scholarly journals Familial nephropathy in Bracchi Italiani: 8 cases (2012–2019)

Author(s):  
Amanda L. Inman ◽  
Ashley E. Allen-Durrance ◽  
Rachel E. Cianciolo ◽  
Autumn N. Harris

Abstract OBJECTIVE To characterize the signalment, clinical signs, clinical pathological and histologic findings, and outcome in 8 related Bracchi Italiani with proteinuric kidney disease. ANIMALS 8 client-owned Bracchi Italiani. PROCEDURES Health records submitted to the Bracco Italiano Health Foundation and the Bracco Italiano Club of America between 2012 and 2019 were reviewed for dogs with evidence of nephropathy for which histologic diagnoses were obtained. Pedigree, signalment, clinical signs, diagnostic test results (including microscopic examination of kidney tissue samples collected ante- or postmortem), and outcome were acquired. Results were presented as descriptive statistics. RESULTS The most common clinical sign in affected dogs was inappetence. All dogs were proteinuric, and 4 dogs were azotemic. Seven dogs developed clinical signs of kidney disease and were euthanized a median of 75 days postdiagnosis. Six dogs had glomerular amyloidosis, and 1 dog each had nephrosclerosis and nonamyloidotic fibrillar glomerulopathy. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the clinical presentation may vary in affected dogs, and proteinuria in young or middle-aged Bracchi Italiani should raise the concern for hereditary nephropathy. Prognosis is likely poor once clinical signs are noted.

2013 ◽  
Vol 124 (12) ◽  
pp. 709-717 ◽  
Author(s):  
Chaodong Fang ◽  
Lei Shen ◽  
Liang Dong ◽  
Meng Liu ◽  
Sensen Shi ◽  
...  

Corin is a cardiac protease that regulates BP (blood pressure) by activating natriuretic peptides. Recent animal studies identified corin expression in the kidney where it may regulate renal function. In the present study, we tested the hypothesis that corin may be present in human urine and that urinary corin levels may be altered in patients with kidney disease. We obtained urine and kidney tissue samples from normal individuals and CKD (chronic kidney disease) patients. Using ELISA, we detected corin protein in human urine. In normal individuals, urinary corin levels did not correlate with that of plasma, indicating that urinary corin is probably of kidney origin. Compared with normal controls, CKD patients had markedly reduced urinary corin levels and this reduction correlated with disease severity. By immunostaining, human corin protein was identified on the epithelial cell surface in renal tubules. The renal corin mRNA and protein levels were significantly lower in CKD patients than non-CKD controls. The results indicate that renal tubular corin may be shed into urine and that urinary and renal corin levels were reduced in CKD patients. These data suggest that reduced corin levels in the kidney may reflect the underlying pathology in CKD.


2019 ◽  
Vol 56 (3) ◽  
pp. 465-475 ◽  
Author(s):  
Alicia Maclaine ◽  
María J. Forzán ◽  
Narges Mashkour ◽  
Jennifer Scott ◽  
Ellen Ariel

Juvenile eastern water dragons ( Intellagama lesueurii lesueurii) are highly susceptible to infection with Bohle iridovirus (BIV), a species of ranavirus first isolated from ornate burrowing frogs in Townsville, Australia. To investigate the progression of BIV infection in eastern water dragons, 11 captive-bred juveniles were orally inoculated with a dose of 104.33 TCID50 and euthanized at 3, 6, 8, 10, 12, and 14 days postinfection (dpi). Viral DNA was detected via polymerase chain reaction (PCR) in the liver, kidney, and cloacal swabs at 3 dpi. Mild lymphocytic infiltration was observed in the submucosa and mucosa of the tongue and liver at 3 dpi. Immunohistochemistry (IHC) first identified viral antigen in foci of splenic necrosis and in hepatocytes with intracytoplasmic inclusion or rare single-cell necrosis at 6 dpi. By 14 dpi, positive IHC labeling was found in association with lesions in multiple tissues. Selected tissues from an individual euthanized at 14 dpi were probed using in situ hybridization (ISH). The ISH labeling matched the location and pattern detected by IHC. The progression of BIV infection in eastern water dragons, based on lesion severity and virus detection, appears to start in the spleen, followed by the liver, then other organs such as the kidney, pancreas, oral mucosa, and skin. The early detection of ranaviral DNA in cloacal swabs and liver and kidney tissue samples suggests these to be a reliable source of diagnostic samples in the early stage of disease before the appearance of clinical signs, as well as throughout the infection.


