Proteomic research on new urinary biomarkers of renal disease in canine leishmaniosis: Survival and monitoring response to treatment.

The objective of our study was to search for survival biomarkers (SB) and treatment response monitoring biomarkers (TRMB) in the urinary proteome of dogs with renal disease secondary to canine leishmaniosis (CanL), using UHPLC-MS/MS. The proteomic data are available via ProteomeXchange with identifier PXD042578. Initially, a group of 12 dogs was evaluated and divided into survivors (SG; n = 6) and nonsurvivors (NSG; n = 6). A total of 972 proteins were obtained from the evaluated samples. Then, bioinformatic analysis reduced them to 6 proteins like potential SB increased in the NSG, specifically, Haemoglobin subunit Alpha 1, Complement Factor I, Complement C5, Fibrinogen beta chain (fragment), Peptidase S1 domain-containing protein, and Fibrinogen gamma chain. Afterwards, SG was used to search for TRMB, studying their urine at 0, 30, and 90 days, and 9 proteins that decreased after treatment were obtained: Apolipoprotein E, Cathepsin B, Cystatin B, Cystatin-C-like, Lysozyme, Monocyte differentiation CD14, Pancreatitis-associated precursor protein, Profilin, and Protein FAM3C. Finally, enrichment analysis provided information about the biological mechanisms in which these proteins are involved. In conclusion, this study provides 15 new candidate urinary biomarkers and an improved understanding of the pathogenesis of kidney disease in CanL.

Evaluation of heart fatty acid-binding protein as a biomarker for canine leishmaniosis.

BACKGROUND: Myocarditis frequently occurs in canine leishmaniosis (CanL). Heart fatty acid-binding protein (HFABP) is a biomarker of myocardial damage. METHODS: This study aimed to compare HFABP concentration (HFABPc) in healthy dogs and dogs at different stages of CanL and evaluate the correlation of this biomarker with several clinicopathological and echocardiographic variables. Thirty-one dogs diagnosed with CanL and 10 healthy dogs were included. RESULTS: HFABPc was not statistically different (p > 0.05) between groups of dogs at different LeishVet stages of CanL or between groups with high versus low to intermediate serology titres. In 70% of CanL dogs, HFABPc was within the 95% confidence interval limits of the mean of healthy dogs. A moderate negative correlation with globulin (r = -0.519; p = 0.03) and haematocrit (HCT) (r = -0.538; p = 0.02) was observed. No other significant correlation (p > 0.05) was observed with any other variable. LIMITATIONS: Many statistical tests were performed, and therefore, type I error cannot be ruled out. CONCLUSION: HFABPc is not consistently elevated in dogs with CanL and is not associated with the severity of the disease, or most echocardiographic or clinicopathological variables studied. The correlation with globulin and HCT was not strong and not considered clinically significant. HFABPc lacks sufficient predictive capacity in dogs with CanL, discouraging further research or clinical use of this biomarker in this disease.

Urinary proteome of dogs with renal disease secondary to leishmaniosis.

Canine leishmaniosis is frequently associated with the development of renal disease. Its pathogenesis is complex and not fully understood. For this reason, this study aimed to describe the urinary proteome, and identify possible new biomarkers in dogs with kidney disease secondary to leishmaniosis. Urine samples were collected from 20 dogs, 5 from healthy dogs, and 15 from stages Leishvet III and IV. Urine samples were analyzed by UHPLC-MS/MS. The data are available via ProteomeXchange with identifier PXD029165. A total of 951 proteins were obtained. After bioinformatic analysis, 93 urinary proteins were altered in the study group. Enrichment analysis performed on these proteins showed an overrepresentation of the complement activation pathway, among others. Finally, 12 discriminant variables were found in dogs with renal disease secondary to leishmaniosis, highlighting C4a anaphylatoxin, apolipoprotein A-I, haptoglobin, leucine-rich alpha-2-glycoprotein 1, and beta-2-microglobulin. This study is the first to describe the urinary proteomics of dogs with renal disease caused by leishmaniosis, and it provides new possible biomarkers for the diagnosis and monitoring of this disease.

Association of myocardial parasitic load with cardiac biomarkers and other selected variables in 10 dogs with advanced Canine Leishmaniasis.

