Efficacy of domperidone plus renal diet in slowing the progression of chronic kidney disease in dogs with leishmaniosis.

BACKGROUND: Chronic kidney disease (CKD) represents the main cause of mortality in dogs with leishmaniosis. Domperidone has recently been reported to improve kidney function in leishmaniotic dogs affected by CKD. Serum symmetric dimethylarginine (sSDMA) has also been shown to be a useful biomarker for earlier detection of decreased kidney function when compared to serum creatinine (sCr). This study aimed to assess the efficacy of domperidone plus renal diet in slowing the progression of nephropathy in leishmaniotic dogs with CKD, evaluating sSDMA and sCr as markers of kidney function. METHODS: This study was a therapeutic, prospective, randomized, controlled, 11-month-long field trial. Dogs were recruited if classified as "exposed" to or "infected" with Leishmania infantum and affected by CKD at early stages. After enrolment (T0), dogs were randomized into groups T (treatment) and C (control). All dogs were fed a renal diet and then followed up at 90 (T1), 210 (T2), and 330 (T3) days after inclusion in the study. At T1 and T2, dogs in group T received an oral suspension of domperidone (1 ml/10 kg once a day for up to 28 days). RESULTS: Twenty-two dogs (i.e., n = 12 in group T and n = 10 in group C) completed the study. At T0, the entire population of enrolled dogs presented a mean sSDMA value of 16.5 ± 3.4 µg/dl. At T1 (i.e., after 3 months of renal diet), sSDMA was significantly decreased in both groups, with an sSDMA of 13.1 ± 4.4 µg/dl for the entire population involved. From T1 to T3, sSDMA gradually increased in group C, while remaining stable in group T, which continued to show a significantly lower value of sSDMA at T3 than at T0. Regarding sCr, at T0 and T1, the mean values of the entire population of dogs were 1.1 ± 0.3 and 1.0 ± 0.4 mg/dl, respectively, with no statistical differences between groups T and C. In group T, sCr decreased significantly from T0 to T1, while returning at T3 to values similar to T0. CONCLUSIONS: In this study, domperidone plus renal diet reduced the progression of kidney disease in leishmaniotic dogs affected by CKD.

The knowns and unknowns of the efficacy of neem oil (Azadirachta indica) used as a preventative measure against Leishmania sand fly vectors (Phlebotomus genus).

Since domestic dogs are the main reservoir hosts of Leishmania infantum throughout the world, they are the main focus in terms of controlling zoonotic visceral leishmaniosis. To protect dogs from leishmaniosis, chemical repellents of durable efficacy are available in the form of collars, spot-on and sprays. However, the negative effects of chemical pesticides on the environment are well established as they affect animals and plants. This phenomenon has created the need for safer and more environmentally friendly substitutes. Plant extract-based insecticides and/or repellents have therefore been increasingly used by pet owners and veterinarians. Several botanical products have been tested as insecticides and/or repellents against a variety of bloodsucking arthropods that transmit human diseases. Among the products tested against Leishmania vectors, neem oil containing azadirachtin is the most studied. This study reviews the scientific literature concerning the efficacy of neem oil (azadirachtin-based products) against phlebotomine sand fly bites. A questionnaire was also administered to assess Italian veterinarians' attitudes to the use of neem oil. The survey was anonymous and consisted of three closed-ended questions. According to the data reported in the literature, the efficacy of neem oil in reducing the risk of sand fly bites has been tested against Phlebotomus papatasi, Phlebotomus perniciosus, Phlebotomus argentipes, Phlebotomus orientalis and Phlebotomus bergeroti. The efficacy of the products tested was expressed in percentages, ranging from 74.9% to 100%. The protection time was only available for six out of eight studies, ranging from "only during the first hour" (minimum protection time) to "all night" (expected maximum protection time). As regards the attitude to recommending the use of neem oil, 208 veterinarians participated in the online survey. Of the 126 veterinarians who recommended natural products, 119 (94.44%) reported that they recommended the use of neem oil-based products. Considering the limited data on the duration of protection and the dose of the active ingredient, more studies are required on the efficacy of neem oil-based products in reducing the risk of contracting canine leishmaniosis. These studies should also refer specifically to the concentration of the active ingredient as well as the interval of administration. Until such results are available, the use of azadirachtin-based products as the only topical products for the prevention of leishmaniosis in dogs is not recommended.