2021 ◽  
Vol 12 ◽  
Author(s):  
Swastika Sur ◽  
Mark Nguyen ◽  
Patrick Boada ◽  
Tara K. Sigdel ◽  
Hans Sollinger ◽  
...  

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.


2020 ◽  
Vol 13 (S9) ◽  
Author(s):  
Hui Yu ◽  
Danqian Chen ◽  
Olufunmilola Oyebamiji ◽  
Ying-Yong Zhao ◽  
Yan Guo

Abstract Background Compared to the conventional differential expression approach, differential coexpression analysis represents a different yet complementary perspective into diseased transcriptomes. In particular, global loss of transcriptome correlation was previously observed in aging mice, and a most recent study found genetic and environmental perturbations on human subjects tended to cause universal attenuation of transcriptome coherence. While methodological progresses surrounding differential coexpression have helped with research on several human diseases, there has not been an investigation of coexpression disruptions in chronic kidney disease (CKD) yet. Methods RNA-seq was performed on total RNAs of kidney tissue samples from 140 CKD patients. A combination of differential coexpression methods were employed to analyze the transcriptome transition in CKD from the early, mild phase to the late, severe kidney damage phase. Results We discovered a global expression correlation attenuation in CKD progression, with pathway Regulation of nuclear SMAD2/3 signaling demonstrating the most remarkable intra-pathway correlation rewiring. Moreover, the pathway Signaling events mediated by focal adhesion kinase displayed significantly weakened crosstalk with seven pathways, including Regulation of nuclear SMAD2/3 signaling. Well-known relevant genes, such as ACTN4, were characterized with widespread correlation disassociation with partners from a wide array of signaling pathways. Conclusions Altogether, our analysis reported a global expression correlation attenuation within and between key signaling pathways in chronic kidney disease, and presented a list of vanishing hub genes and disrupted correlations within and between key signaling pathways, illuminating on the pathophysiological mechanisms of CKD progression.


2018 ◽  
Vol 315 (6) ◽  
pp. F1817-F1821 ◽  
Author(s):  
Robert A. Fenton

Biomarkers have the potential to greatly facilitate diagnosis and treatment of patients with various forms of kidney disease. State-of-the-art mass spectrometry-based methods possess the capability, on a proteome scale and in an unbiased manner, to detect alterations in protein abundances and/or posttranslational modifications in plasma, urine, or tissue. Such approaches can provide a large, unbiased database to facilitate identification of potential biomarkers. In the diagnosis of kidney diseases, urine is usually a more favorable specimen than plasma and kidney tissue due to its noninvasive collection and simplicity of processing. However, whether analysis of proteins in urine faithfully reflects their changes in the kidney tissue remains unclear. The use of proteomics to analyze kidney tissue samples collected during late-stage kidney diseases has also recently gathered pace. The goal of this minireview is to provide an overview of the proteomic technologies currently applied to studies of kidney and their limitations, present existing kidney and urine proteome databases, and highlight a few applications of such approaches in kidney disease biomarker discovery.


2018 ◽  
Vol 56 (1) ◽  
pp. 93-105 ◽  
Author(s):  
Sabrina D. Clark ◽  
Wenping Song ◽  
Rachel Cianciolo ◽  
George Lees ◽  
Mary Nabity ◽  
...  

