犬一侧输尿管全结扎引发不同时间肾积水及肾功能障碍的研究
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摘要
研究背景
肾脏占机体体重的0.5%,具有多种调节功能。其主要功能是通过调节细胞外液的含量并间接调节细胞内液。肾主要依靠滤过、重吸收和激素分泌发挥作用。此外,肾还能调节循环系统,包括血量,细胞外液量和全身动脉血压；调节细胞代谢物浓度、电解质及矿物质含量、体内离子平衡(如钾,钠,氯,磷,镁,钙)、酸碱平衡和血细胞比容和红细胞容积等。
肾是机体中最重要的器官之一。肾血量占心输出量的20～25%,每克肾组织提供4mL·min-1血流量,高于心脏、脑、活跃的骨骼肌等组织。肾是一个大的机能储备,但在临床上,常观测到一侧肾功能发病而另一侧无显著性影响。因此,在临床上,结合一些诊断仪器,通过评估肾解剖形态和功能完整性,可为肾功能诊断提供一个有效的方法。
肾功能不全常引起肾小球滤过率显着下降,从而导致氮质血症,即血浆中含过量含氮化合物,临床中常通过检测血浆或血液中肌酐、尿素氮,或结合两者浓度来判定是否出现氮质血症。根据病因的不同氮血症被划分为肾前性氮血症,肾性氮血症和肾后性氮血症。当泌尿道的完整性被破坏或尿液流出受阻时常发生肾后性氮血症发生。各种氮血症的共同特点是含氮废物电解质代谢紊乱的积累及体液性质的改变。根据患者症状并结合生化指标综合评价患者是否适合手术。
肾积水是由于部分或完全尿液流出受阻而引起的肾盂扩张并发肾组织压迫性萎缩,是一种相对少见的病例,如果仅一个肾发生积水,常难以被发现。造成肾积水的原因可能是输尿管、膀胱或尿道输尿管交界处的先天性畸形或狭窄。最常见的原因有因尿路结石、慢性炎症、肾盂,输尿管或膀胱(三角区)肿瘤引起的输尿管或尿道堵塞,不慎的缝合也会最终引起肾积水,常发生在卵巢子宫切除术,国外机构也常见与输尿管疾病手术中。
肾积水可能发生于单侧或双侧。单侧肾积水时,损伤发生前常发生广泛性肾盂或肾盏的囊性增大。伴随肾实质压力性萎缩和肾脏囊性肿大,动物常也能存活较长时间。最终引起肾严重肿大,形成无功能性囊腔,充满尿液或浆液性液体,并含有大量细菌。
研究意义
临床上可通过各种诊断方式诊断肾功能不全。除了血常规和血液生化分析,超声影像诊断也是常用的诊断方法。超声诊断具有非侵袭性,有利于提供解剖信息,包括肾脏的大小、形状和内部结构,并可诊断肾功损伤或腹腔积液。尿路造影是一个较好的诊断肾功能的方法。它不仅有助于观察未扩张的输尿管,也可有利于识别轻度扩张的肾盂或输尿管,以及确定创伤性尿漏的位置。
肾功能可间接地通过血浆或尿液中的某些物质排除(特别是P-肌酐和P-尿素)浓度进行定量评估。这些间接标志物可容易而迅速地测量,但在肾病的早期诊断其灵敏度较低；直到75%的肾功能已经丧失,其灵敏度才能升高。根据肾小球滤过、血流量或肾小管重吸收／分泌的消除动力学指标,以及清除的理念直接进行肾功能(如GFR和ERPF)的测试。虽然这些试验较费时且操作较繁琐,但是,它们的敏感性较高,故可允许早期肾功能降低的检测,尤其如肾小球滤过率(GFR),即每单位时间肾小球滤液所生成的超滤过量,被认为是最好的评估肾功能的方法。
研究结果
本试验选取24只6月龄至6岁健康成年杂种犬,体重介于6-11公斤。适应性饲养1周后,施行绝育或结扎手术,手术康复后随机分成4组,每组6只。实施左侧输尿管结扎术(建立输尿管阻塞模型)和颈静脉导管插入手术(用于采血),手术后第0天(即在输尿管结扎当天),第1,3,5,7,11,15和20天进行肾功能的定性和定量测试。如B型超声检查、静脉尿路造影、组织病理学检查、尿常规和尿蛋白测定等。
本试验测得的肾小球滤过率的正常值为2.769～7.705mL.min-1.kg-1,肾有效血流量的正常值为11.4-22.5mL.min-1.kg1。动物肾积水时,其肾小球滤过率显著下降,开始时正常值为2.582±0.399mL.mmin-1.kg-1,但到第3天时为1.483±0.303mL.min-1.kg-1,到第8天时为1.32±0.123mL.min-1.kg-1,第11天时为1.21±0.076mL.mmin-1.kg-1,第20天时为0.752±0.455mL.min-1.kg-1。肾贮量也有相似的下降,从开始时正常值100%下降到第3天时为57.4%；第8天时为51.1%；第11天时为46.86%；第20天时为29.12%。
输尿管结扎后3d,’肾有效血流量显著下降,从正常平均值的17.2土1.74mL.min-1.kg-1下降为10.23±1.06mL.min-1.kg-1。在结扎后的第5天、第8天、第11天,有效血流量有所波动,但都显著低于正常平均值,说明输尿管结扎后肾有效血流量下降。
通过血液、生化、尿常规和尿蛋白测定定量评定肾功能不全。血常规检测发现,试验犬的白细胞只在试验的第一天显著的增多(45.92±4.8×109.L-1；P<0.01),而随后的试验期间则无明显的变化。在输尿管结扎的第1天,立即出现中度的淋巴细胞增多和明显的粒细胞增多(28.92±2.85×109.L-；P<0.01),但在随后的试验期间粒细胞增多不明显。在试验期的第11天,血小板严重减少,差异显著；同时血象提示严重的再生性、红细胞正常(红细胞体积正常)、平均血红蛋白浓度正常的贫血。到第15天时,红细胞计数显著下降,降到4.47±±0.45x1012,血红蛋白降到93.8±±8.35g.L-1,血细胞比积降到29.3±2.74%,差异极显著(P<0.01).。
血清分析提示肾积水损伤是慢性的。生化分析结果提示试验动物有严重的低蛋白血症(28.72±3.85g.L-1,第11天,P<0.01)和低白蛋白血症(15.36±53.62g.L-1,第11天18.88±2.91g.L-1,第15天;P<0.01)。非常显著的尿酸指数(145.30±±69.20mmo1.L-1,第20天,P<0.01),,高氯血症酸中毒(126.65±±7.05mmo1.L-1,第20天.P<0.01)和重现的高钠血症(167.98±±1.35mmo1.L-1,第11天;169.55±±26.05mmo1.L-1,第20天；P<0.01)是最明显的表现,提示肾脏疾病进行性的恶化过程。
由于尿常规并没有发现在肾组织大部分被破坏之前尿液有明显变化,因此大部分尿比重紊乱可忽略不计,差异不显著,但在试验的第2、6、8、10、12天时除外(P<0.05),这些结果提示肾小管浓缩能力降低,由于肾积水引起的广泛的细胞损伤,尿蛋白没有显著变化,量也在正常的范围之内。由此可推测,由于完整的对侧肾的代偿作用,才使得尿比重变化基本可以忽略。
在评估试验动物肾功能不全的定性检查方法当中,B超检查在非侵入性检测手段中是最灵敏的,能直接观察到使肾组织解剖结构。左侧肾盂检查显示其极度膨大,从试验开始第0天大小为7.37±0.32mm变,第3天为11.78±±0.61mm(P<0.05).第12天为22±±1.43mm(P<0.01),第14天为24.1±1.66mm(P<0.01),第20天为26.1±3.4mmon Day20(P<0.01)。由于尿液蓄积造成的肾内压升高,左侧肾皮质厚度显著下降,第0天正常均值5.5土0.5mm,第10天的4±0.13mm10(P<0.05),第14天的3.27±±0.24mm(P<0.01)和第20天的3±0.31mm(P<0.01)。输尿管结扎后,左肾的长度一直不断增加,从第0天正常均值51.6±1.2mm变为第10天的64.45±±1.93和第14天时的68.45±2.63mm(P<0.01)。左肾的宽度和深度在结扎后也有相似的显著增加。左肾的宽度在试验开始时是28±±0.88mm,在第10天时为34.42±0.77mm,在第14天时为35.91±1.77mm(P<0.01)。左肾的深度也由正常时的均值25.87±0.65mm变为到第10天时的35.1±1.2mm和第20天时的40.28±2.8mm,差异极显著(P<0.01)。此外,随着肾损伤的加剧,特别是肾盂和输尿管内压力的增大,左侧输尿管的直径也显著变大；从试验开始零天的正常时均值1.0±1.0mm增加为第10天时的17.2±0.77mm和第20天时的23.28±2.44mm(P<0.01)。
X线造影也清晰地显示带有肾实质(皮质和髓质)细化和纤维化肾盂的膨大的输尿管。由于压迫萎缩,可以看到肾盂细束状延伸向肾皮质。组织病理学检查提示有细胞坏死和凋亡。长期的输尿管阻塞可以看到诱发了肾小管细胞凋亡的增加。此外,病理切片以严重的输尿管膨胀、肾小管萎缩、大量间质细胞和浸润单核细胞细胞间隙变大为特征。在各个切片上可见到出血,小管间质纤维化在本试验的后期也是明显的。
结论
本试验采用输尿管完全结扎诱导肾积水试验模型,对自然条件下因输尿管阻塞(如结石)而引起的肾积水进行评定。我们也尝试建立一种直接评价肾功能的检测方法,用血浆中菊粉清除率评定肾小球滤过率,用血浆中对氨基马尿酸清除率评定有效肾血量。各个方面的研究为今后进一步研究和建立直接测定肾功能的方法,及兽医临床肾功能衰减的早期检测起到了指导作用。
Background and Purpose of this Study
Obstructive uropathy due to calculi in the urinary tract is being diagnosed with an increasing frequency in dogs and cats. In case of unilateral ureteral involvement, the condition often passes by unnoticed, because of the presence of non-specific findings such as malaise or abdominal pain. If the condition is not diagnosed at an early stage, it can be devastating to the kidney and pave way for the state of post-renal azotemia, which leads to irreversible renal damage, and the degree of which depends directly on the duration and extent of the obstruction.
Modern clinical diagnostic modalities have revolutionized the diagnosis of urological disorders. B-mode Ultrasonography is amongst the first diagnostic tool which is relied upon, for directly visualizing and demonstrating the abnormalities of the internal architecture of soft tissues such as cysts, abscesses and hydronephrosis. Furthermore, because of the added benefits of least invasiveness and accurate localization of the lesions, ultrasonography augments collection of safer biopsy or fluid samples. Due to these benefits, it outshines the alternative diagnostic techniques of conventional and contrast radiography, which have limited uses. Besides these, histopathological findings, as determined through biopsy of the renal tissue, can further confirm early reduction in renal function by detecting changes at cellular level. In addition to these, direct quantitative measurement of renal function and hence pattern of progression of the disease can easily be ascertained by biochemistry, hematology, urinalysis and kinetic studies for plasma clearance of renal markers. These latter kinetic studies hold high specificity and sensitivity in direct quantification of the renal function, since these enable detection and extent of renal damage early in the course of renal disease.
The present study thus emphasizes the need for routine implementation of modern diagnostic aids for early detection and successful monitoring of progressive renal disease in pets.
Results of the Experimental Study
This experimental study was accomplished on24healthy mongrel dogs of either sex, aged between6months-6yrs and ranging in weight between6-11kg. The dogs were divided into4groups with6animals in each group; qualitative and quantitative tests of renal function were applied on each animal on Day0(i.e. before ureteral ligation), and
Days1,3,5,7,11,15and20post-ligation. Day0animals served as control. Before launching the experiments, appropriate preparations were made beforehand, for direct and indirect quantitative assessment of renal dysfunction (i.e. for kinetic studies of test markers, urinalysis and urine protein quantification). Preparations included sterilization of surgical instruments for use during the surgeries, preparation of chemical solutions required during the experimental study, surgeries performed on the experimental dogs, i.e. jugular catheter insertion (for convenient blood sampling), devocalization and subsequent laparotomies for ligation of the left ureter in each animal, for creating models of hydronephrosis.
The experimental data was statistically analysed by application of ANOVA. The normal range of GFR value measured in this experimental study was2.769-7.705mL. min-1. kg-1, while the normal range of ERPF values measured was11.4～22.5mL. min-1. kg1. In hydronephrotic animals, the significant decrease in GFR values was recorded from a normal value of2.582±0.399mL. min-1. kg-1on Day0, to1.483±0.303mL. min-1. kg-1on Day3(P<0.01);1.32±0.123mL. min-1. kg-1on Day8(P<0.01);1.21±0.076mL. min-1. kg-1on Day11(P<0.01), and0.752±0.455mL. min-1. kg-1on Day20(P<0.05). Renal reserve was also seen to decrease likewise, from a normal value of100%on Day0to57.4%on Day3;51.1%on Day8;46.86%on Day11, and29.12%on Day20.
The ERPF values were also seen to decrease significantly by Day3after ureteral ligation, from a mean normal value of17.2±1.74mL. min-1. kg-1to a mean value of10.23±1.06mL. min-1. kg-1(P<0.01). Later, on days5,8, and11post-ligation, the values were found to fluctuate, however, values remained significantly lower (i.e. P<0.05) than the normal mean value, and were indicative of a reduced ERPF than on Day0.
