腹膜透析对庆大霉素诱导的犬急性肾损伤治疗作用研究

为了研究腹膜透析(peritoneal dialysis,PD)治疗和输液治疗对犬急性肾损伤(acute kidney injury,AKI)的疗效,试验对8只试验犬持续皮下注射硫酸庆大霉素注射液40～60 mg/(kg·d)11 d,通过监测血液肌酐(Cr)和尿素氮(BUN)等指标的变化建立犬AKI模型,检测血液Cr、BUN、白蛋白(ALB)、磷(P)、中性粒细胞明胶酶脂质运载蛋白(NGAL)和胱抑素C(Cys C)等指标,并对比采用腹膜透析治疗和输液治疗这两种方法进行治疗时的临床症状。结果表明:Cr浓度升高超出正常水平的50%,且BUN指标呈进行性升高说明造模成功;腹膜透析治疗时各项指标的恢复均比输液治疗迅速,其中BUN、NGAL和Cys C等指标在治疗3～5 d后就与输液治疗有明显差异;与输液治疗相比,腹膜透析治疗时犬只呕吐等临床症状消失更迅速,精神、食欲迅速好转。除血液Cr、BUN等传统指标外,NGAL与Cys C这2个指标在犬AKI诊断、治疗和监测中反应更加敏感,可作为犬AKI诊断和疗效的评价指标。说明在犬AKI治疗过程中腹膜透析治疗效果明显优于输液治疗。     

血清胱抑素C在犬急性肾损伤中的早期诊断意义

为了探讨血清胱抑素C(cystatin C,Cys-C)在犬急性肾损伤(AKI)中的早期诊断意义,将40只体重8~10 kg、年龄1~2岁的中华田园犬随机为对照组和试验组,连续7 d静脉注射0.9%生理盐水注射液200 m L,试验组额外添加90 mg/kg硫酸庆大霉素建立AKI模型,采集血液及尿液进行血清肌酐(CREA)、尿素氮(BUN)、Cys-C、尿比重、尿蛋白及尿沉渣的检查,并于造模第0、3、5、7、10天进行肾脏病理学检查。结果显示:对照组各项指标都未出现显著性差异(P0.05);试验组血清Cys-C浓度从造模第3天出现显著差异(P0.05),而血清中CREA和BUN分别自造模第6和7天出现显著差异(P0.05)。结果表明:血清CYs-C在犬AKI的诊断中比血清CREA、BUN更具有早期诊断意义。     

ornipural对犬急性肾衰竭的疗效观察

为了探讨ornipural对犬急性肾衰竭的临床疗效,试验对10只临床健康的犬肌肉注射50%甘油和庆大霉素(120 mg/kg)以人工制作急性肾衰竭模型,将发病犬分为对照组(用支持疗法)和试验组(在支持疗法的基础上静脉注射ornipural 5 mL/kg,治疗7 d),治疗期间监测尿量,分别在第3,7天检测血尿素氮、肌酐、磷酸根离子、钾离子指标;治疗后分别取各组犬的肾脏做病理组织切片,H.E.染色观察病理变化。结果表明:用ornipural治疗后犬的排尿量比对照组犬多,差异显著(P0.05);试验组有1只犬经过7 d治疗基本痊愈,且肌酐、磷酸根离子、钾离子都恢复到正常范围内,血尿素氮接近正常范围;对照组死亡犬的肾小球节段性硬化、肾小管堵塞。试验组犬第7天时肾小管通畅、肾小球结构恢复。说明ornipural对治疗犬急性肾衰竭有效。     

