泌尿外科疾病尿酶变化的动物实验及临床应用系列研究

肾实质损害必将在各种尿酶变化上反映出来,为证实此点,近5年间选择几种泌尿外科疾病进行了系列动物实验研究及临床验证,包括:①调整尿样与基质液量间1:5比例、加用反应终止剂后测定尿丙氨酸氨基肽酶的手工操作新方法,结果稳定、精确、重复性好.对其他尿酶检测,尿样也经超滤、透析等预处理,清除酶抑制物,务使结果精确.②采用典型的动物模型,动态观测肾血管性高血压的尿酶酶谱变化,高血压形成后4～8周,尿AAP、NAG持续升高,GGT早期升高后期下降.15例确诊病例的酶变化与动物模型相符.③肾细胞癌早期即显示尿酶异常:AAP、NAG显著增高,GGT降低,LDH受血尿影响而不稳定.15例经影像学及手术确诊者的阳性率为14/15.④犬庆大霉素肾毒模型实验,治疗剂量1～3d后对肾毒作用即从4种尿酶值变化中反映出来,中毒量及亚临床期肾病可加重加速肾损害,较肌酐值升高提早2～7d.动态监测出的强、弱尿酶反应曲线是肾存在病变的重要指标.77例庆大霉素治疗病人的尿酶变化与实验结果相同.⑤30例体外震波碎石后尿酶值升高证明其对肾实质的损害作用,此种损害一般方法不能测知.⑥异体肾移植中肾断流、再灌注均可由自由基引起肾细胞损害,肾移植后尿酶监测是诊断排斥反应、判定抗排斥治疗效果及预后的重要指标.在实验模型及51例病人中均获     

庆大霉素肾损害尿酶活性测定的意义

尿酶N乙酰β氨基葡萄糖苷酶(NAG)、尿磷酸二酯酶(PDEI)是近年来用以反映肾损害较敏感的指标。我们对庆大霉素肾损害的尿酶改变进行了观察,发现用药后显著高于用药前,检测尿NAG、PDEI可早期发现庆大霉素肾毒性。1　对象和方法1.1　对象　选择18～50岁年龄组30例。经常规检查尿常规、血清尿素氮(BUN)、血肌酐(Cr)及肾脏B超均在正常范围内,排除肾脏疾病,一般情况好。分为庆大霉素组18例,抗感染治疗,予庆大霉素24万U静滴,连用5d。青霉素组12例,剂量400万U静滴,连用5d。1.2　标本与试剂　收集任意中段尿液,室温或4℃保存,48h内检测。尿…     

尿AAP、NAG、GGT测定早期诊断庆大霉素肾脏损害的临床观察

本文系统观察了75例庆大霉素治疗的病人尿AAP、NAG、GGT的变化。用药后1～3天,尿AAP、NAG显著性升高,GGT中等度升高;而尿常规检查阴性。肾功能正常者,用药后血肌酐变化无统计学差异,仅2例肌酐升高值≥50μmol/L,占7.4％。处于亚临床期肾病变者,用药7天后,血肌酐升高,有8例其升高值≥50μmol/L,为47.1％。尿酶升高的时间早于血肌酐5～7天,是早期诊断庆大霉素肾脏损害的灵敏指标。     

冬虫夏草防治氨基糖甙急性肾损害的机理研究

本研究动态观察了冬虫夏草对氨基糖甙肾毒性损伤大鼠尿及肾组织中EGF变化的影响.将SD雄性大鼠随机分为二组:庆大霉素组和庆大 冬虫夏草组。所有动物接受庆大霉素160(mg/kg)/d腹腔注射,而庆大 虫草组同时给冬虫夏草1g/只/d灌服.结果表明,在急性肾毒性损伤早期,尿EGF排泄减少,随着损伤的修复,尿及肾组织中EGF增加,冬虫夏草治疗组大鼠尿及肾组织中EGF升高较庆大组明显,且高峰提前,肾小管修复早,肾功能恢复快.提示冬虫夏草增加EGF的作用可能是它加速肾小管修复、促进肾功恢复的机理之一。     

尿酶测定对肝病患者诊断早期肾功损害的意义

尿酶测定对肝病患者诊断早期肾功损害的意义１１０００３沈阳解放军第２０２医院刘胜利，崔娴维，汤洁，张建新，刘小茹，刘民力尿酶测定是一种监测早期肾功损害的新手段。其中Ｎ－乙酰－β－Ｄ氨基葡萄糖苛酶（ＮＡＧ）和丙氨酸氨基肌酶（ＡＡＰ）是应用最多的尿酶。为测...     