Quantitative assessment of renal dysfunction was also checked through hematology, biochemistry, and urinalysis and urine protein quantification.
Regarding hematology, the leukogram of the experimental dogs was suggestive of marked leukocytosis, with a highly significant value only on Day1(45.92±4.8x109. L-1; P<0.01), with no further profound changes in the later days. Moderate lymphocytosis (11.7±1.5x109. L-1. P<0.01) and marked granulocytosis (28.92±2.85x109. L-1; P<0.01) were also observed on Day1, immediately after the ureteral ligation and granulocytosis was insignificant during the rest of the experimental period. The thrombograms depicted severe and significant thrombocytopenia (53±9.6x109. L-1. P<0.05) on Day11of the experimental period; while the hemograms depicted a severe regenerative, normocytic (normal MCV), normochromic (normal MCHC) anemia. By Day15, RBC count was seen significantly to drop to4.47±0.45x1012.L-1, HGB to93.8±8.35g. L-1, and HCT to29.3±2.74%(P<0.01).
Besides this, various serum analytes depicted the chronic pattern of the hyronephrosis lesion. The biochemical profile was hence, clearly indicative of a highly significant hypoproteinemia (28.72±3.85g. L-1-Day11, P<0.01) and hypoalbuminemia (15.36±3.62g. L-1, Day11and18.88±2.91g. L-1, Day15; P<0.01) in the experimental animals. Highly significant uric acid indices (145.30±69.20mmol. L-1-Day20, P<0.01), hyperchloremic acidosis (126.65±7.05mmol. L-1-Day20, P<0.01) and recurrent hyperaatremia (167.98±1.35mmol. L-1-Day11, and169.55±26.05mmol. L-1-Day20; P<0.01) were the most conspicuous findings, suggestive of the progressive devastating pattern of the renal disease
Since urinalysis does not yield prominent changes in urine till most of the kidney tissue has become destroyed, thus mostly, the derangements in urine specific gravity were also negligible and insignificant, except on days2,6,8,10and12(P<0.05). These results indicated lowered tubular concentrating ability, due to extensive cellular damage produced as a result of hydronephrosis. Urine protein did not vary significantly; the quantity of urine proteins was usually found to be in the normal range. It was inferred that due to compensation by the intact contra-lateral kidney, changes in urine specific gravity largely remained subtle.
Amongst the qualitative tests performed for assessing renal dysfunction in experimental animals, B-mode ultrasonography was the most sensitive, least invasive one, enabling direct visual assessment of the condition of the kidney tissue. Measurements taken for left renal pelvis depicted an enormously dilation in size, from a mean normal value of7.37±0.32mm on Day0, significantly to11.78±0.61mm on Day3(P<0.05),22±1.43mm on Day12(P<0.01),24.1±1.66mm on Day14(P<0.01), and26.1±3.4mm on Day20(P<0.01), respectively. Likewise, due to the increased intra-renal pressure of accumulated urine, the left renal cortex also showed a significant decrease in thickness, from a mean normal value of5.5±0.5mm, to4±0.13mm on Day10(P<0.05),3.27±0.24mm on Day14(P<0.01), and3±0.31mm on Day20(P<0.01), respectively. Left renal length simultaneously increased significantly on all days post-ligation, from a mean normal value of51.6±1.2mm on Day0, to64.45±1.93on Day10, and68.45±2.63mm on Day14, respectively,(P<0.01). Left renal width and depth also depicted similar significant enlargements on all days post-ligation. Changes recorded in left renal width included a mean normal value of28±0.88mm on Day0, to34.42±0.77mm on Day10and35.91± 1.77mm on Day14, respectively,(P<0.01). Depth of the left kidney also showed significant increases from a mean normal value of25.87±0.65mm on Day0, to35.1±1.2mm on Day10, and40.28±2.8mm on Day20, respectively,(P<0.01). Besides this, the change in diameter of the left ureter depicted the most enormous significant enlargement, specifically due to the increased intra-pelvic and ureteral pressure, with progression of the renal lesion. Hence, from a mean normal value of1.0±1.0mm on Day0, the opening of the left ureter increased to17.2±0.77mm on Day10, and23.28±2.44mm on Day20, respectively,(P<0.01).
Contrast radiography (intravenous urography) was clearly indicative of a dilated ureter-filled pelvis with thinning and fibrosis of the renal parenchyma (cortex and medulla). Due to pressure atrophy, the pseudo-diverticulae of the renal pelvis was visualized as thin cords extending towards the cortex. Histopathology was suggestive of tissue necrosis and apoptosis. The long-standing ureteral obstruction was seen to induce an increase in the number of apoptotic renal tubular cells. Besides this, the sections were characterized with severe tubular dilatation, tubular atrophy, widened interstitial space with a greater number of interstitial cells and infiltrating mononuclear cells. Hemorrhage was also noticed in various sections, and tubulointerstitial fibrosis was evident in the later stages of the experimental study.
Conclusion
This present study, comprising of experimental models of hydronephrosis by complete ureteral ligation, was hence, conducted in order to assess the pattern of renal dysfunction, as may be produced in natural conditions by usual blockage of the ureter due to some reason, such as calculi. We have also tried to develop an easier method for direct renal function tests, by assessing plasma clearance of Inulin for GFR determination and plasma clearance of Para-aminohippurate for ERPF determination. This multi-directional study may, thus, prove a beacon-light for future research and development of more efficacious methods for direct determination of renal function, in veterinary clinical patients, for early detection of reduced renal function.
肾脏占机体体重的0.5%,具有多种调节功能。其主要功能是通过调节细胞外液的含量并间接调节细胞内液。肾主要依靠滤过、重吸收和激素分泌发挥作用。此外,肾还能调节循环系统,包括血量,细胞外液量和全身动脉血压；调节细胞代谢物浓度、电解质及矿物质含量、体内离子平衡(如钾,钠,氯,磷,镁,钙)、酸碱平衡和血细胞比容和红细胞容积等。
肾是机体中最重要的器官之一。肾血量占心输出量的20～25%,每克肾组织提供4mL·min-1血流量,高于心脏、脑、活跃的骨骼肌等组织。肾是一个大的机能储备,但在临床上,常观测到一侧肾功能发病而另一侧无显著性影响。因此,在临床上,结合一些诊断仪器,通过评估肾解剖形态和功能完整性,可为肾功能诊断提供一个有效的方法。
肾功能不全常引起肾小球滤过率显着下降,从而导致氮质血症,即血浆中含过量含氮化合物,临床中常通过检测血浆或血液中肌酐、尿素氮,或结合两者浓度来判定是否出现氮质血症。根据病因的不同氮血症被划分为肾前性氮血症,肾性氮血症和肾后性氮血症。当泌尿道的完整性被破坏或尿液流出受阻时常发生肾后性氮血症发生。各种氮血症的共同特点是含氮废物电解质代谢紊乱的积累及体液性质的改变。根据患者症状并结合生化指标综合评价患者是否适合手术。
肾积水是由于部分或完全尿液流出受阻而引起的肾盂扩张并发肾组织压迫性萎缩,是一种相对少见的病例,如果仅一个肾发生积水,常难以被发现。造成肾积水的原因可能是输尿管、膀胱或尿道输尿管交界处的先天性畸形或狭窄。最常见的原因有因尿路结石、慢性炎症、肾盂,输尿管或膀胱(三角区)肿瘤引起的输尿管或尿道堵塞,不慎的缝合也会最终引起肾积水,常发生在卵巢子宫切除术,国外机构也常见与输尿管疾病手术中。
肾积水可能发生于单侧或双侧。单侧肾积水时,损伤发生前常发生广泛性肾盂或肾盏的囊性增大。伴随肾实质压力性萎缩和肾脏囊性肿大,动物常也能存活较长时间。最终引起肾严重肿大,形成无功能性囊腔,充满尿液或浆液性液体,并含有大量细菌。
研究意义
临床上可通过各种诊断方式诊断肾功能不全。除了血常规和血液生化分析,超声影像诊断也是常用的诊断方法。超声诊断具有非侵袭性,有利于提供解剖信息,包括肾脏的大小、形状和内部结构,并可诊断肾功损伤或腹腔积液。尿路造影是一个较好的诊断肾功能的方法。它不仅有助于观察未扩张的输尿管,也可有利于识别轻度扩张的肾盂或输尿管,以及确定创伤性尿漏的位置。
肾功能可间接地通过血浆或尿液中的某些物质排除(特别是P-肌酐和P-尿素)浓度进行定量评估。这些间接标志物可容易而迅速地测量,但在肾病的早期诊断其灵敏度较低；直到75%的肾功能已经丧失,其灵敏度才能升高。根据肾小球滤过、血流量或肾小管重吸收／分泌的消除动力学指标,以及清除的理念直接进行肾功能(如GFR和ERPF)的测试。虽然这些试验较费时且操作较繁琐,但是,它们的敏感性较高,故可允许早期肾功能降低的检测,尤其如肾小球滤过率(GFR),即每单位时间肾小球滤液所生成的超滤过量,被认为是最好的评估肾功能的方法。
研究结果
本试验选取24只6月龄至6岁健康成年杂种犬,体重介于6-11公斤。适应性饲养1周后,施行绝育或结扎手术,手术康复后随机分成4组,每组6只。实施左侧输尿管结扎术(建立输尿管阻塞模型)和颈静脉导管插入手术(用于采血),手术后第0天(即在输尿管结扎当天),第1,3,5,7,11,15和20天进行肾功能的定性和定量测试。如B型超声检查、静脉尿路造影、组织病理学检查、尿常规和尿蛋白测定等。
本试验测得的肾小球滤过率的正常值为2.769～7.705mL.min-1.kg-1,肾有效血流量的正常值为11.4-22.5mL.min-1.kg1。动物肾积水时,其肾小球滤过率显著下降,开始时正常值为2.582±0.399mL.mmin-1.kg-1,但到第3天时为1.483±0.303mL.min-1.kg-1,到第8天时为1.32±0.123mL.min-1.kg-1,第11天时为1.21±0.076mL.mmin-1.kg-1,第20天时为0.752±0.455mL.min-1.kg-1。肾贮量也有相似的下降,从开始时正常值100%下降到第3天时为57.4%；第8天时为51.1%；第11天时为46.86%；第20天时为29.12%。
输尿管结扎后3d,’肾有效血流量显著下降,从正常平均值的17.2土1.74mL.min-1.kg-1下降为10.23±1.06mL.min-1.kg-1。在结扎后的第5天、第8天、第11天,有效血流量有所波动,但都显著低于正常平均值,说明输尿管结扎后肾有效血流量下降。
通过血液、生化、尿常规和尿蛋白测定定量评定肾功能不全。血常规检测发现,试验犬的白细胞只在试验的第一天显著的增多(45.92±4.8×109.L-1；P<0.01),而随后的试验期间则无明显的变化。在输尿管结扎的第1天,立即出现中度的淋巴细胞增多和明显的粒细胞增多(28.92±2.85×109.L-；P<0.01),但在随后的试验期间粒细胞增多不明显。在试验期的第11天,血小板严重减少,差异显著；同时血象提示严重的再生性、红细胞正常(红细胞体积正常)、平均血红蛋白浓度正常的贫血。到第15天时,红细胞计数显著下降,降到4.47±±0.45x1012,血红蛋白降到93.8±±8.35g.L-1,血细胞比积降到29.3±2.74%,差异极显著(P<0.01).。
血清分析提示肾积水损伤是慢性的。生化分析结果提示试验动物有严重的低蛋白血症(28.72±3.85g.L-1,第11天,P<0.01)和低白蛋白血症(15.36±53.62g.L-1,第11天18.88±2.91g.L-1,第15天;P<0.01)。非常显著的尿酸指数(145.30±±69.20mmo1.L-1,第20天,P<0.01),,高氯血症酸中毒(126.65±±7.05mmo1.L-1,第20天.P<0.01)和重现的高钠血症(167.98±±1.35mmo1.L-1,第11天;169.55±±26.05mmo1.L-1,第20天；P<0.01)是最明显的表现,提示肾脏疾病进行性的恶化过程。
由于尿常规并没有发现在肾组织大部分被破坏之前尿液有明显变化,因此大部分尿比重紊乱可忽略不计,差异不显著,但在试验的第2、6、8、10、12天时除外(P<0.05),这些结果提示肾小管浓缩能力降低,由于肾积水引起的广泛的细胞损伤,尿蛋白没有显著变化,量也在正常的范围之内。由此可推测,由于完整的对侧肾的代偿作用,才使得尿比重变化基本可以忽略。
在评估试验动物肾功能不全的定性检查方法当中,B超检查在非侵入性检测手段中是最灵敏的,能直接观察到使肾组织解剖结构。左侧肾盂检查显示其极度膨大,从试验开始第0天大小为7.37±0.32mm变,第3天为11.78±±0.61mm(P<0.05).第12天为22±±1.43mm(P<0.01),第14天为24.1±1.66mm(P<0.01),第20天为26.1±3.4mmon Day20(P<0.01)。由于尿液蓄积造成的肾内压升高,左侧肾皮质厚度显著下降,第0天正常均值5.5土0.5mm,第10天的4±0.13mm10(P<0.05),第14天的3.27±±0.24mm(P<0.01)和第20天的3±0.31mm(P<0.01)。输尿管结扎后,左肾的长度一直不断增加,从第0天正常均值51.6±1.2mm变为第10天的64.45±±1.93和第14天时的68.45±2.63mm(P<0.01)。左肾的宽度和深度在结扎后也有相似的显著增加。左肾的宽度在试验开始时是28±±0.88mm,在第10天时为34.42±0.77mm,在第14天时为35.91±1.77mm(P<0.01)。左肾的深度也由正常时的均值25.87±0.65mm变为到第10天时的35.1±1.2mm和第20天时的40.28±2.8mm,差异极显著(P<0.01)。此外,随着肾损伤的加剧,特别是肾盂和输尿管内压力的增大,左侧输尿管的直径也显著变大；从试验开始零天的正常时均值1.0±1.0mm增加为第10天时的17.2±0.77mm和第20天时的23.28±2.44mm(P<0.01)。
X线造影也清晰地显示带有肾实质(皮质和髓质)细化和纤维化肾盂的膨大的输尿管。由于压迫萎缩,可以看到肾盂细束状延伸向肾皮质。组织病理学检查提示有细胞坏死和凋亡。长期的输尿管阻塞可以看到诱发了肾小管细胞凋亡的增加。此外,病理切片以严重的输尿管膨胀、肾小管萎缩、大量间质细胞和浸润单核细胞细胞间隙变大为特征。在各个切片上可见到出血,小管间质纤维化在本试验的后期也是明显的。
结论
本试验采用输尿管完全结扎诱导肾积水试验模型,对自然条件下因输尿管阻塞(如结石)而引起的肾积水进行评定。我们也尝试建立一种直接评价肾功能的检测方法,用血浆中菊粉清除率评定肾小球滤过率,用血浆中对氨基马尿酸清除率评定有效肾血量。各个方面的研究为今后进一步研究和建立直接测定肾功能的方法,及兽医临床肾功能衰减的早期检测起到了指导作用。
Background and Purpose of this Study
Obstructive uropathy due to calculi in the urinary tract is being diagnosed with an increasing frequency in dogs and cats. In case of unilateral ureteral involvement, the condition often passes by unnoticed, because of the presence of non-specific findings such as malaise or abdominal pain. If the condition is not diagnosed at an early stage, it can be devastating to the kidney and pave way for the state of post-renal azotemia, which leads to irreversible renal damage, and the degree of which depends directly on the duration and extent of the obstruction.