脂肪源间充质干细胞治疗犬急性肾衰竭的疗效观察

为了研究犬异体脂肪源间充质干细胞(Mesenchymal Stem Cell,MSC)移植对钩端螺旋体引起的急性肾衰竭(Acute renal failure,ARF)的治疗效果。采用Ⅰ型胶原酶消化法分离犬的脂肪MSC;通过静脉注射MSC对1例钩端螺旋体引起的急性肾衰竭犬进行治疗。结果显示,犬脂肪MSC呈长梭形、三角形或多菱形等形态、贴壁生长;干细胞移植治疗后一周,病犬精神恢复良好,饮食正常,检测血液肌酐和血磷含量下降至正常范围内,尿素氮含量明显下降且接近正常范围。表明犬脂肪MSC移植能有效治疗钩端螺旋体诱发的急性肾衰竭。     

一例犬急性肾衰竭的诊治体会

犬急性肾衰竭(Acuterenalfailure,ARF)近几年报道不断增加,为更好地了解ARF的临床特点及防治,文章通过对2014~2016年皖南地区宠物医院门诊诊断为ARF的50例病例资料进行分析,试图了解不同性别、年龄、品种同该病的关系,以及分析该病患犬的症状表现、发病原因、血液指标变化等情况,为该病的防治提供参考依据.     

50例犬急性肾衰竭的临床调查分析

犬急性肾衰竭(Acute renal failure,ARF)近几年报道不断增加,为更好地了解ARF的临床特点及防治,文章通过对2014~2016年怀化地区宠物医院门诊诊断为AR F的50例病例资料进行分析,试图了解不同性别、年龄、品种同该病的关系,以及分析该病患犬的症状表现、发病原因、血液指标变化等情况,为该病的防治提供参考依据。     

联苯双酯对犬急性肝损伤的保护作用

18只健康杂交犬随机平均分为3组(n=6):急性肝损伤对照组(简称对照组)、联苯双脂试验组(简称DDB组)和黄芪多糖试验组(简称黄芪组)。使用50%四氯化碳溶液(CCl4)造成犬急性肝损伤,对照组给予赋形剂(50mg/kg),DDB组给予DDB滴丸(50mg/kg),黄芪组给予黄芪多糖液(1mL/kg),每天1次,给药共7d。测定血清转氨酶和抗氧化能力指标,观察肝脏形态病理学改变。结果显示:DDB组犬血清转氨酶变化明显小于其他组;抗氧化指标变化明显好于对照组;肝组织切片中,肝细胞脂肪变性、炎细胞浸润均较对照组明显减轻,且肝组织中无明显纤维增生。结果表明:联苯双脂对CCl4造成的犬急性肝损伤有保护作用。     

犬冠状病毒感染的诊疗分析

犬冠状病毒病是由犬冠状病毒引起的一种犬的急性胃肠道传染病,传播迅速、致死率高,发病后呈不同程度的胃肠道炎症为特征。采用抗菌消炎、增强免疫力,输液防脱水、止吐止泻为治疗原则,将头孢曲松钠、利巴韦林注射液、注射用犬六联血清、注射用犬免疫球蛋白、犬干扰素等药物组成4个药物处方进行治疗。结果显示:单独使用抗菌消炎、输液防脱水的处方1药物组合,其治愈率为20%;以头孢曲松钠、利巴韦林注射液配合注射用犬六联血清、注射用犬免疫球蛋白和干扰素为组合的处方2治疗方案,其治愈率为85.7%,取得了良好的治疗结果,为该病的诊疗提供一定的参考。     

黄芪多糖与庆大霉素肌肉注射治疗犬脾虚泄泻证的比较

以犬为研究对象,探讨黄芪多糖注射液肌肉注射对犬脾虚泄泻证的临床治疗效果。24只健康本地犬饲养1周后灌胃番泻叶水煎剂人工复制脾虚泄泻证病理模型,造模成功后随机分为3组:黄芪多糖注射液治疗组肌肉注射黄芪多糖注射液0.25mL/kg,2次/d;庆大霉素组肌肉注射庆大霉素注射液0.2mL/kg,2次/d;病理对照组不作任何处理;同时设立4头健康犬作为空白对照,造模期间灌胃生理盐水。治愈后检测试验犬体质量、三大临床指标、白细胞、红细胞、血红蛋白及脾脏指数,并进行统计分析。结果表明,黄芪多糖注射液治疗组治愈后白细胞、血红蛋白、红细胞恢复较快,平均日增重及脾脏指数显著高于庆大霉素治疗组(P<0.05);三大临床指标各治疗组差异不显著(P>0.05)。说明黄芪多糖注射液可用于临床治疗动物脾虚泄泻证。     