高原性心脏病肾小管功能损害

目的 :探讨高原性心脏病肾小管功能损害情况 ,为保护高原性心脏病肾功能提供实验依据 ;方法 :用酶联免疫法检测 2 2例高原性心脏病患者和 1 0例健康中老年人的尿视黄醇结合蛋白 (RBP)、N -乙酰 -β -D葡萄苷酶 (NAG)水平。同时测定其血尿素氮(BUN)、血肌酐 (Cr) ;结果 :高原性心脏病患者尿RBP、NAG水平较正常对照组显著升高(P <0 .0 1 ) ,而血BUN、Cr无显著差异 (P >0 .0 5 )。其中心功能Ⅲ、Ⅳ级患者较Ⅰ、Ⅱ级患者的RBP、NAG水平有显著差异 (P <0 .0 1 ) ;结论 :高原性心脏病患者存在肾小管功能损害 ,尿RBP、NAG检测是判断其早期肾小管功能损害的敏感指标。动态监测尿RBP、NAG水平变化有助于早期发现其肾小管功能损害情况 ,为指导临床用药、保护高原性心脏病患者肾功能具有一定临床价值     

彩色多普勒超声与临床实验在妊高征监测中的应用

目的探讨彩色多普勒超声检测肾内小动脉血流频谱和放免测定血、尿中β2-微球蛋白在妊高征者中的变化，为妊高征的早期诊断及治疗，评估预后提供敏感可靠的指标。材料与方法99例孕产妇分成正常妊娠组46例、妊高征组53例，分别于产前检测血和尿β-微球蛋白，重度妊高征同时产前彩超监测肾小动脉多普勒血流频谱变化。结果产前重度妊高征彩超肾小动脉S/D为2．38，明显高于正常妊娠组，P＜0．01；血、尿β2-G明显高于正常妊娠组，P＜0．01。结论RIAβ2-MG和彩超检测肾小动脉血流频谱可早期发现妊高征轻度肾脏损害，并估价妊高征预后，对于减少孕产妇围产期并发症具有重要意义。     

尿微量白蛋白与尿酶联合检测对糖尿病肾病的早期诊断价值

目的 探讨尿微量白蛋白(mA)联合尿酶诊断糖尿病早期肾脏损害的价值。方法 对127例糖尿病患者,采用免透射比浊法检测尿mA,速率法检测N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、β-D-半乳糖苷酶(GAL)、甘氨酰脯氨酸二肽氨肽酶(GPDA),Jaffe速率法测尿肌酐。结果 糖尿病患者尿mA,NAG,GAL,GPDA均较对照组显著增高(P<0.01)。单检测mA,NAG,GAL,GPDA阳性率较低,联合四项检测阳性率可达70.1％。尿mA与NAG,GAL,GPDA呈显著正相关。论 联合检测尿mA及尿酶是诊断糖尿病肾脏早期损伤的灵敏、可靠的实验室指标。     

胰激肽原酶联合卡托普利治疗高血压肾病临床观察

高血压病是临床常见病、高发病，肾脏损害是高血压病常见的靶器官损害。肾功能衰竭一旦发生，很难以内科方法予以治疗。所以早期发现肾功能变化并选择合适药物及时干预，对控制蛋白尿和延缓。肾功能衰竭的进程有着重要的临床意义。本文就卡托普利和胰激肽原酶对高血压患者24h尿白蛋白的变化进行临床观察。     

庆大霉素的肾毒性及其所致的急性肾功能衰竭(附3例分析)

报告3例与庆大霉素治疗有关的急性肾功能衰竭,其中2例单纯为庆大霉素肾中毒所致。另1例虽有外伤史,但庆大霉素的肾毒性不容忽视。通过分折上述3例急性肾功能衰竭的发病原因,就临床上如何合理使用庆大霉素等问题进行了讨论。     

Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity.     