MicroRNAs (miRNAs) are a group of small noncoding RNAs that act as regulators of posttranslational gene/protein expression and are known to play a key role in physiological and pathological processes. The objective of our study was to compare expression of miR-21 in renal tissue from dogs affected with chronic kidney disease (CKD) caused by X-linked hereditary nephropathy (XLHN), a disease equivalent to human Alport syndrome, to that from unaffected dogs. Additionally, we sought to characterize changes in relative mRNA expression of various genes associated with miR-21 function. miRNA was isolated from kidney tissue collected from both affected dogs and unaffected, age-matched littermates at defined milestones of disease progression, including end-stage renal disease (ESRD). Additionally, autopsy samples from affected dogs at ESRD and corresponding unaffected dogs were evaluated. Samples were scored based on histological changes, and relative expression of miR-21 and kidney disease-related genes was determined using quantitative real-time polymerase chain reaction. In affected dogs, significant upregulation of kidney miR-21 was first detected at the milestone corresponding with increased serum creatinine. Furthermore, miR-21 expression correlated significantly with urine protein: urine creatinine ratio, serum creatinine concentration, glomerular filtration rate, and histologic lesions (glomerular damage, tubular damage, chronic inflammation, and fibrosis). At end-stage disease, COL1A1, TGFB1 and its receptor, TGFB2, and Serpine1 were upregulated, while PPARA, PPARGC1A, ACADM, SOD1, and EGF were downregulated. In conclusion, miR-21 is abnormally upregulated in the kidneys of dogs with CKD caused by XLHN, which may play an important pathologic role in the progression of disease by dysregulating multiple pathways.


2020 ◽  
Author(s):  
Lin Yang ◽  
Tsun Kit Chu ◽  
Jinxiao Lian ◽  
Cheuk Wai Lo ◽  
Shi Zhao ◽  
...  

AbstractObjectivesThis study is aimed to develop and validate a prediction model for multi-state transitions across different stages of chronic kidney disease in patients with type 2 diabetes mellitus under primary care.SettingWe retrieved the anonymized electronic health records of a population based retrospective cohort in Hong Kong.ParticipantsA total of 26,197 patients were included in the analysis.Primary and secondary outcome measuresThe new-onset, progression, and regression of chronic kidney disease were defined by the transitions of four stages that were classified by combining glomerular filtration rate and urine albumin-to-creatinine ratio. We applied a multi-scale multi-state Poisson regression model to estimate the rates of the stage transitions by integrating the baseline demographic characteristics, routine laboratory test results and clinical data from electronic health records.ResultsDuring the mean follow-up time of 1.7 years, there were 2,935 patients newly diagnosed with chronic kidney disease, 1,443 progressed to the next stage and 1,971 regressed into an earlier stage. The models achieved the best performance in predicting the new-onset and progression with the predictors of sex, age, body mass index, systolic blood pressure, diastolic blood pressure, serum creatinine, HbA1c, total cholesterol, LDL, HDL, triglycerides and drug prescriptions.ConclusionsThis study demonstrated that individual risks of new-onset and progression of chronic kidney disease can be predicted from the routine physical and laboratory test results. The individualized prediction curves developed from this study could potentially be applied to routine clinical practices, to facilitate clinical decision making, risk communications with patients and early interventions.Article summaryStrengths of this studyEarly predictions for chronic kidney disease progression and timely intervention is critical for clinical management of patients with diabetes.We successfully developed a multi-scale multi-state Poisson regression models that achieved the satisfactory performance in predicting the new-onset and progression of chronic kidney diseases.The model incorporates the predictors of demographic characteristics, routine laboratory test results and clinical data from electronic health records.The individualized prediction curves could potentially be applied to facilitate clinical decision making, risk communications with patients and early interventions of CKD progression.Limitations of this studyThe cohort has a relatively short follow-up period and the retrospective study design might suffer from report bias and selection bias.