肾衰竭患犬血清胱抑素C的表达及其对早期肾衰竭诊断价值的研究

为了研究血清胱抑素C(Cys C)在犬肾衰竭中的早期诊断价值,根据肌酐清除率将10例健康犬只作为正常对照组,将33例肾衰竭患犬分为肾功能代偿期组(11例)、肾功能失代偿期组(12例)、肾功能衰竭期组(6例)和尿毒症期组(4例),分别测定血清Cys C、肌酐(CRE)和尿素氮(BUN)的含量,并绘制肾功能代偿期组与正常对照组的受试者工作特征曲线(ROC曲线),以评价其对犬肾衰竭早期的价值。结果表明:肾功能代偿期组的血清Cys C明显高于正常对照组(P0.05),而CRE与BUN变化不明显(P0.05),其他三组的Cys C、CRE和BUN均极显著高于正常对照组(P0.01);血清Cys C的ROC曲线下面积为0.873,95%置信区间为0.752~0.994,P为0.004,截断值为0.98 mg/L,敏感度为90.4%,特异性为84.3%,约登指数为0.747。表明血清Cys C对犬肾衰竭的发生具有预测性,可作为犬肾衰竭早期诊断标志物。     

犬细小病毒单克隆抗体对犬细小病毒病的临床应用研究

采用犬细小病毒单克隆抗体（CPVMcAb）配合静脉注射用犬免疫球蛋白及静脉注射用犬血白蛋白,采用股内侧肌肉注射对172例细小病毒病患犬进行临床治疗试验。共治愈140例,治愈率为81．40％。采取以上治疗方案,结合对症支持治疗,发病1d的患犬治愈率90．70％,发病2d的患犬治愈率为85．29％,发病3d的患犬治愈率为56．25％,发病4d的患犬治愈卒为72．73％,发病5、d的患犬治愈率为77．78％。94．29％的治愈犬（132只）用药后4d内完全康复。采用该治疗方案,进入犬体内的McAb能迅速到达全身各组织,中和淋巴组织及血循环中的病毒,阻止病原复制和扩散;同时,中和反应形成抗原抗体复合物,可促进机体的主动免疫反应,促进患犬逐渐康复。该研究结果对提高犬细小病毒病的临床治疗效果具有积极的应用价值。     

Evaluation of adding diltiazem therapy to standard treatment of acute renal failure caused by leptospirosis: 18 dogs (1998–2001)

Objective: To assess efficacy and safety of intravenous (IV) diltiazem as a treatment for acute renal failure (ARF) secondary to leptospirosis in dogs. Design: Retrospective study Animals: Eighteen dogs with ARF caused by Leptospira spp treated during the months of September to December (1998–2001). Procedure: All dogs treated for ARF caused by Leptospira spp were enrolled in the study and were treated with standard care consisting of IV fluids, +/? furosemide, and antibiotics. With owner consent some dogs were treated with diltiazem at 0.1–0.5 mg/kg (0.045–0.22 mg/lb) IV slowly, followed by 1–5 μg/kg/minutes (0.45–2.2 mg/lb/minutes) constant rate infusion. Outcome measures were compared between the 2 groups (diltiazem versus standard). Diltiazem was administered within 60 hours of admission until serum creatinine fell into the normal range or stabilized. The primary outcome measurement of safety was systolic blood pressure (SBP). The primary measurement of efficacy outcome was the rate and magnitude of reduction of serum creatinine Results: Eleven out of 18 dogs received diltiazem. The rate of reduction in creatinine in the diltiazem group was 1.76 times faster than the standard group (P=0.054). Recovery of renal function showed a trend towards significant association with treatment group (exact P=0.08, odds ratio=3.62). This effect may be clinically relevant. Diltiazem had no clinically relevant effect on SBP. Conclusions and clinical relevance: Renal recovery in dogs with acute renal failure secondary to leptospirosis is improved with the administration of diltiazem in addition to ‘standard’ therapy.     