Clinical and Histopathological Features of Renal Maldevelopment in Boxer Dogs: A Retrospective Case Series (1999-2018).

Renal maldevelopment (RM) has been proposed to replace the old and sometimes misused term "renal dysplasia" in dogs. Although renal dysplasia has been described in Boxers, hereditary transmission has only been hypothesized. This study reports clinical and renal histological findings in Boxer dogs with RM, proposing a possible mode of inheritance. Medical records of 9 female Boxer dogs, older than 5 months and with a clinical diagnosis of chronic kidney disease prior to one year of age, were retrospectively reviewed. Polyuria and polydipsia (PU/PD), decreased appetite, weight loss, lethargy and weakness were described in all affected dogs. Common laboratory findings were proteinuria, diluted urine, non-regenerative anemia, azotemia, hyperphosphatemia, hypoalbuminemia and hypercholesterolemia. Histopathology of the kidneys revealed the presence of immature glomeruli in all dogs, which is consistent with RM. In 7 related dogs, the pedigree analysis showed that a simple autosomal recessive trait may be a possible mode of inheritance. Renal maldevelopment should be suspected in young Boxer dogs with a history of PU/PD, decreased appetite, weight loss, lethargy, weakness and proteinuria. Due to its possible inheritance, an early diagnosis of RM may allow clinicians to promptly identify other potentially affected dogs among the relatives of the diagnosed case.

Dirofilarioses in two cats in southern Italy.

Two cats infected by Dirofilaria immitis and Dirofilaria repens, respectively, were taken to two different private practitioners for a clinical examination. The analyses conducted on the first cat revealed a microfilaraemia due to D. repens of 66 mfs/mL by a modified Knott's test. No clinical signs of D. repens infection were observed in the cat. The animal was euthanised because of a lymphoma condition, and two adult females of D. repens were found in the subcutaneous tissue of the lumbar and left scapular regions at the post-mortem examination. The second cat showed severe abnormalities in the white blood cells, including eosinophil count. Microfilariae of D. immitis were detected in the blood smear, with an average length (n = 2) of 296.2 µm. These clinical cases represent the first reports of feline dirofilarioses in southern Italy and are indicative of a common occurrence of dirofilarial infection in the local canine population.

A molecular survey of vector-borne pathogens and haemoplasmas in owned cats across Italy.

BACKGROUND: Feline vector-borne pathogens (FeVBPs) have been increasingly investigated for their impact on cat health and their zoonotic potential. The aim of the present study was to assess the prevalence of FeVBPs and haemoplasmas in cats across Italy and to identify potential risk factors linked to their occurrence. METHODS: Blood samples from 958 owned cats living in the North (n = 556), Centre (n = 173) and South (n = 229) of Italy were tested for Babesia spp., Hepatozoon spp., Ehrlichia spp., Anaplasma spp. and filarioids by conventional PCR (cPCR) and for haemoplasmas and Bartonella spp. by SYBR green real-time PCR. Cats included in the study represent a sub-sample from a larger number of animals enrolled in a previous study, which were selected based on the geographical origin. Data on cats' positivity for Leishmania infantum, feline leukaemia virus (FeLV) and for feline immunodeficiency virus (FIV), available from the previous study, were included and examined. Potential risk factors for pathogen infection were assessed in relationship to categorical variables including sex, geographical origin, breed, neutering status and age of cats. RESULTS: Out of the 958 cats, 194 (20.2%) were positive for at least one of the tested pathogens, 89 (16%) from the North, 32 (18.5%) from the Centre and 73 (31.9%) from the South of Italy. A high prevalence of FeVBPs was detected in male cats (n = 125, 27.8%), living in the southern part of the country (n = 73, 31.9%), younger than 18 months of age (n = 24, 22.4%) and not neutered (n = 39; 27.5%). In particular, 24 cats (2.5%) tested PCR-positive for Bartonella spp., of which 1.6% for B. henselae and 0.9% for B. clarridgeiae. A total of 111 cats scored PCR-positive for haemoplasmas (11.6%), specifically "Candidatus Mycoplasma haemominutum" (n = 95, 9.9%), M. haemofelis (n = 14, 1.5%) and "Candidatus Mycoplasma turicensis" (n = 2, 0.2%). Moreover, 39, 31 and 8 cats were positive for FeLV (4.1%), L. infantum (3.2%) and FIV (0.8%), respectively. Co-infections were registered for 19 (9.8%) cats. CONCLUSIONS: These results confirm the occurrence of haemoplasmas and FeVBPs throughout Italy. Preventive measures to protect both animal and human health should be carried out also for owned cats, even if no health status of animals has been assessed in this study.