Modern clinical diagnostic modalities have revolutionized the diagnosis of urological disorders. B-mode Ultrasonography is amongst the first diagnostic tool which is relied upon, for directly visualizing and demonstrating the abnormalities of the internal architecture of soft tissues such as cysts, abscesses and hydronephrosis. Furthermore, because of the added benefits of least invasiveness and accurate localization of the lesions, ultrasonography augments collection of safer biopsy or fluid samples. Due to these benefits, it outshines the alternative diagnostic techniques of conventional and contrast radiography, which have limited uses. Besides these, histopathological findings, as determined through biopsy of the renal tissue, can further confirm early reduction in renal function by detecting changes at cellular level. In addition to these, direct quantitative measurement of renal function and hence pattern of progression of the disease can easily be ascertained by biochemistry, hematology, urinalysis and kinetic studies for plasma clearance of renal markers. These latter kinetic studies hold high specificity and sensitivity in direct quantification of the renal function, since these enable detection and extent of renal damage early in the course of renal disease.
The present study thus emphasizes the need for routine implementation of modern diagnostic aids for early detection and successful monitoring of progressive renal disease in pets.
Results of the Experimental Study
This experimental study was accomplished on24healthy mongrel dogs of either sex, aged between6months-6yrs and ranging in weight between6-11kg. The dogs were divided into4groups with6animals in each group; qualitative and quantitative tests of renal function were applied on each animal on Day0(i.e. before ureteral ligation), and
Days1,3,5,7,11,15and20post-ligation. Day0animals served as control. Before launching the experiments, appropriate preparations were made beforehand, for direct and indirect quantitative assessment of renal dysfunction (i.e. for kinetic studies of test markers, urinalysis and urine protein quantification). Preparations included sterilization of surgical instruments for use during the surgeries, preparation of chemical solutions required during the experimental study, surgeries performed on the experimental dogs, i.e. jugular catheter insertion (for convenient blood sampling), devocalization and subsequent laparotomies for ligation of the left ureter in each animal, for creating models of hydronephrosis.
The experimental data was statistically analysed by application of ANOVA. The normal range of GFR value measured in this experimental study was2.769-7.705mL. min-1. kg-1, while the normal range of ERPF values measured was11.4～22.5mL. min-1. kg1. In hydronephrotic animals, the significant decrease in GFR values was recorded from a normal value of2.582±0.399mL. min-1. kg-1on Day0, to1.483±0.303mL. min-1. kg-1on Day3(P<0.01);1.32±0.123mL. min-1. kg-1on Day8(P<0.01);1.21±0.076mL. min-1. kg-1on Day11(P<0.01), and0.752±0.455mL. min-1. kg-1on Day20(P<0.05). Renal reserve was also seen to decrease likewise, from a normal value of100%on Day0to57.4%on Day3;51.1%on Day8;46.86%on Day11, and29.12%on Day20.
The ERPF values were also seen to decrease significantly by Day3after ureteral ligation, from a mean normal value of17.2±1.74mL. min-1. kg-1to a mean value of10.23±1.06mL. min-1. kg-1(P<0.01). Later, on days5,8, and11post-ligation, the values were found to fluctuate, however, values remained significantly lower (i.e. P<0.05) than the normal mean value, and were indicative of a reduced ERPF than on Day0.
Quantitative assessment of renal dysfunction was also checked through hematology, biochemistry, and urinalysis and urine protein quantification.
Regarding hematology, the leukogram of the experimental dogs was suggestive of marked leukocytosis, with a highly significant value only on Day1(45.92±4.8x109. L-1; P<0.01), with no further profound changes in the later days. Moderate lymphocytosis (11.7±1.5x109. L-1. P<0.01) and marked granulocytosis (28.92±2.85x109. L-1; P<0.01) were also observed on Day1, immediately after the ureteral ligation and granulocytosis was insignificant during the rest of the experimental period. The thrombograms depicted severe and significant thrombocytopenia (53±9.6x109. L-1. P<0.05) on Day11of the experimental period; while the hemograms depicted a severe regenerative, normocytic (normal MCV), normochromic (normal MCHC) anemia. By Day15, RBC count was seen significantly to drop to4.47±0.45x1012.L-1, HGB to93.8±8.35g. L-1, and HCT to29.3±2.74%(P<0.01).
Besides this, various serum analytes depicted the chronic pattern of the hyronephrosis lesion. The biochemical profile was hence, clearly indicative of a highly significant hypoproteinemia (28.72±3.85g. L-1-Day11, P<0.01) and hypoalbuminemia (15.36±3.62g. L-1, Day11and18.88±2.91g. L-1, Day15; P<0.01) in the experimental animals. Highly significant uric acid indices (145.30±69.20mmol. L-1-Day20, P<0.01), hyperchloremic acidosis (126.65±7.05mmol. L-1-Day20, P<0.01) and recurrent hyperaatremia (167.98±1.35mmol. L-1-Day11, and169.55±26.05mmol. L-1-Day20; P<0.01) were the most conspicuous findings, suggestive of the progressive devastating pattern of the renal disease
Since urinalysis does not yield prominent changes in urine till most of the kidney tissue has become destroyed, thus mostly, the derangements in urine specific gravity were also negligible and insignificant, except on days2,6,8,10and12(P<0.05). These results indicated lowered tubular concentrating ability, due to extensive cellular damage produced as a result of hydronephrosis. Urine protein did not vary significantly; the quantity of urine proteins was usually found to be in the normal range. It was inferred that due to compensation by the intact contra-lateral kidney, changes in urine specific gravity largely remained subtle.
Amongst the qualitative tests performed for assessing renal dysfunction in experimental animals, B-mode ultrasonography was the most sensitive, least invasive one, enabling direct visual assessment of the condition of the kidney tissue. Measurements taken for left renal pelvis depicted an enormously dilation in size, from a mean normal value of7.37±0.32mm on Day0, significantly to11.78±0.61mm on Day3(P<0.05),22±1.43mm on Day12(P<0.01),24.1±1.66mm on Day14(P<0.01), and26.1±3.4mm on Day20(P<0.01), respectively. Likewise, due to the increased intra-renal pressure of accumulated urine, the left renal cortex also showed a significant decrease in thickness, from a mean normal value of5.5±0.5mm, to4±0.13mm on Day10(P<0.05),3.27±0.24mm on Day14(P<0.01), and3±0.31mm on Day20(P<0.01), respectively. Left renal length simultaneously increased significantly on all days post-ligation, from a mean normal value of51.6±1.2mm on Day0, to64.45±1.93on Day10, and68.45±2.63mm on Day14, respectively,(P<0.01). Left renal width and depth also depicted similar significant enlargements on all days post-ligation. Changes recorded in left renal width included a mean normal value of28±0.88mm on Day0, to34.42±0.77mm on Day10and35.91± 1.77mm on Day14, respectively,(P<0.01). Depth of the left kidney also showed significant increases from a mean normal value of25.87±0.65mm on Day0, to35.1±1.2mm on Day10, and40.28±2.8mm on Day20, respectively,(P<0.01). Besides this, the change in diameter of the left ureter depicted the most enormous significant enlargement, specifically due to the increased intra-pelvic and ureteral pressure, with progression of the renal lesion. Hence, from a mean normal value of1.0±1.0mm on Day0, the opening of the left ureter increased to17.2±0.77mm on Day10, and23.28±2.44mm on Day20, respectively,(P<0.01).
Contrast radiography (intravenous urography) was clearly indicative of a dilated ureter-filled pelvis with thinning and fibrosis of the renal parenchyma (cortex and medulla). Due to pressure atrophy, the pseudo-diverticulae of the renal pelvis was visualized as thin cords extending towards the cortex. Histopathology was suggestive of tissue necrosis and apoptosis. The long-standing ureteral obstruction was seen to induce an increase in the number of apoptotic renal tubular cells. Besides this, the sections were characterized with severe tubular dilatation, tubular atrophy, widened interstitial space with a greater number of interstitial cells and infiltrating mononuclear cells. Hemorrhage was also noticed in various sections, and tubulointerstitial fibrosis was evident in the later stages of the experimental study.
Conclusion
This present study, comprising of experimental models of hydronephrosis by complete ureteral ligation, was hence, conducted in order to assess the pattern of renal dysfunction, as may be produced in natural conditions by usual blockage of the ureter due to some reason, such as calculi. We have also tried to develop an easier method for direct renal function tests, by assessing plasma clearance of Inulin for GFR determination and plasma clearance of Para-aminohippurate for ERPF determination. This multi-directional study may, thus, prove a beacon-light for future research and development of more efficacious methods for direct determination of renal function, in veterinary clinical patients, for early detection of reduced renal function.