Expression and the molecular forms of neutrophil gelatinase‐associated lipocalin and matrix metalloproteinase 9 in canine mammary tumours

Neutrophil gelatinase‐associated lipocalin (NGAL) is a new biomarker for renal injury. It is also involved in tumorigenesis of different human cancer types. The oncogenic role of NGAL is related to its molecular forms, and heterodimer formation with matrix metalloproteinase 9 (MMP9) promotes human breast cancer (HBC) invasion and metastasis. To date, the levels of NGAL and NGAL/MMP9 complex have not yet been explored in canine mammary tumours (CMTs). Hence, this study aimed to investigate whether NGAL and its molecular forms could be the biomarker for CMT diagnosis. To this end, expression profile of NGAL and MMP9 in mammary epithelial cells as well as in urine samples were detected. By immunohistochemistry staining, NGAL was expressed at variable levels. Unlike HBC, a significant reduction in NGAL expression was demonstrated in benign and malignant CMTs as compared with normal controls. Additionally, NGAL expression was significantly reduced in dogs with metastatic CMTs. By contrast, the mean score of MMP9 expression in ascending order was normal groups, benign, and malignant CMTs. Interestingly, analysis of the molecular form revealed the NGAL/MMP9 complex presents in most mammary tissues and urine of dogs with benign or malignant CMTs, whereas the complex was absent in samples from dogs without CMTs. In conclusion, NGAL and MMP9 are ubiquitously expressed in canine mammary epithelial cells in normal and cancerous status. However, the NGAL/MMP9 complex exclusively presents in mammary tissues and urine of dogs with tumours.     

Metabolic and electrolyte disturbances in acute canine babesiosis.

Arterial blood pH, PCO2, bicarbonate, base excess/deficit, and lactate, as well as serum sodium, potassium, and chloride were measured in clinically normal dogs and in dogs with acute canine babesiosis. Metabolic acidosis developed in dogs with fatal as well as nonfatal Babesia canis infection. In the fatal group, the acidosis was uncompensated; among survivors, base deficit and blood lactate were significantly lower, and pH, PCO2, and bicarbonate values were significantly higher. Serum potassium values were significantly lower, and serum chloride values were significantly higher in dogs with acute babesiosis than in clinically normal dogs. The shock resulting from acute canine babesiosis is best viewed as anemic shock. Treatment should include an alkalizing agent, a blood transfusion, fluid therapy, and a babesicidal drug.     

QUANTITATIVE AND QUALITATIVE SCINTIGRAPHIC MEASUREMENT OF RENAL FUNCTION IN DOGS EXPOSED TO TOXIC DOSES OF GENTAMICIN

Five, 3-month-old mongrel dogs weighing between 4.5 to 5.5 kg were studied to evaluate and compare the efficiency of 99mTc-DTPA, 99mTc-MAG3, and 99mTc-DMSA in detecting gentamicin-induced renal tubular injury. After baseline renograms using all three methods, all dogs received daily intramuscular injections of gentamicin at a dose of 30-45 mg/kg. Additional studies were obtained after a cumulative dose of 450, 1,575, and 2,250 mg of gentamicin was reached. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and percentage of total renal uptake measurements were calculated. Baseline and post-gentamicin injection blood urea nitrogen (BUN) and serum creatinine values were determined. A Duncan test revealed significant renal function impairment at 450 mgs of cumulated gentamicin with 99mTc-DMSA and at 1,575 mgs of cumulated gentamicin for 99mTc-DTPA and 99mTc-MAG3. There was no correlation between BUN and serum creatinine values when compared to gentamicin (p > 0.05). The images obtained with 99mTc-MAG3 were of better quality than those obtained with 99mTc-DTPA even under severe renal dysfunction. Percentage of 99mTc-DMSA uptake indicated renal damage, before than GFR and ERPF. BUN and serum creatinine measurements were poor indicators of gentamicin-induced renal failure.     