Laboratory tests for diagnosing and monitoring canine leishmaniasis.

Although several reviews on canine leishmaniasis have been published, none thoroughly described clinicopathologic abnormalities and their clinical usefulness. The aim of this review was to provide information concerning current diagnostic tests relevant for clinical pathologists and from a practical perspective. Specifically, in canine leishmaniasis, nonregenerative normocytic normochromic anemia, thrombocytopenia, or leukogram changes may be present. Clinical chemistry and urinalysis may indicate renal dysfunction (azotemia, decreased urine specific gravity, proteinuria) and an inflammatory/immune response (increased acute phase proteins [APP] or α2 - and/or γ-globulins). Although a potential gammopathy is usually polyclonal, it may also appear oligo- or monoclonal, especially in dogs coinfected by other vector-borne pathogens. When lesions are accessible to fine-needle aspiration (lymphoadenomegaly, nodular lesions, joint swelling), cytology is strongly advised, as the presence of Leishmania amastigotes in a pattern of pyogranulomatous inflammation or lymphoplasmacytic hyperplasia is diagnostic. If the cytologic pattern is inconclusive, the parasite should be identified by histology/immunohistochemistry or PCR on surgical biopsies. Alternatively, cytology and PCR may be performed on bone marrow samples where amastigotes, along with erythroid hypoplasia, myeloid hyperplasia, plasmacytosis, or secondary dysmyelopoiesis can be observed. Dogs with overt leishmaniasis generally have high antibody titers, while low titers predominate in immunologically resistant infected dogs or in exposed dogs with no parasite confirmation. Quantitative serology is recommended in clinically suspect dogs as high-titer antibodies titers may confirm the clinical diagnosis. In confirmed and treated dogs, renal function and inflammatory/immune response variables should be periodically monitored.

Variation of proteinuria in dogs with leishmaniasis treated with meglumine antimoniate and allopurinol: a retrospective study.

A retrospective study was performed using 53 client owned dogs with leishmaniasis to determine whether the degree of proteinuria, evaluated by the urine protein/creatinine ratio (UP/C), changes following treatment with meglumine antimoniate and allopurinol. Medical records of dogs with leishmaniasis in clinical stage C (according to the Canine Leishmaniasis Working Group staging system) and either proteinuric or borderline proteinuric (according to the International Renal Interest Society [IRIS] staging system) were reviewed. All dogs were treated with meglumine antimoniate and allopurinol for 4-8 wk. After treatment, UP/C, total protein, and total globulin significantly decreased and albumin and the albumin/globulin ratio (A/G) increased. After treatment, 7 of the 53 dogs (13.4%) became nonproteinuric following either a proteinuric or borderline proteinuric stage. Moreover, 12 of the 53 proteinuric dogs (22.6%) changed their stage to borderline proteinuric. The antileishmaniasis treatment with meglumine antimoniate in combination with allopurinol in dogs significantly reduced the degree of proteinuria in a short period of time. The results of the current study may be useful to the veterinary practitioner in the clinical management of canine leishmaniasis (CanL) in dogs with proteinuric chronic kidney disease.

