kidney disease in natural infection by Ehrlichia canis in dogs

Canine monocytic ehrlichiosis, caused by the intracellular bacterium Ehrlichia canis, can affect different organs, including the kidneys, in different stages of infection, and kidney involvement is considered one of the main causes of death related to the disease. This study aimed to investigate the occurrence of kidney disease in dogs naturally infected with E. canis and to correlate antibody levels with the severity of renal disease. Serum concentrations of urea, creatinine, and proteins (albumin and globulin), along with urine concentration, urine gamma-glutamyl transferase, and urine protein levels, were evaluated in 60 dogs with E. canis infection diagnosed by polymerase chain reaction. The detection of anti-E. canis antibodies was also performed for each dog. Of the 60 dogs with E. canis infection, 73.33% presented anti-E. canis antibodies. Laboratory abnormalities consistent with renal disease were observed in 33 (55%) infected dogs, and of these, 43.3% were in stage I chronic kidney disease. A positive correlation was observed between antibody levels and total plasma protein (p = 0.0332) and serum globulin (p = 0.0057) levels. In this study, renal disease was observed on routine laboratory testing in 55% of dogs with monocytic ehrlichiosis; however, there was no correlation between the stage of renal disease and the antibody titer against E. canis.

Relationships among urinary protein-to-creatinine ratio, urine specific gravity, and bacteriuria in canine urine samples.

BackgroundProteinuria is a marker of chronic kidney disease in dogs and a risk factor for increased morbidity and death. Predictive models using the results of readily available screening tests could foster early recognition.ObjectiveTo determine whether urine specific gravity (USG) and semiquantitative category of dipstick protein can be used to predict urinary protein‐to‐creatinine ratio (UP : C) and to examine the effect of urine culture results on UP : C in dogs.AnimalsThree hundred ninety‐four dogs (482 visits) presented to a university Community Practice Clinic or Veterinary Teaching Hospital between January 2011 and November 2015.MethodsRetrospective study. Medical records were searched to identify dogs for which urinalysis, UP : C measurement, and urine culture testing were performed during a single hospital visit. Urine specific gravity, UP : C, dipstick protein concentration, and findings of urine sediment analysis and urine culture were recorded. Regression or Spearman correlation analysis was used to test for relationships between UP : C and USG within dipstick categories and between UP : C and bacterial colony‐forming units per milliliter, respectively. Cohen's kappa test was used to evaluate agreement between urine culture and UP : C testing.ResultsThere were significant (P < .05) weak negative correlations (R2 range, 0.14‐0.37) between UP : C and USG for all nonnegative urine protein dipstick categories. The presence of a positive urine culture did not agree with the presence of abnormal UP : C (κ = −0.06).Conclusions and Clinical ImportanceWithin dipstick protein categories, UP : C cannot be accurately predicted from USG. Repeating UP : C measurement after resolution of urinary tract infection is advisable.

Urinary cystatin C as biomarker for identification of kidney disease in dogs

The aim of the study was to identify urinary biomarker for early detection of renal dysfunction in dogs. Paired blood and urine samples were analysed from dogs classified on the basis of International Renal Interest Society (IRIS) staging system. Serum biochemistry revealed a highly significant increase in blood urea nitrogen and creatinine levels in dogs with kidney disease. Urinalysis also revealed a highly significant increase in the level of urinary protein and urinary protein creatinine (UPC) ratio in dogs with kidney disease. A highly significant decrease in urinary creatinine and specific gravity level was also present in all groups of dogs with kidney disease. The SDS-PAGE of urinary proteins obtained from dogs with renal failure revealed the presence of low molecular weight (LMW) proteins of 14.7 KDa. This protein was identified as cystatin C protein by Immunoblotting using anti-cystatin C antibody and it has been suggested as biomarker for the diagnosis of renal disease.

Dietary therapy for chronic kidney disease in dogs and cats

Dietary therapy for chronic kidney disease in dogs and cats

Plasma indoxyl sulfate concentration predicts progression of chronic kidney disease in dogs and cats

Indoxyl sulfate is a protein-bound uremic toxin that increases as the severity of impaired renal function increases in humans, laboratory animals, dogs and cats. An elevation of indoxyl sulfate is related to prognosis among people with chronic kidney disease. However, whether indoxyl sulfate is able to predict the progression of chronic kidney disease in dogs and cats has not been previously studied. In the present study, 58 cats and 36 dogs with chronic kidney disease were enrolled. Plasma indoxyl sulfate was measured by high performance liquid chromatography. Renal progression was defined as an increase by one International Renal Interest Society (IRIS) stage and/or a rise in serum creatinine concentration of 0.5mg/dL during the same stage within a 3-month period.Compared with the non-progression groups, across different stages of renal failure, the baseline plasma indoxyl sulfate concentration was increased in the renal progression group (P<0.05), especially for IRIS stages 2 and 3 animals. The area under the receiver operator characteristic curves of indoxyl sulfate, when predicting renal progression, was above 0.75 for both dogs and cats. Indoxyl sulfate concentrations were also correlated with the increase of blood urea nitrogen, serum creatinine, and phosphate and the decrease of hematocrit among cats; while in dogs, concentrations were only correlated with the increase of phosphate concentrations. Indoxyl sulfate served as a biomarker of progression risk in dogs and cats with chronic kidney disease.

B-mode and Doppler ultrasound of chronic kidney disease in dogs and cats.

Ultrasound is the imaging test of choice for renal evaluation, because it provides information about the position, size, shape, internal architecture and hemodynamics of the kidneys without harming the patient. In chronic kidney disease, the main findings observed in B-mode ultrasound images are increased cortical echogenicity, loss of corticomedullary differentiation, reduced renal volume and irregular renal contour, and when these changes are associated, they are indicative of end-stage renal disease. However, the cause of kidney disease cannot be determined by ultrasonography, but must be confirmed by means of biopsy, although the presence of ultrasonographic changes indicative of the end-stage of the disease may contraindicate this procedure. The Doppler ultrasound test complements the ultrasonic B-mode examination and enables the assessment of renal perfusion based on a calculation of the hemodynamic indices, which are increased in cases of chronic kidney lesions, with higher values ​​in the most severe cases. Thus, ultrasound examinations are not only useful in diagnostics but also play an important role in defining the prognosis of patients with chronic kidney disease.