引文
[1]Kunkel PA. The number and size of the glomeruli in the kidney of several species [J]. Bull John Hopkins Hosp,1930,47:285-291
[2]Rytand DA. The number and size of mammalian glomeruli as related to kidney and body weight, with methods for their enumeration and measurement [J]. Am J Anat,1938,62 (4):507-520
[3]Vimtrup BJ. On the number, shape, structure, and surface area of the glomeruli in the kidneys of man and mammals [J]. Am J Anat,1928,41:123-151
[4]Brown SA, Barsanti JA, Finco DR. Determinants of glomerular ultrafiltration in cats [J]. Am J Vet Res. 1993,54:970-975
[5]Finco DR, Duncan JR. Relationship of glomerular number and diameter to body size of the dog [J]. Am J Vet Res,1972,33:2447-2450
[6]Gimonet V, Bussieres L, Medjebeur AA, et al. Nephrogenesis and angiotensin 11 receptor subtypes gene expression in the fetal lamb [J]. Am J Physiol,1998,274:F 1062-69
[7]Horster M, Kemler BJ, Valtin H. Intracortical distribution of number and volume of glomeruli during postnatal maturation in the dog [J]. J Clin Invest,1971.50:796-800
[8]Bankir L, de Rouffignac C. Urinary concentrating ability:insights from comparative anatomy [J]. Am J Physiol 1985,249:R 643-666
[9]Kriz W, Bankir L. A standard nomenclature for structures of the kidney. The renal Commission of the International Union of Physiological Sciences (IUPS) [J]. Kidney Int,1988,33:1-7
[10]Pallone TL, Silldorff EP, Turner MR. Intrarenal blood flow:microvascular anatomy and the regulation of medullary perfusion [J]. Clin Exp Pharmacol Physiol,1998,25:383-392
[11]Brown SA, Finco DR, Navar LG. Impaired renal autoregulatory ability in dogs with reduced renal mass [J]. J Am SocNephrol,1995,5:1768-1774
[12]Navar LG, Bell PD, White RW, et al. Evaluation of the single glomerular filtration coefficient in the dog [J]. Kidney Int,1977,12:137-149
[13]Tryggvason K. Unravelling the mechanism of glomerular filtration [J]. J Am Soc Nephroi,1999,10: 2440-2445
[14]Reilly RF, Ellison DH. Mammalian distal tubule:physiology, pathophysiology, and molecular anatomy [J]. Physiol Rev,2000,80:277-313
[15]Fisher JW. Erythropoietin:physiology and pharmacology update [J]. Exp Biol Med (Maywood),2003. 228:1-14
[16]Ebert R, Schutze N, Adamski J, et al. Vitamin D signaling is modulated on multiple levels in health and disease [J]. Mol Cell Endocrin,2006,248:149-159
[17]DiBartola SP. Renal Disease:Clinical approach and laboratory evaluation. SJ Ettinger and EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., Saunders, Elsevier Inc, Philadelphia, USA, 2005, p.1716-1730
[18]Cowgill LD, Francey T. Acute Uremia. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., Saunders, Elsevier Inc, Philadelphia, USA,2005, p.1731-1734
[19]Senior DF. Urinary Disorders. Michael S (Ed.), Clinical medicine of the Dog and Cat [M],2nd Ed.. Manson Publishing Ltd. (The Veterinary Press),2003, p.409-453
[20]Kahn CM, Line S, Aiello SE. Urinary System. CM Kahn, S Line, SE Aiello (Eds.), The Merck Veterinary Manual [M],9th Ed., Merck and Co. Inc., Whitehouse Station, NJ, USA,2005, p.1249-1287
[21]Vegad JL, Katiyar AK. Urinary System. Textbook of Veterinary Systemic Pathology [M], 1st Ed., International Book Distributing Company, Lucknow, India,1998, p.226-227
[22]Brown SA. Pathophysiology and Therapeutics of Urinary Tract Diseases. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA.2003, p.1583-1594
[23]Braun JP, Lefebvre HP. Kidney Function and Damage. JJ Kaneko, JW Harvey, LB Michael (Eds.), Clinical Biochemistry of Domestic Animals [M],6th Ed., Academic Press, Elsevier Inc., California, USA, 2008, p.490-510
[24]Park R, Rabinowitz L. Effect of reduced glomerular filtration rate on the fractional excretion of urea in the dog [J]. Proc Soc Exp Biol Med,1969,132:27-29
[25]Nyland TQ Mattoon JS, Herrgesell EJ, et al. Urinary Tract. R Kersey, D LeMelledo (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., Saunders, Elsevier Inc., Philadelphia, USA,2002, p.158-195
[26]Rawlings AC, Bjorling DE, Christie BA. Principles of Urinary Tract Surgery. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.1594-1606
[27]Wood AKW, McCarthy PH. Ultrasonographic-anatomic correlation and an imaging protocol of the normal canine kidney [J]. Am J Vet Res 1990,51:103-108
[28]Yeager AE, Anderson Wl. Study of association between histologic features and echogenicity of architecturally normal cat kidneys [J]. Am J Vet Res,1989,50:860-863
[29]Biller DS, Kantrowitz B, Partington BP, et al. Diagnostic ultrasound of the urinary bladder [J]. J Am Anim HospAssoc,1990,26:397-402
[30]Pugh CR, Arger PH, Sehgal CM. Power, spectral, and color flow Doppler enhancement by a new ultrasonographic contrast agent [J]. J Ultrasound Med,1996,15(12):843-852
[31]Barr FJ. Evaluation of ultrasound as a method of assessing renal size in the dog [J]. J Small Anim Pract 1990,31:174-179
[32]Walter PA, Feeney DA, Johnston GR, et al. Feline renal ultrasonography:quantitative analyses of imaged anatomy [J]. Am J Vet Res,1987,48 (4):596-599
[33]Hager DA, Nyland TG, Fisher P. Ultrasound-guided biopsy of the canine liver, kidney, and prostate [J] Vet Radiol,1985,26 (3):82-88
[34]Konde LJ, Wrigley RH, Park RD, et al. Ultrasonographic anatomy of the normal canine kidney [J]. Vet Radiol,1984,25:173-178
[35]Walter PA, Feeney DA, Johnston GR, et al. Ultrasonographic evaluation of renal parenchymal diseases in dogs:32 cases (1981-1986) [J].J Am Vet Med Assoc,1987,191:999-1007
[36]Nyland TG, Fisher PE, Gregory CR, et al. Ultrasonographic evaluation of renal size in dogs with acute allograft rejection [J]. Vet Radiol Ultrasound,1997,38:55-61
[37]Pollard R, Nyland TG, Bernsteen L, et al. Ultrasonographic evaluation of renal autografts in normal cats [J]. Vet Radiol Ultrasound,1999,40 (4):380-385
[38]Peshin PK. Contrast materials and techniques. AP Singh (Ed.), Veterinary Radiology [M],1st Ed., CBS Publishers and Distributors, Delhi, India,1994, p.178-215
[39]Johnston GR, Walter PA, Feeney DA. Diagnostic imaging of the urinary tract CA Osborne, DR Finco (Eds.), Canine and Feline Nephrology and Urology [M], Ist Ed., Williams & Wilkins, Baltimore, USA, 1995, p.230-276
[40]Lord PF, Scott RC, Chan KF, et al. Intravenous urography for evaluation of renal diseases in small animals [J]. J Am Anim Hosp Assoc,1974,10:139
[41]Pechman RD. Urinary trauma in dogs and cats:a review [J]. J Am Anim Hosp Assoc,1982,18:33
[42]Feeney DA, Thrall DE, Barber DL, et al. Normal canine urogram:effects of dose, time, and individual dog variation [J]. Am J Vet Res,1979,40 (11):1596-604
[43]Feeney DA, et al. The excretory urogram. Parts Ⅰ and Ⅱ [J]. Compend Contin Educ Pract Vet,1982,4:233
[44]Thornhill JA, Cechner PE. Traumatic injuries to the kidneys, ureter, bladder and urethra [J]. Vet Clin North Am,1981,11:157
[45]Ihle SL, Kostolich M. Acute renal failure associated with contrast medium administration in a dog [J]. J Am Vet Med,1991,199:899-901
[46]Rivers BJ, Walter PA, Polzin DJ. Ultrasonographic-guided, percutaneous antegrade pyelography: technique and clinical application in the dog and cat [J]. J Am Anim Hosp Assoc,1997,33:61-68
[47]Bricker NS, Morrin PA, Kime SW, Jr. The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis" [J]. J Am Soc Nephrol,1997,8:1470-1476
[48]Swaminathan R, Major P, Sneider H, et al. Serum creatinine and fat-free mass (lean body mass) [J]. CJin Chem,2000,46:1695-1696
[49]Price GS, Frazier DL. Use of body surface area (BSA)-based dosages to calculate chemotherapeutic drug dos in dogs:1. potential problems with current BSA formulae [J]. J Vet Intern Med,1998,12:267-271
[50]Peters AM, Henderson BL, Lui D. Indexed glomerular filtration rate as a function of age and body size [J]. Clin Sci,2000,98:439-444
[51]Gleadhill A. Evaluation of screening tests for renal insufficiency in the dog [J]. J Small anim Pract,1994, 35:391-396
[52]Gleadhill A, Michell AR. Evaluation of iohexol as a marker for the clinical measurement of glomerular filtration rate in dogs [J]. Res Vet Sci,1996,60:117-121
[53]Grubb A, Nordin G. Notable steps in obtaining improved estimates for glomerular filtration rate [J}. CJin Chem,2006,52:169-170
[54]Finco DR, Brown SA, Vaden SL, et al. Relationship between plasma creatinine concentration and glomerular filtration rate in dogs [J]. J Vet Pharmacol Ther,1995,18:418-421
[55]Heiene R, Moe L. Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog:a review [J]. J Vet Intern Med,1998,12:401-414
[56]Shannon JA. The excretion of inulin in the dog [J]. Am J Physiol,1935,112:405-413
[57]Watson AD, Lefebvre HP, Concordet D, et al. Plasma exogenous creatinine clearance test in dogs: comparison with other methods and proposed limited sampling strategy [J]. J Vet Intern Med,2002a,16: 22-23
[58]Osborne CA. Techniques of urine collection and preservation. CA Osborne, DR Finco (Eds.), Canine and Feline Nephrology and Urology [M], Williams and Wilkins, Baltimore, USA,1995, p.100-121
[59]Ladd M, Liddle L, Gagnon JA. Renal excretion of inulin, creatinine, and ferrocyanide, at normal and reduced clearance levels in the dog [J]. Am J Physiol,1956,184:505-514
[60]Bing J, Effersoe P. Comparative tests of the thiosulphate and creatinine clearance in rabbits and cats [J]. Acta Physiol Scand,1948,15:231-236
[61]Dalton RG. Renal function in neonatal calves:inulin, thiosulphate, and para-aminohippuric acid clearance [J]. BrVet J,1968,124:498-502
[62]Maddison JE, Pascoe PJ, Jansen BS. Clinical evaluation of sodium sulfanilate clearance for the diagnosis of renal disease in dogs [J]. J Am Vet Med Assoc,1984,185:961-965
[63]Ross LA, Finco DR. Relationship of selected clinical renal function tests to glomerular filtration rate and renal blood flow in cats [J]. Am J Vet Res,1981,42:1704-1710
[64]Bovee KC, Joyce T. Clinical evaluation of glomerular function:24-hour creatinine clearance in dogs [J]. J Am Vet Med Assoc,1979,174:488-491
[65]Finco DR, Coulter DB, Barsanti JA. Simple, accurate method for clinical estimation of glomerular filtration rate in the dog [J]. Am J Vet Res,1981,42:1874-1877
[66]Finco DR, Brown SA, Crowell WA, et al. Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass [J]. Am J Vet Res 1991,52:1029-1032
[67]Moe L, Heiene R. Estimation of glomerular filtration rate in dogs with 99M-Tc-DTPA and iohexol [J]. Res Vet Sci,1995,58:138-143
[68]Brown SA, Finco DR, Boudinot FD, et al. Evaluation of a single-injection method, using iohexol, for estimating glomerular filtration rate in cats and dogs [J]. Am J Vet Res 1996,57:105-110
[69]Drost WT, Henry GA, Meinkoth JH, et al. The effects of a unilateral ultrasound-guided renal biopsy on renal function in healthy sedated cats [J]. Vet Radiol Ultrasound,2000,41:57-62
[70]Uribe D, Krawiec DR, Twardock AR. Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc-diethylenetriaminepentaacetic acid [J]. Am J Vet Res 1992,53:1101-1107
[71]Daniel GB, Mitchell SK, Mawby D. Renal nuclear medicine:a review [J] Vet Radiol Ultrasound.1999, 40:572-587
[72]Biwenga WJ, van den Brom WE. Assessment of glornerular filtration rate in dogs with renal insufficiency: analysis of the 51Cr-EDTA clearanace and its relation to the plasma concentrations of urea and creatinine [J]. Res Vet Sci,1981,30:158-160
[73]Matthews HK, Andrews FM, Daniel GB, et al. Comparison of standard and radionuclide methods for measurement of glomerular filtration rate and effective renal blood flow in female horses [J]. Am J Vet Res,1992,53:1612-1616
[74]Walsh DM, Royal HD. Evaluation of a single injection of 99m-Tc-Iabeled diethylenetraminepentaacetic acid for measuring glomerular filtration rate in horses [J]. Am J Vet Res,1992,53:776-780
[75]Pihl B, Nosslin B. The single injection technique for determination of renal clearance. I. clearance of iothalamate and iodohippurate in dogs [J]. Scan J Urol Nephrol,1974,8:138-146
[76]Summerville DA, Treves ST. Single plasma sample technique of glomerular filtration rate measurement [J]. J Nucl Med Allied Sci,1986,30:177-184
[77]Brown SA, Haberman C, Finco DR. Use of plasma clearance of inulin for estimating glomerular filtration rate in cats [J]. Am J Vet Res,1996,57:1702-1705
[78]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci,1998,64:151-156