Microdamage accumulation changes according to animal mass: an intraspecies investigation.

The fatigue life of a structure is also influenced by its size. Statistically, a bone from a large animal is expected to bear a higher risk of stress fracture if compared to the same bone from a small animal of the same species. This is not documented in the dog, where individuals can have a 40 times difference in body mass. We investigated the effect of body size on cortical bone microdamage accumulation, cortical microstructural organization (porosity, osteon area, and osteocyte lacunar density), and turnover in dogs with a wide body mass range. The aim was to understand and mathematically model how the bone tissue copes with the microdamage accumulation linked to body mass increase. Calcified transverse cortical sections of 18 canine radii of remarkably different size were examined by means of a standard bulk-staining technique and histomorphometric standard algorithms. Relationships between the investigated histomorphometric variables age, sex and mass were analyzed by general linear multivariate models and exponential equations. Type and location of microdamage and bone turnover were not influenced by body mass. Gender did not influence any parameter. Age influenced bone turnover and activation frequency. Microcrack density was influenced by bone mass. Bones had a similar microstructural organization within the same species regardless of the subject's dimension. Microdamage accumulation is inversely related to bone mass, whereas bone turnover is mass-invariant. We theorize a mass-related change in the bone fracture toughness targeted to reach an optimal unique dimensionless curve for fatigue life.

Comparison of urine protein-to-creatinine ratio in urine samples collected by cystocentesis versus free catch in dogs.

OBJECTIVE: To assess whether urine protein-to-creatinine (UPC) ratios determined in urine samples collected by cystocentesis versus those collected by free catch provide similar diagnostic information for dogs. DESIGN: Evaluation study. ANIMALS: 115 client-owned dogs evaluated because of various health problems requiring urinalysis or to screen for proteinuria in an area endemic for leishmaniasis. PROCEDURES: 230 paired urine samples, 1 collected by cystocentesis and 1 by free catch, were collected from the 115 dogs. The UPC ratio was determined in paired urine samples (n = 162) from 81 dogs with no indication of active inflammation according to urine sediment analysis. On the basis of the UPC ratio of urine sample collected by cystocentesis, dogs were classified as nonproteinuric (UPC ratio < 0.2), borderline proteinuric (UPC ratio of 0.2 to 0.5), or proteinuric (UPC ratio > 0.5), according to the International Renal Interest Society (IRIS). RESULTS: The correlation between UPC ratio in urine samples collected by cystocentesis and by free catch was strong (r(2) = 0.90); 75 of 81 (92.6%) dogs had UPC ratios from both urine samples that resulted in classification in the same IRIS substage with a kappa coefficient of 0.83. CONCLUSIONS AND CLINICAL RELEVANCE: The UPC ratio in dogs was minimally affected in urine samples collected by free catch, thus allowing correct grading of proteinuria with this method. The high reliability of the UPC ratio in free-catch urine samples coupled with the ease of collection should increase the use of this value for assessment of proteinuria.

Ultrasound-assisted drainage and alcoholization of hepatic and renal cysts: 22 cases.

Twenty-two dogs and cats with symptomatic renal or hepatic cysts that had undergone ultrasound-assisted drainage and alcoholization were retrospectively evaluated. Common presenting complaints were anorexia, reluctance to move, and vomiting. Abdominal pain was observed in all cases. Systemic hypertension was identified in four dogs and four cats with renal cysts. Cyst drainage and alcoholization were achieved without complications in 19 animals, and all clinical signs resolved after the procedure. In three cases, transient bleeding was observed during alcoholization, and the procedure was interrupted. Blood pressure normalized in the four dogs with renal cysts, but it remained elevated in the four cats.