尿N-乙酰-β-D氨基葡萄糖酶、丙氨酸氨肽酶和α1-微球蛋白检测在唑来膦酸致肾损伤早期诊断作用

目的探讨尿N-乙酰-β-D氨基葡萄糖酶(NAG)、丙氨酸氨肽酶(AAP)和α1-微球蛋白(α1-MG)检测在唑来膦酸致肾损伤早期诊断中的作用。方法选取2012年2月至2014年7月沈阳军区总医院收治的100例应用唑来膦酸治疗的恶性肿瘤骨转移患者为研究对象。其中,男性48例,女性52例,年龄25~82岁,平均(60±11)岁。患者接受唑来膦酸注射液4 mg静脉滴注,1次/25~35 d,30 min滴完,连续应用3次。每次用药前和用药次日,留取患者清晨尿液及静脉血,检测并比较尿NAG、AAP、α1-MG和血肌酐(Scr)、尿素氮(BUN)水平。结果每次用药前、后比较尿NAG水平,差异均有统计学意义(P<0.05)。第1次用药前后,尿α1-MG水平比较,差异无统计学意义(P>0.05);而第2次和第3次用药前后,尿α1-MG水平比较,差异有统计学意义(P<0.05)。第1次和第3次用药前后,尿AAP水平比较,差异有统计学意义(P<0.05);而第2次用药前后,尿AAP水平比较,差异无统计学意义(P>0.05)。每次用药前后,Scr、BUN水平比较,差异均无统计学意义(P>0.05)。3次用药后,尿NAG、α1-MG水平组间比较,差异均有统计学意义(P<0.05);Scr、BUN水平组间比较,差异均无统计学意义(P>0.05)。结论唑来膦酸致肾损伤患者尿NAG、AAP和α1-MG水平变化早于血肌酐。尿NAG、AAP和α1-MG联合检测可作为肾损伤的早期诊断指标。     

Intravenous injection of ioxilan, iohexol and diatrizoate. Effects on urine profiles in the rat

Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan.     

Nephrotoxicity of contrast media. Comparison of iopamidol and diatrizoate by measurement of urinary enzymes after urography

An ionic (diatrizoate) and a non ionic (iopamidole) radiocontrast medium were compared as to their nephrotoxicity in a cohort of 21 patients with renal disease, 18 of which with normal renal function. The elevation of the urinary excretion of enzymes from renal tubular cells has been considered as a good index for renal tubular damage. We measured two lysosomal enzymes (NAG and beta glucuronidase) and a brush-border enzyme (gamma GT). In all patients we demonstrated an elevation of urinary excretion of the three enzymes already 12 hours after contrast medium administration. However, the elevation was statistically significant only after employment of the ionic contrast medium and concerned gamma GT and beta-glucuronidase; the urinary excretion of NAG did not vary significantly. Urinary enzymes levels returned to basal values 36 hours after intravenous pyelography. In conclusion, iopamidole showed a lower nephrotoxicity with respect to diatrizoate, as demonstrated by the lower levels of urinary enzymes excretion reached after its use.     

Effects on urine profiles of diatrizoate in hydrated and dehydrated rats. A double cross-over study

Effects of intravenous diatrizoate on urine profiles in hydrated and dehydrated rats were compared. In 12 normal rats albumin, glucose, sodium, and the enzymes LDH and GGT were followed twice over 3 hours. The 6 rats being dehydrated at the first examination were hydrated 28 days later and vice versa. At both examinations diatrizoate affected all profile components significantly during the first two hours and caused a 3 per cent weight loss in both groups. Only one significant difference between the hydrated and dehydrated rats was found: The excretion of the brush border enzyme GGT was 1.5 times higher in the dehydrated than in the hydrated rats in both series. Thus, the effect of diatrizoate on the tubular brush border seems to depend on the state of hydration in normal rats.     

Pretreatment with steroids before intravenous injection of diatrizoate or iohexol. Effects on urine and serum profiles.

The effects on urine and serum profiles of intravenous injection of diatrizoate, iohexol, or saline were studied in male rats pretreated with steroids or saline. Using urinary albumin, glucose, sodium, and the enzymes lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) as markers of glomerular and tubular function, it was found that diatrizoate caused temporary glomerular and tubular dysfunction; the effect was independent of the kind of pretreatment. Iohexol did not cause increased glomerular permeability in steroid- and saline-pretreated rats. When used following saline, iohexol induced increased excretion of three tubular components, whereas iohexol plus steroids caused increased excretion of all five tubular components. The dysfunctional effect of iohexol plus steroids was less than that of diatrizoate plus steroids. The serum components revealed no abnormalities induced by either contrast media or methylprednisolone. Pretreatment with steroids has no effect on the glomerular or tubular dysfunctional effect of diatrizoate, whereas it worsens the temporary tubular dysfunctional effect of iohexol in rats.     

Nephropathy induced by intramuscularly administered glycerol and contrast media in rats. A comparison between diatrizoate, iohexol and ioxilan

Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy.     

Early effect of gadopentetate and iodinated contrast media on rabbit kidneys.