[79]Barthez PY, Hornof WJ, Cowgill LD, et al. Comparison between the scintigraphic uptake and plasma clearance of 99mTc-diethylenetriamine penta-acetic acid (DTPA) for the evaluation of the glomerular filtration rate in dogs [J]. Vet Radiol Ultrasound,1998,39:470-474
[80]Kampa N, Wennstrom U, Lord P, et al. Effect of region of interest selection and uptake measurement on glomerular filtration rate measured by 99mTc-DTPA scintigraphy in dogs [J]. Vet Radiol Ultrasound, 2002,43 (4):383-391
[81]Krawiec DR, Badertscher RR 2nd, Twardock AR, et al. Evaluation of 99mTc-diethylenetriamine penta-acetic acid nuclear imaging for quantitative determination of glomerular filtration rate of dogs [J]. Am J Vet Res 1986,47 (10):2175-2179
[82]Rogers KS, Komkov A, Brown SA, et al. Comparison of four methods of estimating the glomerular filtration rate in cats [J]. Am J Vet Res,1991,52 (6):961-964
[83]Finco DR. Measurement of glomerular filtration rate via urinary clearance of inulin and plasma clearance of Tc99th penetate and exogenous creattnine in dogs [J]. Am J Vet Res,2005,66:1046-1055
[84]Gagnon JA, Schrier RW, Weis TP, et al. Clearance of iothalamate-125 I as a measure of glomerular filtration rate in the dog [J]. J Appl Physiol,1971,30:774-778
[85]Izzat NN, Rosborough JP. Renal function in conscious dogs:potential effect of gender on measurement [J]. Res Exp Med,1989,189:371-379
[86]Miyamoto K. Use of plasma clearance of iohexol for estimating glomerular filtration rate in cats [J]. Am J Vet Res,2001b,62:572-575
[87]Fettman MJ, Allen TA, Wilke WL, et al. Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats [J]. Am J Vet Res,1985,46:482-485
[88]Thrall MA. Laboratory evaluation of renal function. DB Troy (Ed.), Veterinary Hematology and Clinical Chemistry [M], Lippincott Williams and Wilkins, Baltimore, USA,2004, p:7:91
[89]Marks PW, Rosovsky R. Hematologic manifestations of systemic disease:Liver and Renal Disease. R Hoffman, EJ Benz Jr., SJ Shattil, B Furie, LE Silberstein, P McGlave, H Heslop (Eds.), Hematology: Basic Principles and Practice [M],5th Ed., Churchill Livingstone, An imprint of Elsevier Inc., USA,2008, p.2303-2308
[90]Hocking WG. Hematologic abnormalities in patients with renal diseases [J]. Hematol Oncol Clin North Am 1987,1(2):229-260
[91]Schiller GJ, Berkman SA. Hematologic aspects of renal insufficiency [J]. Blood Rev,1989,3(3):141-6
[92]Thrall MA. Non-regenerative anemia. DB Troy (Ed.), Veterinary Hematology and Clinical Chemistry [M], Lippincott Williams and Wilkins, Baltimore, USA,2004, p.89-93
[93]Fried W. Hematologic complications of chronic renal failure [J]. Med Clin North Am,1978,62(6): 1363-79
[94]Naets JP. Hematologic disorders in renal failure [J]. Nephron,1975,14(2):181-94
[95]Radin MJ. Interpretation of Biochemical Profiles. W R Fenner (Ed.), Quick reference to Veterinary Medicine [M],3rd Ed. Wiley-Blackwell Publishing Co.,2000, p.166-176
[96]Wen JG, Frokiaer J, Jorgensen TM, et al. Obstructive nephropathy:an update of the experimental research [J]. Urol Res,1999,27:29-39
[97]Zhou Y, Takahashi G, Shinagawa T, et al. Increased transforming growth factor-β1 and tubulointerstitial fibrosis in rats with congenital hydronephrosis [J]. Int J Urol 2002,9:491-500
[98]Tanji N. Yokoyama M, Terada N, et al. Renal tubular apoptosis after release of ureteral obstruction in the rat kidney [J]. Int J Urol,1998,5:256-261
[1]Barbour GL, Crumb CK, Boyd CM. et al. Comparison of inulin, iothalamate, and 99mTc-DTPA for measurement of glomerular filtration rate [J]. J Nuc Med,1976,17 (4):317-320
[2]Kim EK, Onesti G, Ramirez O. et al. Creatinine clearance in renal disease. A reappraisal [J]. Brit Med J, 1969,4:11-14
[3]Luippold G, Schneider S, Stefanescu A, et al. Dopamine D2-like receptors and amino acid-induced glomerular hyperfiltration in humans [J]. Brit J Clin Pharm,2001.51 (5):415-421
[4]Finco DR, Brown SA, Crowelf WA, et al. Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass [J]. Am J Vet Res,1991,52:1029-1032
[5]Moe L, Heiene R. Estimation of glomerular filtration rate in dogs with 99mTc-DTPA and iohexol [J]. Res Vet Sci,1995,58:138-143
[6]Gleadhill A, Peters AM, Michell AR. A simple method for measuring glomerular filtration rate in dogs [J]. Res VetSci,1995,59:118-123
[7]Smith HW. The Kidney:Structure and function in health and disease [M], Oxford University Press, New York, USA,1951
[8]Brown SA. Evaluation of a single-injection method for estimating glomerular filtration rate in dogs with reduced renal function [J]. Am J Vet Res,1994,55:1470-1473
[9]Florjin KW, Barendregt JN, Lentjes EG, et al. Glomerular filtration rate measurement by "single-shot" injection of inulin [J]. Kidney Int,1994,46:252-259
[10]Heiene R, Moe L. Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog:a review [J]. J Vet Intern Med,1998,12:401-414
[11]Beutler HO. Inulin. HU Bergmeyer (Ed.), Methods of enzymatic analysis [M],3rd Ed., Vol. VI.1984, p. 41-45
[12]Degenaar CP, Frenken LAM, vHoff JP. Enzymatic method for determination of inulin [J]. Clin Chem, 1987,33:1070-1071
[13]Summerfield AL. Automated enzymatic analysis of inulin [J]. Clin Chem,1993,39:2333-2337
[14]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci 1998,64:151-156
[15]Braun JP, Lefebvre HP. Kidney Function and Damage. JJ Kaneko, JW Harvey, LB Michael (Eds.), Clinical Biochemistry of Domestic Animals [M],6th Ed., Academic Press, Elsevier Inc., California, USA, 2008, p.495-498
[1]Aminohippurate Sodium Injection. Product Datasheet Merck Sharp and Dohme, West Point PA, USA
[2]Schuster VL, Seldin DW. Renal clearance. DW Seldin, G Giebisch, The Kidney:Physiology and Pathophysiology,2nd Ed., Raven Press, New York, USA,1992, p.943-978
[3]Goldring W, Clarke RW, Smith HW. The phenol red clearance in normal man [J]. J Clin Invest,1936,15: 221
[4]Smith HW, Goldring W, Chasis H. The measurement of the tubular excretory mass, effective blood flow and filtration rate in the normal human kidney [J]. J Clin Invest,1938,17:263
[5]Goldring W, Chasis H, Ranges HA, et al. Relations of effective renal blood flow and glomerular filtration to tubular excretory mass in normal man [J]. J Clin Invest,1940,19:739
[6]Smith HW, Finkelstein N. Aliminosa L, et al. The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man [J]. J Clin Invest,1945,24:388
[7]Chasis H, Redish J, Goldring W, et al. The use of sodium p-aminohippurate for the functional evaluation of the human kidney [J]. J Clin West,1945,24:583-588
[8]Newman E, Kattus A, Genecin A, et al. Observations on the clearance method of determining renal plasma flow with diodrast, para-aminohippuric acid (PAH) and para-acetyl-aminohippuric acid (PACA) [J]. Bull John Hopkins Hosp,1949,84:135-168
[9]Tacket HS, Houck CR. Measurement of renal hemodynamics in man by the 'slope method' without urinalysis [J]. Proc Soc Exp Biol & Med,1950,74:317-321
[10]Mandel MJ, Vidt DQ Sapirstein LA. Disappearance of para-aminohippuric acid from the plasma of the dog after single intravenous injection [J]. Am J Physiol,1955,182 (3):428-432
[11]Parekh CK, Kirpan J, Peterson GL, et al. Automated simultaneous determination of p-aminohippurate and creatinine in plasma or urine [J]. Clin Chem,1974,20:348-352
[12]Preuss HG, Razzavi MH, Slemmer D, et al. Colorimetry of p-aminohippurate in the presence of sulfamethoxazole [J]. Clin Chem,1988,34 (2):422-423
[13]Schwartz LB, Gewertz BL, Bissell MG. Chemical assay of p-aminohippuric acid simplified by use of dimethylaminocinnamaldehyde in ethanol [J]. Clin Chem,1988,34(1):165
[14]Brenna S, Grigoras O, Drukker A, et al. Pitfalls in measuring inulin and para-amino-hippuric acid clearances [J]. Pediatr Nephrol,1998,12:489-491
[15]Laroute V, Lefebvre HP, Costes G, et al. Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and para-aminohippuric acid [J]. J Pharmacol Toxicol Methods,1999,41 (1):17-25
[16]Prescott LF, Freestone S, McAuslane JA. The concentration-dependent disposition of intravenous p-aminohippurate in subjects with normal and impaired renal function [J]. Br J Clin Phamacol,1993,35: 20-29
[17]Frindt G, Vial S. Conjugation of p-aminohippuric acid by human kidney and liver slices [J]. Acta Physiologica Latinamericana,1968,18:47-54
[18]Carpenter HM, Mudge GH. Uptake and acetylation of p-aminohippurate by slices of mouse kidney cortex [J]. J Pharmac Exp Ther,1980,213:350-354
[1]DiBartola SP. Renal Disease:Clinical Approach and Laboratory Evaluation. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,2005, p.1716-1730
[2]Nyland TG, Mattoon JS, Herrgesell EJ, et al. Urinary Tract. R Kersey, D LeMelledo (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., WB Saunders, Elsevier Inc., Philadelphia, USA.2002, p.158-195
[3]Peshin PK. Contrast materials and techniques. AP Singh, J Singh (Eds.), Veterinary Radiology [M],1st Ed., CBS Publishers. Delhi, India,1994, p.178-215
[4]Rawlings CA, Bjorling DE, Christie BA. Kidneys. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.1606-1619
[5]Holt PE. Radiographic Investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2008, p.14-23
[6]Wang A, Fudenberg HH. Heterogeneity of carbohydrate content of human 1gA Myeloma proteins [J]. Journal of Immunology.1970,105:1286-88
[7]Kimata S, Mizoguchi K, Hattori S, et al. Evaluation of a new automated, enzymatic inulin assay using D-fructose dehydrogenase [J]. Clin & Exper Nephrol,2009, Vol 13 (4):341-49
[8]Smith H W, Finkelstein N, Aliminosa L, et al. The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man [J]. J Clin Invest,1945,24:388
[1]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci,1998,64,151-56
[2]Laroute V, Lefebvre HP, Costes G, et al. Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and para-aminohippuric acid [J]. J Pharmacol Toxicol Methods,1999,41 (I):17-25
[3]Bright JM. lnterventional catheterization procedures. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.921-923
[4]Rawlings CA, Bjorling DE, Christie BA. Kidneys. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.1606-19
[1]Nyland TG， Mattoon JS, Herrgesell EJ, et al. Urinary Tract. R Kersey, D LeMelledo (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., Saunders, Elsevier Inc, Philadelphia, USA,2002, p.158-195
[2]Mattoon JS, Auld DM, Nyland TG. Abdominal ultrasound scanning techniques. TG Nyland, JS Mattoon (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., Saunders, USA,2002, p.49-81
[3]DiBartola SP. Renal Disease:Clinical Approach and Laboratory Evaluation. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., Saunders, Elsevier Inc., Philadelphia. USA, 2005, p.1716-1730
[4]Konde LJ, Wrigley RH, Park RD, et al. Ultrasonographic anatomy of the normal canine kidney [J]. Vet Radiol,1984,25:173-178
[5]Konde LJ. Park RD. Wrigley RH. et al. Comparison of radiography and ultrasonography in the evaluation of renal lesions in the dog [J]. J Am Vet Med,1986,188:1420-1425
[6]Wood AKW, McCarthy PH. Ultrasonographic-anatomic correlation and an imaging protocol of the normal canine kidney [J]. Am J Vet Res,1990,51:103-108
[7]Walter PA, Johnston GR, Feeney DA, et al. Renal ultrasonography in healthy cats [J]. Am J Vet Res.1987. 48:600-607
[8]Barr FJ. Evaluation of ultrasound as a method of assessing renal size in the dog [J]. J Small Anim Pract. 1990,31:174-179
[9]Barr FJ, Holt PE, Gibbs C. Ultrasonographic measurement of normal renal parameters [J]. J Small Anim Pract,1990,31:180-184
[1]Holt PE. Radiographic Investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2008, p.14-23
[2]Peshin PK. Contrast materials and techniques. AP Singh, J Singh (Eds.), Veterinary Radiology [M],1st Ed.. CBS Publishers, Delhi, India,1994, p.178-215
[3]Vegad JL, Katiyar AK. Urinary System. Textbook of Veterinary Systemic Pathology [M],1st Ed., International Book Distributing Co. Luknow, India,1998, p.205-235
[4]Kahn CM, Line S, Aiello SE. Urinary System. CM Kahn, S Line, SE Aiello (Eds.). The Merck Veterinary Manual [M],9th Ed., Merck and Co. Inc., Whitehouse Station, NJ, USA, 2005, p.1249-1287
[5]Ihle SL, Kostolich M. Acute renal failure associated with contrast medium administration in a dog [J]. JAm Vet Med,1991,199:899-901
[1]Holt PE. Radiographic Investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2008, p.14-23