犬慢性肾衰竭进程中肠道菌群代谢物短链脂肪酸水平的变化及其对肾功能的影响

本研究旨在评估短链脂肪酸在慢性肾衰竭患犬和健康犬中的水平,探究短链脂肪酸变化的原因及其对肾功能的影响。选取22例轻度慢性肾衰患犬（M-CRF组）、29例重度慢性肾衰患犬（S-CRF组）和26例健康对照犬（HC组）,用16S rDNA测序技术分析肠道菌群多样性,气相色谱法检测粪中短链脂肪酸浓度。通过粪菌移植和补充丁酸钠给5/6肾摘除犬,观察肠道菌群及丁酸钠对肾功能影响。结果显示：1）S-CRF组肠道菌群多样性指标观察物种数及Simpson指数低于HC组（P<0.05）,PCoA分析显示,S-CRF组肠道菌群与M-CRF、HC组有差异。2）LEfSe分析显示,S-CRF组和HC组间大量差异菌群,拟杆菌科、拟杆菌属及假单胞菌科等7个菌种富集于S-CRF组,普氏杆菌科、梭菌科、普氏杆菌属及普拉梭菌属等11个菌种富集于HC组。CCA分析发现富集于S-CRF组菌种丰度与肾功能指标呈正相关。3）S-CRF组粪中乙酸、丙酸及丁酸浓度均显著低于HC组和M-CRF组,M-CRF组丁酸浓度显著低于HC组（P<0.05）,且丁酸浓度与血中胱抑素C（Cys-c）、肌酐（Cr）及尿素氮（BUN）等肾功能指标呈负相关（r值分别为-0.451、-0.583和-0.514,P<0.01）。4）与慢性肾衰模型组（5/6 Nx组）比较,慢性肾衰犬给与丁酸钠8周后,血清Cr和BUN显著降低（P<0.05）;粪菌移植8周后,血清Cr和BUN显著升高（P<0.05）,丁酸钠可回调血清Cr和BUN水平。综上表明,慢性肾衰竭患犬肠道菌群多样性降低,菌群结构及丰度改变,粪中短链脂肪酸浓度降低,这些变化可加剧肾功能障碍。为犬慢性肾衰竭的防治提供新的理论依据。     

Preliminary evaluation of a particle-enhanced turbidimetric immunoassay (PETIA) for the determination of serum cystatin C-like immunoreactivity in dogs

Abstract: Serum cystatin C often is used in humans as a rapid and more sensitive marker than serum creatinine for glomerular filtration rate. The purpose of the present study was to evaluate whether cystatin C-like immunoreactivity (CLI) could be measured reliably in canine serum and to investigate whether dogs with clinical renal insufficiency had higher CLI levels than did clinically healthy dogs and dogs with nonrenal diseases. A commercially available particle-enhanced turbidimetric immunoassay (PETIA) for human serum cystatin C was used to measure canine serum CLI in a linear and proportional manner, with a mean recovery of 104%± 7.5% and coefficients of variation of 1.7 to 9.6%. The assay was then applied to serum samples from 17 clinically healthy dogs, 12 dogs with nonrenal diseases, and 8 dogs with renal insufficiency. Serum CLI was significantly higher in dogs with renal insufficiency (median serum CLI = 5.01 mg/L) than in clinically healthy dogs and dogs with nonrenal diseases (median serum CLI = 1.06 mg/L and 1.62 mg/L, respectively). Thus, canine serum CLI could be reliably measured using a commercially available PETIA designed for human serum cystatin C, and dogs with clinical renal insufficiency had, as expected, significantly higher serum CLI levels.     