Diagnostic value of cytologic examination of gastrointestinal tract tumors in dogs and cats: 83 cases (2001-2004).

OBJECTIVE: To determine results of cytologic examination of fine-needle aspirates and impression smears of gastrointestinal tract tumors in dogs and cats. DESIGN: Retrospective case series. ANIMALS: 38 dogs and 44 cats with histologically confirmed gastrointestinal tract tumors. PROCEDURES: Results of cytologic examination of fine-needle aspirates (n = 67) or impression smears (31) were compared with the histologic diagnosis, and extent of agreement was classified as complete, partial, none, or undetermined. RESULTS: For 48 of the 67 (72%) fine-needle aspirates, there was complete or partial agreement between the cytologic and histologic diagnoses. For 12 (18%) aspirates, the extent of agreement could not be determined because the cytologic specimen was considered unsatisfactory. For 29 of the 31 (94%) impression smears, there was complete agreement between the cytologic and histologic diagnoses, and for 2 (6%), there was partial agreement. None of the impression smears were considered unsatisfactory. Proportion of samples with complete agreement and proportion of samples with complete or partial agreement were significantly higher for impression smears than for fine-needle aspirates. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that there was moderate agreement between results of cytologic examination of fine-needle aspirates from dogs and cats with gastrointestinal tract neoplasia and the definitive histologic diagnosis. The agreement between results of cytologic examination of impression smears and the histologic diagnosis appeared to be higher.

Proximal ureteral ectopia causing hydronephrosis in a kitten.

A 2-month-old, female cat was presented for abdomen dilation. The patient was undernourished, and severe left hydronephrosis was diagnosed after clinical, ultrasonographical and radiographical examination. Although pyelography was performed in order to visualise the ureteral course, surgery was necessary to reach a final aetiological diagnosis and treatment. At gross examination, the left ureter crossed the renal capsula at the level of the caudal renal pole, and the subcapsular ureteral segment was markedly dilated. Distal to the renal capsula, the left ureter was very thin when compared to the right. The parenchyma of the left kidney, as suggested by ultrasonographical evaluation, was extremely reduced in thickness. An ureteronephrectomy was performed. Histopathological evaluation revealed glomerular sclerosis and diffuse parenchymal fibrosis. Severe hydronephrosis derived from an altered renal pelvic anatomy and abnormal ureteral course determining functional stenosis. Diagnosis of congenital anomaly before development of complications such as hydronephrosis could have allowed a surgical renal capsulectomy and obstruction relief. To the author's knowledge, this is the first report of severe hydronephrosis associated to altered renal pelvic anatomy and proximal ureteral ectopia in cat.

Comparison of glomerular number and specimen length obtained from 100 dogs via percutaneous echo-assisted renal biopsy using two different needles.

Our objective was to evaluate possible differences in the number of glomeruli and length of renal biopsies collected in canine subjects by two different types of biopsy needles: a semiautomatic 18-gauge Trucut and an automated 18-gauge Jamshidi modified (Biopince). One hundred biopsy samples obtained from dogs of different ages and gender affected by different nephropathies were evaluated retrospectively. All animals were biopsied using one of the two different needles. Biopsies were performed under ultrasound guidance and evaluated by a single pathologist. Statistical analysis was performed to evaluate possible differences in the number of glomeruli and length of renal biopsies collected comparisons were determined between subgroups of dogs with or without the identification of renal interstitial infiltrates and/or fibrosis. Neither the mean difference of the number of glomeruli nor the length of tissue sample collected with the different needles was significantly different. Likewise, the average biopsy length did not differ in dogs with or without renal interstitial infiltrate in animals biopsied with either biopsy needle. Both the Biopince and the Trucut devices provide diagnostically adequate biopsy renal specimens using ultrasound-guidance.

Free light-chain proteinuria and normal renal histopathology and function in 11 dogs exposed to Lleishmania infantum, Ehrlichia canis, and Bbabesia canis.