[2]Rawlings CA, Bjorling DE, Christie BA. Kidneys. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA.2003, p.1606-1619
[3]Osborne CA. Techniques of urine collection and preservation. CA Osborne, DR Finco (Eds.), Canine and Feline Nephrology and Urology [M], Williams and Wilkins, Baltimore, USA, 1995, p.100-121
[4]Juan YS, Chuang SM, Wu WJ, et al. Evaluation of intra-renal blood flow by Doppler Ultrasonography immediately after extracorporeal shock wave lithotripsy on hydronephrotic kidney [J]. Kaohsiung J Med Sci,2005,21:412-417
[5]Tanji N, Yokoyama M, Terada N, et al. Renal tubular apoptosis after release of ureteral obstruction in the rat kidney [J]. Int J Urol,1998,5:256-261
[6]Wen JG, Frokiaer J, Jorgensen TM, et al. Obstructive nephropathy:an update of the experimental research [J]. Urol Res,1999,27:29-39
[7]Ishidoya S, Kaneto H, Fukuzaki A, et al. Pathophysiology and clinical implication of obstructive nephropathy [J]. Nippon Hinyokika Gakkai Zasshi,2003,94(7):645-55
[8]Zhou Y, Takahashi G, Shinagawa T, et al. Increased transforming growth factor-β1 and tubulointerstitial fibrosis in rats with congenital hydronephrosis [J]. Int J Urol,2002,9, 491-500
[1]Klahr S. Pathophysiology of obstructive nephropathy [J]. Kidney Int,1983,23:414-426
[2]Klahr S, Morrissey JJ. The role of growth factors, cytokines, and vasoactive compounds in obstructive nephropathy [J]. Semin Nephrol, 1998,18:622-632
[3]Sweeney P, Young L, Fitzpatrick J. An autoradiographic study of regional blood flow distribution in the rat kidney during ureteric obstruction—the role of vasoactive compounds [J]. BJU Int,2001,88: 268-272
[4]Rawashdeh YF, Horlyck A, Mortensen J, et al. Resistive index:an experimental study of acute complete unilateral ureteral obstruction [J]. Invest Radiol,2003,38:153-158
[5]Pelaez LI, Juncos LA, Stulak JM, et al. Non-invasive measurement of bilateral renal regional blood flow and tubular dynamics during acute ureteral obstruction [J]. Nephol Dial Transplant.2005,20: 83-88
[6]DiBartola SP. Clinical approach and laboratory evaluation of renal disease. SJ Ettinger. EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],4th Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,1995, p.1706-1719
[7]Gaspari F, Perico H, Remuzzi G. Measurement of glomerular filtration rate [J]. Kidney Int, 1997,52 suppl.63, p. S151-S154
[8]Finco DR, Brown SA, Crowell WA, et al. Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass [J]. Am J Vet Res,1991,52, 1029-1032
[9]Moe L, Heiene R. Estimation of glomerular filtration rate in dogs with 99M-Tc-DTPA and iohexol[J]. Res Vet Sci,1995,58,138-143
[10]Brown SA. Evaluation of a single-injection method for estimating glomerular filtration rate in dogs with reduced renal function [J]. Am J Vet Res,1994,55,1470-1473
[11]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci,1998,64,151-156
[12]Narins RG, Krishna GG, Riley LJ. Assessment of renal function:characteristics of the functional and organic forms of acute renal failure. D W Seldin, G Giebisch (Eds.), The Kidney:Physiology and Pathophysiology,2nd Ed, Raven Press, New York, USA,1992, p. 3063-3084
[13]Laroute V, Lefebvre HP, Costes G, et al. Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and para-aminohippuric acid [J]. J Pharmacol Toxicol Methods,1999,41 (1):17-25
[14]Gleadhill A, Michell AR. Evaluation of iohexol as a marker for the clinical measurement of glomerular filtration rate in dogs [J]. Res Vet Sci,1996,60,117-121
[15]Mandel MJ, Vidt DG, Sapirstein LA. Disappearance of Para-amino Hippuric Acid from the plasma of the dog after single intravenous injection [J]. Am J Physiol,1955,3:428-432
[16]Van Den Brom WE, Biewenga WJ. Assessment of glomerular filtration rate in normal dogs: analysis of the 5*Cr-EDTA clearance and its relation to several endogenous parameters of glomerular filtration [J]. Res Vet Sci,1981,30,152-157
[17]Grauer GF, DiBartola SP. Glomerular disease. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine,4th Ed, WB Saunders, Elsevier Inc., Philadelphia, USA,1995, p. 1760-1775
[18]Cowgill LD, Francey T. Acute Uremia. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],5th Ed, W B Saunders, Elsevier Inc., Philadelphia, USA, 2000, p.1731-1751
[19]Moody TE, Vaughan ED Jr, Gillenwater JY. Relationship between renal blood flow and ureteral pressure during 18 hours of total unilateral ureteral occlusion. Implications for changing sites of increased renal resistance [J]. Invest Urol,1975,13:246-251
[20]Shokeir AA, Nijman RJ, el-Azab M, et al. Partial ureteric obstruction:a study of Doppler ultrasonography and diuretic renography in different grades and durations of obstruction [J]. BrJ Urol,1996,78:829-835
[21]Estelberger W, Peter W, Zitta S, et al. Determination of the glomerular filtration rate by identification of sinistrin kinetics [J]. Eur J Clin Chem and Clin Biochem,1995,33,201-209
[1]Holt PE. Radiographic investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2005, p.14-23
[2]Stockham SL, Scott MA. Platelets. Fundamentals of Veterinary Clinical Pathology [M],2nd Ed., Blackwell Publishing Co., Iowa, USA,2008, p.223-257
[3]Meyer DJ, Harvey JW. Evaluation of erythrocyte disorders. L Fathman, J Gower (Eds.), Veterinary Laboratory Medicine-Interpretation and Diagnosis [M],3rd Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,2004, p.47-81
[4]Evans GO. Fluid balance, electrolytes, and mineral metabolism. GO Evans (Ed.), Animal Clinical Chemistry-A practical handbook for Toxicologists and Biomedical Researchers [M], 2nd Ed., CRC Press, Taylor and Francis Group, Florida, USA,2009, p.115-144
[5]Meyer DJ, Coles EH, Rich LJ. Electrolyte, acid-base homeostasis and disturbances. L Mills (Ed.), Veterinary Laboratory Medicine-Interpretation and Diagnosis [M],1st Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,1992, p.93-101
[6]Kahn CM, Line S, Aiello SE. Urinary System. CM Kahn, S Line, SE Aiello (Eds.), The Merck Veterinary Manual [M],9th Ed., Merck and Co. Inc., Whitehouse Station, NJ, USA, 2005, p.1249-1287
[2]Rytand DA. The number and size of mammalian glomeruli as related to kidney and body weight, with methods for their enumeration and measurement [J]. Am J Anat,1938,62 (4):507-520
[3]Vimtrup BJ. On the number, shape, structure, and surface area of the glomeruli in the kidneys of man and mammals [J]. Am J Anat,1928,41:123-151
[4]Brown SA, Barsanti JA, Finco DR. Determinants of glomerular ultrafiltration in cats [J]. Am J Vet Res. 1993,54:970-975
[5]Finco DR, Duncan JR. Relationship of glomerular number and diameter to body size of the dog [J]. Am J Vet Res,1972,33:2447-2450
[6]Gimonet V, Bussieres L, Medjebeur AA, et al. Nephrogenesis and angiotensin 11 receptor subtypes gene expression in the fetal lamb [J]. Am J Physiol,1998,274:F 1062-69
[7]Horster M, Kemler BJ, Valtin H. Intracortical distribution of number and volume of glomeruli during postnatal maturation in the dog [J]. J Clin Invest,1971.50:796-800
[8]Bankir L, de Rouffignac C. Urinary concentrating ability:insights from comparative anatomy [J]. Am J Physiol 1985,249:R 643-666
[9]Kriz W, Bankir L. A standard nomenclature for structures of the kidney. The renal Commission of the International Union of Physiological Sciences (IUPS) [J]. Kidney Int,1988,33:1-7
[10]Pallone TL, Silldorff EP, Turner MR. Intrarenal blood flow:microvascular anatomy and the regulation of medullary perfusion [J]. Clin Exp Pharmacol Physiol,1998,25:383-392
[11]Brown SA, Finco DR, Navar LG. Impaired renal autoregulatory ability in dogs with reduced renal mass [J]. J Am SocNephrol,1995,5:1768-1774
[12]Navar LG, Bell PD, White RW, et al. Evaluation of the single glomerular filtration coefficient in the dog [J]. Kidney Int,1977,12:137-149
[13]Tryggvason K. Unravelling the mechanism of glomerular filtration [J]. J Am Soc Nephroi,1999,10: 2440-2445
[14]Reilly RF, Ellison DH. Mammalian distal tubule:physiology, pathophysiology, and molecular anatomy [J]. Physiol Rev,2000,80:277-313
[15]Fisher JW. Erythropoietin:physiology and pharmacology update [J]. Exp Biol Med (Maywood),2003. 228:1-14
[16]Ebert R, Schutze N, Adamski J, et al. Vitamin D signaling is modulated on multiple levels in health and disease [J]. Mol Cell Endocrin,2006,248:149-159
[17]DiBartola SP. Renal Disease:Clinical approach and laboratory evaluation. SJ Ettinger and EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., Saunders, Elsevier Inc, Philadelphia, USA, 2005, p.1716-1730
[18]Cowgill LD, Francey T. Acute Uremia. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., Saunders, Elsevier Inc, Philadelphia, USA,2005, p.1731-1734
[19]Senior DF. Urinary Disorders. Michael S (Ed.), Clinical medicine of the Dog and Cat [M],2nd Ed.. Manson Publishing Ltd. (The Veterinary Press),2003, p.409-453
[20]Kahn CM, Line S, Aiello SE. Urinary System. CM Kahn, S Line, SE Aiello (Eds.), The Merck Veterinary Manual [M],9th Ed., Merck and Co. Inc., Whitehouse Station, NJ, USA,2005, p.1249-1287
[21]Vegad JL, Katiyar AK. Urinary System. Textbook of Veterinary Systemic Pathology [M], 1st Ed., International Book Distributing Company, Lucknow, India,1998, p.226-227
[22]Brown SA. Pathophysiology and Therapeutics of Urinary Tract Diseases. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA.2003, p.1583-1594
[23]Braun JP, Lefebvre HP. Kidney Function and Damage. JJ Kaneko, JW Harvey, LB Michael (Eds.), Clinical Biochemistry of Domestic Animals [M],6th Ed., Academic Press, Elsevier Inc., California, USA, 2008, p.490-510
[24]Park R, Rabinowitz L. Effect of reduced glomerular filtration rate on the fractional excretion of urea in the dog [J]. Proc Soc Exp Biol Med,1969,132:27-29
[25]Nyland TQ Mattoon JS, Herrgesell EJ, et al. Urinary Tract. R Kersey, D LeMelledo (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., Saunders, Elsevier Inc., Philadelphia, USA,2002, p.158-195
[26]Rawlings AC, Bjorling DE, Christie BA. Principles of Urinary Tract Surgery. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.1594-1606
[27]Wood AKW, McCarthy PH. Ultrasonographic-anatomic correlation and an imaging protocol of the normal canine kidney [J]. Am J Vet Res 1990,51:103-108
[28]Yeager AE, Anderson Wl. Study of association between histologic features and echogenicity of architecturally normal cat kidneys [J]. Am J Vet Res,1989,50:860-863
[29]Biller DS, Kantrowitz B, Partington BP, et al. Diagnostic ultrasound of the urinary bladder [J]. J Am Anim HospAssoc,1990,26:397-402
[30]Pugh CR, Arger PH, Sehgal CM. Power, spectral, and color flow Doppler enhancement by a new ultrasonographic contrast agent [J]. J Ultrasound Med,1996,15(12):843-852
[31]Barr FJ. Evaluation of ultrasound as a method of assessing renal size in the dog [J]. J Small Anim Pract 1990,31:174-179
[32]Walter PA, Feeney DA, Johnston GR, et al. Feline renal ultrasonography:quantitative analyses of imaged anatomy [J]. Am J Vet Res,1987,48 (4):596-599
[33]Hager DA, Nyland TG, Fisher P. Ultrasound-guided biopsy of the canine liver, kidney, and prostate [J] Vet Radiol,1985,26 (3):82-88
[34]Konde LJ, Wrigley RH, Park RD, et al. Ultrasonographic anatomy of the normal canine kidney [J]. Vet Radiol,1984,25:173-178
[35]Walter PA, Feeney DA, Johnston GR, et al. Ultrasonographic evaluation of renal parenchymal diseases in dogs:32 cases (1981-1986) [J].J Am Vet Med Assoc,1987,191:999-1007
[36]Nyland TG, Fisher PE, Gregory CR, et al. Ultrasonographic evaluation of renal size in dogs with acute allograft rejection [J]. Vet Radiol Ultrasound,1997,38:55-61
[37]Pollard R, Nyland TG, Bernsteen L, et al. Ultrasonographic evaluation of renal autografts in normal cats [J]. Vet Radiol Ultrasound,1999,40 (4):380-385
[38]Peshin PK. Contrast materials and techniques. AP Singh (Ed.), Veterinary Radiology [M],1st Ed., CBS Publishers and Distributors, Delhi, India,1994, p.178-215
[39]Johnston GR, Walter PA, Feeney DA. Diagnostic imaging of the urinary tract CA Osborne, DR Finco (Eds.), Canine and Feline Nephrology and Urology [M], Ist Ed., Williams & Wilkins, Baltimore, USA, 1995, p.230-276
[40]Lord PF, Scott RC, Chan KF, et al. Intravenous urography for evaluation of renal diseases in small animals [J]. J Am Anim Hosp Assoc,1974,10:139