RATIONALE AND OBJECTIVES. The authors compared the physiologic and nephrotoxic effects of the magnetic resonance imaging contrast medium gadopentetate with two conventional radiographic contrast media. METHODS. Rabbits were injected intravenously with one of the following solutions: 1) gadopentetate (0.1 M); 2) iohexol (300 mg I/mL); 3) metrizoate (300 mg I/mL); and 4) NaCl (0.9%). Blood samples were taken before and 5, 15, 45, 90, and 180 minutes after injection of the solutions and were analyzed for creatinine, aldosterone, and contrast media levels. Urine was sampled before and 1, 2.5, and 5 hours after injection of the solutions, and creatinine, leucine amino peptidase (LAP), alkaline phosphatase (ALP), gamma glutaryl transferase (GGT), and N-acetyl beta-D-glucosaminidase (NAG) activities were quantified. RESULTS. Contrast media clearance was similar for gadopentetate, iohexol, and metrizoate. Plasma aldosterone was significantly higher in the two groups injected with iodinated contrast agents compared with the gadopentetate and saline groups in the 3-hour samples. During the 5 hours after injection, the excretion of brushborder enzymes LAP, ALP, and gamma GT was significantly higher for all contrast media compared with pre-contrast values and 0.9% NaCl controls. NAG, a lysosomal enzyme from tubular cells, showed a significant increase compared with pre-contrast values for all contrast media. CONCLUSIONS. Intravenous injection of gadopentetate in rabbits showed nephrotoxicity of the same order as that of conventional iodinated contrast media.     

高原地区原发性肾病综合征肾小管功能损害及预后的关系

目的 :探讨高原地区 (海拔 3 680m)原发性肾病综合征 (PNS)肾小管功能损害及与泼尼松疗效的关系 ;方法 :PNS患者经泼尼松 1mg (kg·d)正规治疗 8周后根据疗效分为有效组 (n =3 8)和无效组 (n =1 2 ) ,与泼尼松治疗前后对 50例高原地区PNS患者酶联免疫法测定尿视黄醇结合蛋白 (RBP)及N -乙酰 -β-D氨基葡萄糖苷酶 (NAG)、冰点法测定次晨尿渗透压、磺基水杨酸比浊法测定 2 4小时尿蛋白量、碱性苦味酸法测定血清肌酐 ;结果 :①高原地区PNS患者泼尼松治疗前尿RBP( 0 .54± 1 .1 9)mg L、NAG( 1 1 2 .84± 42 .82 )u L及次晨尿渗透压 ( 553 .62± 2 48.91 )mosm L ,与正常对照组间有显著差异 (P <0 .0 1 ) ;②有效组与无效组相比 ,泼尼松治疗前尿RBP( 0 .3 3± 0 .1 6或 0 .68± 0 .1 4 )mg L、NAG( 97.46± 3 2 .53或 1 58.65± 1 2 .98)u L及次晨尿渗透压 ( 61 9.45± 48.92或 3 3 7.81± 2 6.56)mosm L差别有显著性 (P <0 .0 1 ) ,而 2 4小时尿蛋白定量、血清肌酐差别无显著性 (P >0 .0 5) ;③有效组治疗后尿RBP、NAG及渗透压恢复正常 ,而无效组无明显变化 ;结论 :高原地区PNS存在肾小管功能损害 ,其泼尼松疗效可能与肾小管功能损害程度有关     

Effects of intravenous injection of diatrizoate, iohexol or ioxilan on renal size, urine profiles and blood profiles in the rabbit

Diatrizoate, iohexol or ioxilan were injected intravenously in 18 rabbits. The contrast medium passage through the kidneys was recorded on digital subtraction images for the first 50 s followed by 100 mm exposures up to 15 min after injection. The renal area was measured planimetrically. Urine profiles (glucose, phosphate, LDH, GGT, NAG), blood profiles (potassium, urea) and the relative clearance of albumin and sodium were followed for 5 days and compared with a control group injected with saline. All kidneys were examined by light and immunofluorescence microscopy. All three contrast media produced excellent arteriograms and urograms. The three different contrast media caused a rapid increase of the kidney area within the first minute, reaching an average maximum of 10 to 12 per cent after 5 min, followed by a gradual decline. Contrary to expectations the increase in renal area was similar for all three contrast media, so hyperosmolality is no likely explanation of this phenomenon. None of the contrast agents caused significant changes in any of the profile components with one exception: the GGT excretion was significantly elevated during the first 24 h after diatrizoate administration as compared with the effect of saline. Light and immunofluorescence microscopy revealed no differences.