The purpose of this retrospective study was to investigate the relationship among proteinuria consisting of immunoglobulin free light chains (FLCs), renal histopathologic findings, and routine markers of renal function in 11 dogs exposed to Leishmania infantum (n = 8), Ehrlichia canis (n = 2), and Babesia canis (n = 1). FLC proteinuria was suspected based on identification of a 22- to 27-kDa band by sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and later confirmed by immunofixation electrophoresis. SDS-AGE identified an isolated band of 22-27 kDa in 8 dogs, whereas the remaining 3 had a 22- to 27-kDa band and an additional band of 67-72 kDa. The median urine protein-to-urine creatinine ratio was 0.37 (range, 0.11-2.24) and increased ratios were found in 6 dogs (54.5%) (reference value, <0.7). All dogs underwent histologic examination of renal percutaneous biopsy specimens and determination of serum creatinine and urea concentrations. Tissue samples for light microscopy were stained with hematoxylin-eosin, periodic acid-Schiff, Goldners trichrome, and methenamine silver. In the study group, the glomerular tufts, mesangium, tubulointerstitium, and vessels appeared unaffected. The median serum creatinine concentration in these 11 dogs was 1.3 mg/dL (range, 0.8-1.5 mg/dL; reference range, 0.6-1.5 mg/dL), whereas the concentration for urea was 28 mg/dL (range, 22-52 mg/dL; reference range, 20-50 mg/dL). All dogs had normal renal morphology and had normal serum creatinine and urea concentrations, suggesting that immunoglobulin FLC may be detected in the urine of dogs exposed to L. infantum, E. canis, and B. canis without any apparent structural or functional renal derangement.

Echo-assisted percutaneous renal biopsy in dogs. A retrospective study of 229 cases.

Renal biopsies were carried out on 229 dogs using an echo-assisted, semi-automatic method. Complications arising after the biopsy were also evaluated. The biopsies were examined for the accuracy of diagnosis and the presence of histologically demonstrable primary renal pathologies. A retrospective study of the observed lesions and parenchymal echogenicity showed a correlation between these factors involving the tubulo-interstitial compartment. Histopathological renal lesions and their correlation with laboratory methods are the only parameters that allow a correct diagnostic, prognostic, and therapeutic work-up in cases of clinical kidney disease in canines.

Glomerular lesions in dogs infected with Leishmania organisms.

OBJECTIVE: To histologically identify glomerular lesions in dogs infected with Leishmania organisms. ANIMALS: 41 dogs (17 sexually intact males and 14 sexually intact and 10 ovariohysterectomized females) that had positive results when tested for leishmaniosis as determined by use of serologic evaluation (indirect fluorescent antibody test, titers of 1:80 to 1:640) and direct microscopic identification of the protozoal organisms. PROCEDURE: Urine samples were collected by use of cystocentesis and examined by qualitative SDS-agarose gel electrophoresis (AGE). All dogs had non-selective (glomerular) or mixed (glomerular and tubular) proteinemia. Specimens were obtained from each dog during ultrasound-assisted renal biopsy and used for histologic examination. Each specimen was stained with H&E, periodic acid-Schiff, Goldner's trichrome, methenamine silver, and Congo Red stains. Specimens were adequate for evaluation when they contained at least 5 glomeruli/section, except for specimens stained with Congo Red in which 1 glomerulus/section was adequate. RESULTS: Examination of renal biopsy specimens revealed various glomerular lesions in all dogs and interstitial or tubular (or both) lesions in 23 of 41 (55%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Glomerular lesions that develop in dogs during infection with Leishmania organisms can be classified histologically as mesangial glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, and focal segmental glomerulonephritis. Tubulointerstitial histopathologic conditions were not observed as the primary lesion, despite being evident in 23 of 41 (55%) dogs. Use of SDS-AGE for qualitative evaluation of proteinuria and successive collection of specimens during renal biopsies following diagnosis of nonselective glomerular proteinuria provides the possibility for early identification of renal lesions.