[41]Pechman RD. Urinary trauma in dogs and cats:a review [J]. J Am Anim Hosp Assoc,1982,18:33
[42]Feeney DA, Thrall DE, Barber DL, et al. Normal canine urogram:effects of dose, time, and individual dog variation [J]. Am J Vet Res,1979,40 (11):1596-604
[43]Feeney DA, et al. The excretory urogram. Parts Ⅰ and Ⅱ [J]. Compend Contin Educ Pract Vet,1982,4:233
[44]Thornhill JA, Cechner PE. Traumatic injuries to the kidneys, ureter, bladder and urethra [J]. Vet Clin North Am,1981,11:157
[45]Ihle SL, Kostolich M. Acute renal failure associated with contrast medium administration in a dog [J]. J Am Vet Med,1991,199:899-901
[46]Rivers BJ, Walter PA, Polzin DJ. Ultrasonographic-guided, percutaneous antegrade pyelography: technique and clinical application in the dog and cat [J]. J Am Anim Hosp Assoc,1997,33:61-68
[47]Bricker NS, Morrin PA, Kime SW, Jr. The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis" [J]. J Am Soc Nephrol,1997,8:1470-1476
[48]Swaminathan R, Major P, Sneider H, et al. Serum creatinine and fat-free mass (lean body mass) [J]. CJin Chem,2000,46:1695-1696
[49]Price GS, Frazier DL. Use of body surface area (BSA)-based dosages to calculate chemotherapeutic drug dos in dogs:1. potential problems with current BSA formulae [J]. J Vet Intern Med,1998,12:267-271
[50]Peters AM, Henderson BL, Lui D. Indexed glomerular filtration rate as a function of age and body size [J]. Clin Sci,2000,98:439-444
[51]Gleadhill A. Evaluation of screening tests for renal insufficiency in the dog [J]. J Small anim Pract,1994, 35:391-396
[52]Gleadhill A, Michell AR. Evaluation of iohexol as a marker for the clinical measurement of glomerular filtration rate in dogs [J]. Res Vet Sci,1996,60:117-121
[53]Grubb A, Nordin G. Notable steps in obtaining improved estimates for glomerular filtration rate [J}. CJin Chem,2006,52:169-170
[54]Finco DR, Brown SA, Vaden SL, et al. Relationship between plasma creatinine concentration and glomerular filtration rate in dogs [J]. J Vet Pharmacol Ther,1995,18:418-421
[55]Heiene R, Moe L. Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog:a review [J]. J Vet Intern Med,1998,12:401-414
[56]Shannon JA. The excretion of inulin in the dog [J]. Am J Physiol,1935,112:405-413
[57]Watson AD, Lefebvre HP, Concordet D, et al. Plasma exogenous creatinine clearance test in dogs: comparison with other methods and proposed limited sampling strategy [J]. J Vet Intern Med,2002a,16: 22-23
[58]Osborne CA. Techniques of urine collection and preservation. CA Osborne, DR Finco (Eds.), Canine and Feline Nephrology and Urology [M], Williams and Wilkins, Baltimore, USA,1995, p.100-121
[59]Ladd M, Liddle L, Gagnon JA. Renal excretion of inulin, creatinine, and ferrocyanide, at normal and reduced clearance levels in the dog [J]. Am J Physiol,1956,184:505-514
[60]Bing J, Effersoe P. Comparative tests of the thiosulphate and creatinine clearance in rabbits and cats [J]. Acta Physiol Scand,1948,15:231-236
[61]Dalton RG. Renal function in neonatal calves:inulin, thiosulphate, and para-aminohippuric acid clearance [J]. BrVet J,1968,124:498-502
[62]Maddison JE, Pascoe PJ, Jansen BS. Clinical evaluation of sodium sulfanilate clearance for the diagnosis of renal disease in dogs [J]. J Am Vet Med Assoc,1984,185:961-965
[63]Ross LA, Finco DR. Relationship of selected clinical renal function tests to glomerular filtration rate and renal blood flow in cats [J]. Am J Vet Res,1981,42:1704-1710
[64]Bovee KC, Joyce T. Clinical evaluation of glomerular function:24-hour creatinine clearance in dogs [J]. J Am Vet Med Assoc,1979,174:488-491
[65]Finco DR, Coulter DB, Barsanti JA. Simple, accurate method for clinical estimation of glomerular filtration rate in the dog [J]. Am J Vet Res,1981,42:1874-1877
[66]Finco DR, Brown SA, Crowell WA, et al. Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass [J]. Am J Vet Res 1991,52:1029-1032
[67]Moe L, Heiene R. Estimation of glomerular filtration rate in dogs with 99M-Tc-DTPA and iohexol [J]. Res Vet Sci,1995,58:138-143
[68]Brown SA, Finco DR, Boudinot FD, et al. Evaluation of a single-injection method, using iohexol, for estimating glomerular filtration rate in cats and dogs [J]. Am J Vet Res 1996,57:105-110
[69]Drost WT, Henry GA, Meinkoth JH, et al. The effects of a unilateral ultrasound-guided renal biopsy on renal function in healthy sedated cats [J]. Vet Radiol Ultrasound,2000,41:57-62
[70]Uribe D, Krawiec DR, Twardock AR. Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc-diethylenetriaminepentaacetic acid [J]. Am J Vet Res 1992,53:1101-1107
[71]Daniel GB, Mitchell SK, Mawby D. Renal nuclear medicine:a review [J] Vet Radiol Ultrasound.1999, 40:572-587
[72]Biwenga WJ, van den Brom WE. Assessment of glornerular filtration rate in dogs with renal insufficiency: analysis of the 51Cr-EDTA clearanace and its relation to the plasma concentrations of urea and creatinine [J]. Res Vet Sci,1981,30:158-160
[73]Matthews HK, Andrews FM, Daniel GB, et al. Comparison of standard and radionuclide methods for measurement of glomerular filtration rate and effective renal blood flow in female horses [J]. Am J Vet Res,1992,53:1612-1616
[74]Walsh DM, Royal HD. Evaluation of a single injection of 99m-Tc-Iabeled diethylenetraminepentaacetic acid for measuring glomerular filtration rate in horses [J]. Am J Vet Res,1992,53:776-780
[75]Pihl B, Nosslin B. The single injection technique for determination of renal clearance. I. clearance of iothalamate and iodohippurate in dogs [J]. Scan J Urol Nephrol,1974,8:138-146
[76]Summerville DA, Treves ST. Single plasma sample technique of glomerular filtration rate measurement [J]. J Nucl Med Allied Sci,1986,30:177-184
[77]Brown SA, Haberman C, Finco DR. Use of plasma clearance of inulin for estimating glomerular filtration rate in cats [J]. Am J Vet Res,1996,57:1702-1705
[78]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci,1998,64:151-156
[79]Barthez PY, Hornof WJ, Cowgill LD, et al. Comparison between the scintigraphic uptake and plasma clearance of 99mTc-diethylenetriamine penta-acetic acid (DTPA) for the evaluation of the glomerular filtration rate in dogs [J]. Vet Radiol Ultrasound,1998,39:470-474
[80]Kampa N, Wennstrom U, Lord P, et al. Effect of region of interest selection and uptake measurement on glomerular filtration rate measured by 99mTc-DTPA scintigraphy in dogs [J]. Vet Radiol Ultrasound, 2002,43 (4):383-391
[81]Krawiec DR, Badertscher RR 2nd, Twardock AR, et al. Evaluation of 99mTc-diethylenetriamine penta-acetic acid nuclear imaging for quantitative determination of glomerular filtration rate of dogs [J]. Am J Vet Res 1986,47 (10):2175-2179
[82]Rogers KS, Komkov A, Brown SA, et al. Comparison of four methods of estimating the glomerular filtration rate in cats [J]. Am J Vet Res,1991,52 (6):961-964
[83]Finco DR. Measurement of glomerular filtration rate via urinary clearance of inulin and plasma clearance of Tc99th penetate and exogenous creattnine in dogs [J]. Am J Vet Res,2005,66:1046-1055
[84]Gagnon JA, Schrier RW, Weis TP, et al. Clearance of iothalamate-125 I as a measure of glomerular filtration rate in the dog [J]. J Appl Physiol,1971,30:774-778
[85]Izzat NN, Rosborough JP. Renal function in conscious dogs:potential effect of gender on measurement [J]. Res Exp Med,1989,189:371-379
[86]Miyamoto K. Use of plasma clearance of iohexol for estimating glomerular filtration rate in cats [J]. Am J Vet Res,2001b,62:572-575
[87]Fettman MJ, Allen TA, Wilke WL, et al. Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats [J]. Am J Vet Res,1985,46:482-485
[88]Thrall MA. Laboratory evaluation of renal function. DB Troy (Ed.), Veterinary Hematology and Clinical Chemistry [M], Lippincott Williams and Wilkins, Baltimore, USA,2004, p:7:91
[89]Marks PW, Rosovsky R. Hematologic manifestations of systemic disease:Liver and Renal Disease. R Hoffman, EJ Benz Jr., SJ Shattil, B Furie, LE Silberstein, P McGlave, H Heslop (Eds.), Hematology: Basic Principles and Practice [M],5th Ed., Churchill Livingstone, An imprint of Elsevier Inc., USA,2008, p.2303-2308
[90]Hocking WG. Hematologic abnormalities in patients with renal diseases [J]. Hematol Oncol Clin North Am 1987,1(2):229-260
[91]Schiller GJ, Berkman SA. Hematologic aspects of renal insufficiency [J]. Blood Rev,1989,3(3):141-6
[92]Thrall MA. Non-regenerative anemia. DB Troy (Ed.), Veterinary Hematology and Clinical Chemistry [M], Lippincott Williams and Wilkins, Baltimore, USA,2004, p.89-93
[93]Fried W. Hematologic complications of chronic renal failure [J]. Med Clin North Am,1978,62(6): 1363-79
[94]Naets JP. Hematologic disorders in renal failure [J]. Nephron,1975,14(2):181-94
[95]Radin MJ. Interpretation of Biochemical Profiles. W R Fenner (Ed.), Quick reference to Veterinary Medicine [M],3rd Ed. Wiley-Blackwell Publishing Co.,2000, p.166-176
[96]Wen JG, Frokiaer J, Jorgensen TM, et al. Obstructive nephropathy:an update of the experimental research [J]. Urol Res,1999,27:29-39
[97]Zhou Y, Takahashi G, Shinagawa T, et al. Increased transforming growth factor-β1 and tubulointerstitial fibrosis in rats with congenital hydronephrosis [J]. Int J Urol 2002,9:491-500
[98]Tanji N. Yokoyama M, Terada N, et al. Renal tubular apoptosis after release of ureteral obstruction in the rat kidney [J]. Int J Urol,1998,5:256-261
[1]Barbour GL, Crumb CK, Boyd CM. et al. Comparison of inulin, iothalamate, and 99mTc-DTPA for measurement of glomerular filtration rate [J]. J Nuc Med,1976,17 (4):317-320
[2]Kim EK, Onesti G, Ramirez O. et al. Creatinine clearance in renal disease. A reappraisal [J]. Brit Med J, 1969,4:11-14
[3]Luippold G, Schneider S, Stefanescu A, et al. Dopamine D2-like receptors and amino acid-induced glomerular hyperfiltration in humans [J]. Brit J Clin Pharm,2001.51 (5):415-421
[4]Finco DR, Brown SA, Crowelf WA, et al. Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass [J]. Am J Vet Res,1991,52:1029-1032
[5]Moe L, Heiene R. Estimation of glomerular filtration rate in dogs with 99mTc-DTPA and iohexol [J]. Res Vet Sci,1995,58:138-143
[6]Gleadhill A, Peters AM, Michell AR. A simple method for measuring glomerular filtration rate in dogs [J]. Res VetSci,1995,59:118-123
[7]Smith HW. The Kidney:Structure and function in health and disease [M], Oxford University Press, New York, USA,1951
[8]Brown SA. Evaluation of a single-injection method for estimating glomerular filtration rate in dogs with reduced renal function [J]. Am J Vet Res,1994,55:1470-1473
[9]Florjin KW, Barendregt JN, Lentjes EG, et al. Glomerular filtration rate measurement by "single-shot" injection of inulin [J]. Kidney Int,1994,46:252-259
[10]Heiene R, Moe L. Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog:a review [J]. J Vet Intern Med,1998,12:401-414
[11]Beutler HO. Inulin. HU Bergmeyer (Ed.), Methods of enzymatic analysis [M],3rd Ed., Vol. VI.1984, p. 41-45
[12]Degenaar CP, Frenken LAM, vHoff JP. Enzymatic method for determination of inulin [J]. Clin Chem, 1987,33:1070-1071
[13]Summerfield AL. Automated enzymatic analysis of inulin [J]. Clin Chem,1993,39:2333-2337
[14]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci 1998,64:151-156
[15]Braun JP, Lefebvre HP. Kidney Function and Damage. JJ Kaneko, JW Harvey, LB Michael (Eds.), Clinical Biochemistry of Domestic Animals [M],6th Ed., Academic Press, Elsevier Inc., California, USA, 2008, p.495-498
[1]Aminohippurate Sodium Injection. Product Datasheet Merck Sharp and Dohme, West Point PA, USA
[2]Schuster VL, Seldin DW. Renal clearance. DW Seldin, G Giebisch, The Kidney:Physiology and Pathophysiology,2nd Ed., Raven Press, New York, USA,1992, p.943-978
[3]Goldring W, Clarke RW, Smith HW. The phenol red clearance in normal man [J]. J Clin Invest,1936,15: 221
[4]Smith HW, Goldring W, Chasis H. The measurement of the tubular excretory mass, effective blood flow and filtration rate in the normal human kidney [J]. J Clin Invest,1938,17:263
[5]Goldring W, Chasis H, Ranges HA, et al. Relations of effective renal blood flow and glomerular filtration to tubular excretory mass in normal man [J]. J Clin Invest,1940,19:739
[6]Smith HW, Finkelstein N. Aliminosa L, et al. The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man [J]. J Clin Invest,1945,24:388