BACKGROUND: The association between myocardial parasitic load (MPL) and cardiac biomarkers in Canine Leishmaniasis (CanL) has not been studied. METHODS: Dogs with advanced CanL were prospectively recruited and were included if they were euthanised. Prior to euthanasia these variables were assessed: hematocrit, globulin, creatinine, N-terminal-pro brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), blood pressure, urine protein/creatinine ratio and echocardiographic parameters. A left ventricular (LV) sample was taken for histopathology and MPL evaluation by quantitative PCR. Correlation of MPL with all variables was analysed. Dogs with lower and higher histopathology scores were compared. RESULTS: Ten dogs were included. NT-proBNP was 6946 pmol/ (interquartile range [IQR] 3751-9268 pmol/L) and cTnI 4.56 ng/mL (IQR 0.46-13.1 ng/mL). In all dogs, echocardiography showed an increase in LV thickening, and histopathology revealed moderate to severe lympho-plasmocytic myocarditis and/or myocardial cell degeneration. MPL was 215.53 parasites/gram (IQR 21.2-1372.63 parasites/gram). A strong correlation (p < 0.001; R = 0.90; R2 0.81) with cTnI was observed but correlation with any of the other variables or differences between the two histopathological scores, were not detected. CONCLUSIONS: MPL in dogs with advanced CanL shows variable but generally high levels. A strong association between MPL and cTnI was observed, which encourages the exploration of cTnI as a marker in CanL.

Comparison of N-terminal proB-type natriuretic peptide levels at different stages of visceral leishmaniosis and in patients with chronic kidney disease.

N-terminal proB-type natriuretic peptide (NT-proBNP) may be a useful marker in canine leishmaniosis (CanL). The aim was to compare NT-proBNP in dogs at different LeishVet stages of CanL and with idiopathic chronic kidney disease (CKD). Dogs diagnosed with CanL or CKD and a group of healthy dogs were included (group A, five normal dogs; group B, six dogs LeishVet 1-2; group C, 13 dogs LeishVet 3-4; group D, six dogs with CKD). NT-proBNP was higher (P<0.001) in group C (7.616 pmol/l, interquartile range (IQR) 3537-10,000 pmol/l) than in group A (293 pmol/l, IQR 257-373), group B (388.5 pmol/l, IQR 324-793) and group D (740 pmol/l, IQR 557-962 pmol/l). International Renal Interest Society (IRIS) kidney stage was not different between groups C and D or between groups A and B, but was different within all the rest of the group comparisons (P<0.001). In group C all dogs had echocardiographic increase in left ventricular mass index. NT-proBNP had negative correlation with haematocrit (P<0.001, r=0.749) and positive correlation with systemic blood pressure (P<0.001, r=0.728). NT-proBNP is consistently elevated in dogs with advanced CanL and is strongly correlated with the degree of systemic hypertension and anaemia. Moreover, dogs with advanced CanL exhibit increase in left ventricular mass. NT-proBNP may however be a less desirable cardiac marker as unlike cardiac troponin I it is often not elevated at earlier stages of CanL.

Imaging diagnosis-transcranial color-coded duplex sonography in a dog with hepatic encephalopathy.

We report the use of transcranial Doppler ultrasonography in a dog with hepatic encephalopathy secondary to a congenital portosystemic shunt. A severe increase in the pulsatility index was measured in the right middle cerebral artery, left middle cerebral artery, and basilar artery. These values returned to normal following medical stabilization of the patient and resolution of the neurologic signs. Transcranial Doppler ultrasonography appears to have value for monitoring the status of intracranial hypertension in patients with hepatic encephalopathy.

Assessing Circle of Willis blood circulation in dogs with transcranial color-coded duplex sonography.

Insonation of Circle of Willis by transcranial Doppler duplex color sonography is described in 30 healthy dogs with 15 weighing < 33 lb and 15 weighing >33 lb. Imaging was via a temporal window to explore the rostral, middle, and caudal cerebral arteries on both the left and right-hand sides; and through an suboccipital window to study the basilar artery. Normal mean values of the peak systolic velocity (PSV), end diastolic velocity, mean velocity, resistance index (RI), and pulsatility index (PI) were characterized and compared with those obtained in previous studies. There was significant differences in the PSV, RI, and PI in the rostral cerebral artery between dogs weighing < 33 vs. > 33 lb. Mean PSV was higher in weighing over 33 lb, whereas the mean resistive index and mean PI were lower in these dogs.