Author(s):  
Devasee Borakhatariya ◽  
A. B. Gadara

Oesophageal disorders are relatively uncommon in large animals. Oesophageal obstruction is the most frequently encountered clinical presentation in bovine and it may be intraluminal or extra luminal (Haven, 1990). Intraluminal obstruction or “choke” is the most common abnormality that usually occurs when foreign objects, large feedstuff, medicated boluses, trichobezoars, or oesophageal granuloma lodge in the lumen of the oesophagus. Oesophageal obstructions in bovine commonly occur at the pharynx, the cranial aspect of the cervical oesophagus, the thoracic inlet, or the base of the heart (Choudhary et al., 2010). Diagnosis of such problem depends on the history of eating particular foodstuff and clinical signs as bloat, tenesmus, retching, and salivation


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 460
Author(s):  
Tawni B. Riepe ◽  
Victoria Vincent ◽  
Vicki Milano ◽  
Eric R. Fetherman ◽  
Dana L. Winkelman

Efforts to advance fish health diagnostics have been highlighted in many studies to improve the detection of pathogens in aquaculture facilities and wild fish populations. Typically, the detection of a pathogen has required sacrificing fish; however, many hatcheries have valuable and sometimes irreplaceable broodstocks, and lethal sampling is undesirable. Therefore, the development of non-lethal detection methods is a high priority. The goal of our study was to compare non-lethal sampling methods with standardized lethal kidney tissue sampling that is used to detect Renibacterium salmoninarum infections in salmonids. We collected anal, buccal, and mucus swabs (non-lethal qPCR) and kidney tissue samples (lethal DFAT) from 72 adult brook trout (Salvelinus fontinalis) reared at the Colorado Parks and Wildlife Pitkin Brood Unit and tested each sample to assess R. salmoninarum infections. Standard kidney tissue detected R. salmoninarum 1.59 times more often than mucus swabs, compared to 10.43 and 13.16 times more often than buccal or anal swabs, respectively, indicating mucus swabs were the most effective and may be a useful non-lethal method. Our study highlights the potential of non-lethal mucus swabs to sample for R. salmoninarum and suggests future studies are needed to refine this technique for use in aquaculture facilities and wild populations of inland salmonids.


2021 ◽  
pp. 1098612X2110012
Author(s):  
Jade Renard ◽  
Mathieu R Faucher ◽  
Anaïs Combes ◽  
Didier Concordet ◽  
Brice S Reynolds

Objectives The aim of this study was to develop an algorithm capable of predicting short- and medium-term survival in cases of intrinsic acute-on-chronic kidney disease (ACKD) in cats. Methods The medical record database was searched to identify cats hospitalised for acute clinical signs and azotaemia of at least 48 h duration and diagnosed to have underlying chronic kidney disease based on ultrasonographic renal abnormalities or previously documented azotaemia. Cases with postrenal azotaemia, exposure to nephrotoxicants, feline infectious peritonitis or neoplasia were excluded. Clinical variables were combined in a clinical severity score (CSS). Clinicopathological and ultrasonographic variables were also collected. The following variables were tested as inputs in a machine learning system: age, body weight (BW), CSS, identification of small kidneys or nephroliths by ultrasonography, serum creatinine at 48 h (Crea48), spontaneous feeding at 48 h (SpF48) and aetiology. Outputs were outcomes at 7, 30, 90 and 180 days. The machine-learning system was trained to develop decision tree algorithms capable of predicting outputs from inputs. Finally, the diagnostic performance of the algorithms was calculated. Results Crea48 was the best predictor of survival at 7 days (threshold 1043 µmol/l, sensitivity 0.96, specificity 0.53), 30 days (threshold 566 µmol/l, sensitivity 0.70, specificity 0.89) and 90 days (threshold 566 µmol/l, sensitivity 0.76, specificity 0.80), with fewer cats still alive when their Crea48 was above these thresholds. A short decision tree, including age and Crea48, predicted the 180-day outcome best. When Crea48 was excluded from the analysis, the generated decision trees included CSS, age, BW, SpF48 and identification of small kidneys with an overall diagnostic performance similar to that using Crea48. Conclusions and relevance Crea48 helps predict short- and medium-term survival in cats with ACKD. Secondary variables that helped predict outcomes were age, CSS, BW, SpF48 and identification of small kidneys.


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