Validation of a species-optimized enzyme-linked immunosorbent assay for determination of serum concentrations of insulin in dogs

Background: Measurement of canine serum insulin has relied on methods developed to measure human insulin. A species‐optimized test for measurement of serum insulin in dogs is now commercially available. Objective: The purpose of this study was to validate the canine ELISA for determination of serum insulin concentration in dogs. Methods: Precision was determined by evaluating intra‐ and interassay coefficient of variation (CV), and accuracy was determined by dilution and spike recovery studies. A method comparison study with samples from 34 clinically healthy dogs and 73 dogs examined for various illnesses and disorders (“patients”) was performed using the canine ELISA and an ELISA for human insulin. Biologic relevance of the canine assay was evaluated by measuring insulin in samples collected from 8 healthy dogs after administration of glucagon. A stability study was preformed with 6 samples stored at 20°C, 4–8°C, and ?20°C. Results: For the canine ELISA, intra‐ and interassay CVs were 4.3–7.8% and 4.4–7.7%, respectively. Mean recovery after dilution was 99% and recovery after spiking with porcine insulin was 116%. The canine and human ELISAs correlated well (r²=.94 for healthy dogs, r²=.88 for patient samples). After glucagon injection serum insulin concentrations increased significantly in 8 dogs. Insulin was stable for 30 days in 6 serum samples stored at ?20°C and in most samples for 8 days at 4–8°C. Insulin was stable for <3 days at room temperature (20°C). Conclusions: The new canine serum insulin ELISA had good precision and accuracy and correlated well with the previously used assay.     

In vivo cell tracking of canine allogenic mesenchymal stem cells administration via renal arterial catheterization and physiopathological effects on the kidney in two healthy dogs

Stem cell therapy is being special premise for various renal diseases. However, there is limited literature on localization and pathologic and functional effects of allogenic mesenchymal stem cells (MSCs) in healthy dogs. Two healthy dogs were included in this study. Canine MSCs (cMSCs) were cultured from canine bone marrow and incubated with superparamagnetic iron oxide (SPIO) for in vivo cell tracking via MR imaging. The dogs were given the MSC (3 × 10(6) cells) into a renal artery via femoral artery catheterization. Follow-up serial renal assessments included ultrasonography and MRI, serum chemistry, urine analysis, and renal clearance tests. The dogs were euthanized at days 8 and 35 respectively for histopathologic evaluation of kidney. Strong hypointensity in MRI was detected in the treated renal cortex the day after cMSCs infusion. However they disappeared from MR image by the 8th day. Of the serum chemistry tests, serum hepatic enzymes (ALT, AST) were significantly elevated for one week after cMSCs treatment. Histopathological findings also revealed infiltration of SPIO-containing cells into the parenchyma of kidney. On 35th day, histopathology, glomerular atrophy, tubular necrosis, and mineralization were found in the subcapsular cortex, with fibrosis of the interstitial tissues. In vivo MRI studies of stem cells were useful in determining the sequential location of stem cells in the renal parenchyma of healthy dogs. Allogenic stem cells administered via renal artery caused inflammation, tubular necrosis, mineralization, and fibrosis without functional complications.     

Plasma and Urine Neutrophil Gelatinase–Associated Lipocalin (NGAL) in Dogs with Acute Kidney Injury or Chronic Kidney Disease

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is a protein that is used in human medicine as a real‐time indicator of acute kidney injury (AKI).

Hypothesis

Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL‐to‐creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD).

Animals

18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI.

Methods

Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single‐injection plasma inulin clearance was performed in the healthy dogs.

Results

Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5–21.2), 22.0 ng/mL (7.7–62.3), and 48.3 ng/mL (5.7–469.0), respectively. UNCR was 2 × 10⁻⁸ (0–46), 1,424 × 10⁻⁸ (385–18,347), and 2,366 × 10⁻⁸ (36–994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027).

Conclusions and Clinical Importance

Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.