[7]Chasis H, Redish J, Goldring W, et al. The use of sodium p-aminohippurate for the functional evaluation of the human kidney [J]. J Clin West,1945,24:583-588
[8]Newman E, Kattus A, Genecin A, et al. Observations on the clearance method of determining renal plasma flow with diodrast, para-aminohippuric acid (PAH) and para-acetyl-aminohippuric acid (PACA) [J]. Bull John Hopkins Hosp,1949,84:135-168
[9]Tacket HS, Houck CR. Measurement of renal hemodynamics in man by the 'slope method' without urinalysis [J]. Proc Soc Exp Biol & Med,1950,74:317-321
[10]Mandel MJ, Vidt DQ Sapirstein LA. Disappearance of para-aminohippuric acid from the plasma of the dog after single intravenous injection [J]. Am J Physiol,1955,182 (3):428-432
[11]Parekh CK, Kirpan J, Peterson GL, et al. Automated simultaneous determination of p-aminohippurate and creatinine in plasma or urine [J]. Clin Chem,1974,20:348-352
[12]Preuss HG, Razzavi MH, Slemmer D, et al. Colorimetry of p-aminohippurate in the presence of sulfamethoxazole [J]. Clin Chem,1988,34 (2):422-423
[13]Schwartz LB, Gewertz BL, Bissell MG. Chemical assay of p-aminohippuric acid simplified by use of dimethylaminocinnamaldehyde in ethanol [J]. Clin Chem,1988,34(1):165
[14]Brenna S, Grigoras O, Drukker A, et al. Pitfalls in measuring inulin and para-amino-hippuric acid clearances [J]. Pediatr Nephrol,1998,12:489-491
[15]Laroute V, Lefebvre HP, Costes G, et al. Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and para-aminohippuric acid [J]. J Pharmacol Toxicol Methods,1999,41 (1):17-25
[16]Prescott LF, Freestone S, McAuslane JA. The concentration-dependent disposition of intravenous p-aminohippurate in subjects with normal and impaired renal function [J]. Br J Clin Phamacol,1993,35: 20-29
[17]Frindt G, Vial S. Conjugation of p-aminohippuric acid by human kidney and liver slices [J]. Acta Physiologica Latinamericana,1968,18:47-54
[18]Carpenter HM, Mudge GH. Uptake and acetylation of p-aminohippurate by slices of mouse kidney cortex [J]. J Pharmac Exp Ther,1980,213:350-354
[1]DiBartola SP. Renal Disease:Clinical Approach and Laboratory Evaluation. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,2005, p.1716-1730
[2]Nyland TG, Mattoon JS, Herrgesell EJ, et al. Urinary Tract. R Kersey, D LeMelledo (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., WB Saunders, Elsevier Inc., Philadelphia, USA.2002, p.158-195
[3]Peshin PK. Contrast materials and techniques. AP Singh, J Singh (Eds.), Veterinary Radiology [M],1st Ed., CBS Publishers. Delhi, India,1994, p.178-215
[4]Rawlings CA, Bjorling DE, Christie BA. Kidneys. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.1606-1619
[5]Holt PE. Radiographic Investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2008, p.14-23
[6]Wang A, Fudenberg HH. Heterogeneity of carbohydrate content of human 1gA Myeloma proteins [J]. Journal of Immunology.1970,105:1286-88
[7]Kimata S, Mizoguchi K, Hattori S, et al. Evaluation of a new automated, enzymatic inulin assay using D-fructose dehydrogenase [J]. Clin & Exper Nephrol,2009, Vol 13 (4):341-49
[8]Smith H W, Finkelstein N, Aliminosa L, et al. The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man [J]. J Clin Invest,1945,24:388
[1]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci,1998,64,151-56
[2]Laroute V, Lefebvre HP, Costes G, et al. Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and para-aminohippuric acid [J]. J Pharmacol Toxicol Methods,1999,41 (I):17-25
[3]Bright JM. lnterventional catheterization procedures. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.921-923
[4]Rawlings CA, Bjorling DE, Christie BA. Kidneys. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA,2003, p.1606-19
[1]Nyland TG， Mattoon JS, Herrgesell EJ, et al. Urinary Tract. R Kersey, D LeMelledo (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., Saunders, Elsevier Inc, Philadelphia, USA,2002, p.158-195
[2]Mattoon JS, Auld DM, Nyland TG. Abdominal ultrasound scanning techniques. TG Nyland, JS Mattoon (Eds.), Small Animal Diagnostic Ultrasound [M],2nd Ed., Saunders, USA,2002, p.49-81
[3]DiBartola SP. Renal Disease:Clinical Approach and Laboratory Evaluation. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],6th Ed., Saunders, Elsevier Inc., Philadelphia. USA, 2005, p.1716-1730
[4]Konde LJ, Wrigley RH, Park RD, et al. Ultrasonographic anatomy of the normal canine kidney [J]. Vet Radiol,1984,25:173-178
[5]Konde LJ. Park RD. Wrigley RH. et al. Comparison of radiography and ultrasonography in the evaluation of renal lesions in the dog [J]. J Am Vet Med,1986,188:1420-1425
[6]Wood AKW, McCarthy PH. Ultrasonographic-anatomic correlation and an imaging protocol of the normal canine kidney [J]. Am J Vet Res,1990,51:103-108
[7]Walter PA, Johnston GR, Feeney DA, et al. Renal ultrasonography in healthy cats [J]. Am J Vet Res.1987. 48:600-607
[8]Barr FJ. Evaluation of ultrasound as a method of assessing renal size in the dog [J]. J Small Anim Pract. 1990,31:174-179
[9]Barr FJ, Holt PE, Gibbs C. Ultrasonographic measurement of normal renal parameters [J]. J Small Anim Pract,1990,31:180-184
[1]Holt PE. Radiographic Investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2008, p.14-23
[2]Peshin PK. Contrast materials and techniques. AP Singh, J Singh (Eds.), Veterinary Radiology [M],1st Ed.. CBS Publishers, Delhi, India,1994, p.178-215
[3]Vegad JL, Katiyar AK. Urinary System. Textbook of Veterinary Systemic Pathology [M],1st Ed., International Book Distributing Co. Luknow, India,1998, p.205-235
[4]Kahn CM, Line S, Aiello SE. Urinary System. CM Kahn, S Line, SE Aiello (Eds.). The Merck Veterinary Manual [M],9th Ed., Merck and Co. Inc., Whitehouse Station, NJ, USA, 2005, p.1249-1287
[5]Ihle SL, Kostolich M. Acute renal failure associated with contrast medium administration in a dog [J]. JAm Vet Med,1991,199:899-901
[1]Holt PE. Radiographic Investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2008, p.14-23
[2]Rawlings CA, Bjorling DE, Christie BA. Kidneys. D Slatter (Ed.), Textbook of Small Animal Surgery [M],3rd Ed., Saunders, USA.2003, p.1606-1619
[3]Osborne CA. Techniques of urine collection and preservation. CA Osborne, DR Finco (Eds.), Canine and Feline Nephrology and Urology [M], Williams and Wilkins, Baltimore, USA, 1995, p.100-121
[4]Juan YS, Chuang SM, Wu WJ, et al. Evaluation of intra-renal blood flow by Doppler Ultrasonography immediately after extracorporeal shock wave lithotripsy on hydronephrotic kidney [J]. Kaohsiung J Med Sci,2005,21:412-417
[5]Tanji N, Yokoyama M, Terada N, et al. Renal tubular apoptosis after release of ureteral obstruction in the rat kidney [J]. Int J Urol,1998,5:256-261
[6]Wen JG, Frokiaer J, Jorgensen TM, et al. Obstructive nephropathy:an update of the experimental research [J]. Urol Res,1999,27:29-39
[7]Ishidoya S, Kaneto H, Fukuzaki A, et al. Pathophysiology and clinical implication of obstructive nephropathy [J]. Nippon Hinyokika Gakkai Zasshi,2003,94(7):645-55
[8]Zhou Y, Takahashi G, Shinagawa T, et al. Increased transforming growth factor-β1 and tubulointerstitial fibrosis in rats with congenital hydronephrosis [J]. Int J Urol,2002,9, 491-500
[1]Klahr S. Pathophysiology of obstructive nephropathy [J]. Kidney Int,1983,23:414-426
[2]Klahr S, Morrissey JJ. The role of growth factors, cytokines, and vasoactive compounds in obstructive nephropathy [J]. Semin Nephrol, 1998,18:622-632
[3]Sweeney P, Young L, Fitzpatrick J. An autoradiographic study of regional blood flow distribution in the rat kidney during ureteric obstruction—the role of vasoactive compounds [J]. BJU Int,2001,88: 268-272
[4]Rawashdeh YF, Horlyck A, Mortensen J, et al. Resistive index:an experimental study of acute complete unilateral ureteral obstruction [J]. Invest Radiol,2003,38:153-158
[5]Pelaez LI, Juncos LA, Stulak JM, et al. Non-invasive measurement of bilateral renal regional blood flow and tubular dynamics during acute ureteral obstruction [J]. Nephol Dial Transplant.2005,20: 83-88
[6]DiBartola SP. Clinical approach and laboratory evaluation of renal disease. SJ Ettinger. EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],4th Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,1995, p.1706-1719
[7]Gaspari F, Perico H, Remuzzi G. Measurement of glomerular filtration rate [J]. Kidney Int, 1997,52 suppl.63, p. S151-S154
[8]Finco DR, Brown SA, Crowell WA, et al. Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass [J]. Am J Vet Res,1991,52, 1029-1032
[9]Moe L, Heiene R. Estimation of glomerular filtration rate in dogs with 99M-Tc-DTPA and iohexol[J]. Res Vet Sci,1995,58,138-143
[10]Brown SA. Evaluation of a single-injection method for estimating glomerular filtration rate in dogs with reduced renal function [J]. Am J Vet Res,1994,55,1470-1473
[11]Haller M, Muller W, Binder H, et al. Single-injection inulin clearance:a simple method for measuring glomerular filtration rate in dogs [J]. Res Vet Sci,1998,64,151-156
[12]Narins RG, Krishna GG, Riley LJ. Assessment of renal function:characteristics of the functional and organic forms of acute renal failure. D W Seldin, G Giebisch (Eds.), The Kidney:Physiology and Pathophysiology,2nd Ed, Raven Press, New York, USA,1992, p. 3063-3084
[13]Laroute V, Lefebvre HP, Costes G, et al. Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and para-aminohippuric acid [J]. J Pharmacol Toxicol Methods,1999,41 (1):17-25
[14]Gleadhill A, Michell AR. Evaluation of iohexol as a marker for the clinical measurement of glomerular filtration rate in dogs [J]. Res Vet Sci,1996,60,117-121
[15]Mandel MJ, Vidt DG, Sapirstein LA. Disappearance of Para-amino Hippuric Acid from the plasma of the dog after single intravenous injection [J]. Am J Physiol,1955,3:428-432
[16]Van Den Brom WE, Biewenga WJ. Assessment of glomerular filtration rate in normal dogs: analysis of the 5*Cr-EDTA clearance and its relation to several endogenous parameters of glomerular filtration [J]. Res Vet Sci,1981,30,152-157
[17]Grauer GF, DiBartola SP. Glomerular disease. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine,4th Ed, WB Saunders, Elsevier Inc., Philadelphia, USA,1995, p. 1760-1775
[18]Cowgill LD, Francey T. Acute Uremia. SJ Ettinger, EC Feldman (Eds.), Textbook of Veterinary Internal Medicine [M],5th Ed, W B Saunders, Elsevier Inc., Philadelphia, USA, 2000, p.1731-1751
[19]Moody TE, Vaughan ED Jr, Gillenwater JY. Relationship between renal blood flow and ureteral pressure during 18 hours of total unilateral ureteral occlusion. Implications for changing sites of increased renal resistance [J]. Invest Urol,1975,13:246-251
[20]Shokeir AA, Nijman RJ, el-Azab M, et al. Partial ureteric obstruction:a study of Doppler ultrasonography and diuretic renography in different grades and durations of obstruction [J]. BrJ Urol,1996,78:829-835
[21]Estelberger W, Peter W, Zitta S, et al. Determination of the glomerular filtration rate by identification of sinistrin kinetics [J]. Eur J Clin Chem and Clin Biochem,1995,33,201-209
[1]Holt PE. Radiographic investigations. J Northcott, P Beynon (Eds.), Urological Disorders of the Dog and cat:investigation, diagnosis and treatment [M], Manson Publishing Ltd., The Veterinary Press, London, UK,2005, p.14-23
[2]Stockham SL, Scott MA. Platelets. Fundamentals of Veterinary Clinical Pathology [M],2nd Ed., Blackwell Publishing Co., Iowa, USA,2008, p.223-257
[3]Meyer DJ, Harvey JW. Evaluation of erythrocyte disorders. L Fathman, J Gower (Eds.), Veterinary Laboratory Medicine-Interpretation and Diagnosis [M],3rd Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,2004, p.47-81
[4]Evans GO. Fluid balance, electrolytes, and mineral metabolism. GO Evans (Ed.), Animal Clinical Chemistry-A practical handbook for Toxicologists and Biomedical Researchers [M], 2nd Ed., CRC Press, Taylor and Francis Group, Florida, USA,2009, p.115-144
[5]Meyer DJ, Coles EH, Rich LJ. Electrolyte, acid-base homeostasis and disturbances. L Mills (Ed.), Veterinary Laboratory Medicine-Interpretation and Diagnosis [M],1st Ed., WB Saunders, Elsevier Inc., Philadelphia, USA,1992, p.93-101
[6]Kahn CM, Line S, Aiello SE. Urinary System. CM Kahn, S Line, SE Aiello (Eds.), The Merck Veterinary Manual [M],9th Ed., Merck and Co. Inc., Whitehouse Station, NJ, USA, 2005, p.1249-1287