糖耐量低减者的尿酶检测及分析

尿酶自研究发现以来就被认为是肾脏损伤敏感的实验室指标,目前发现的对肾脏损伤有诊断价值的尿酶有十多种,本实验检测了临床上常见的3种尿酶N-乙酰-β—D氨基葡萄糖苷酶（NAG）、β-D半乳糖苷酶（GAL）及碱性磷酸酶（ALP）的活性,来探讨对糖尿病患者早期肾脏损伤的诊断价值。     

尿微量白蛋白联合尿酶测定在诊断急性脑梗死早期肾损伤中的应用

目的探讨尿微量白蛋白（mALB）联合尿酶测定在诊断急性脑梗死早期肾损伤中的应用价值。方法急性脑梗死组101例,合并高血压61例,合并糖尿病18例,两者均合并者12例,无合并症者34例。对照组为52例健康体检者,留空腹晨尿离心后取上清液分别检测其中的mALB、尿N-乙酰-β-D-氨基酸葡萄糖苷酶（NAG）及尿β-半乳糖苷酶（GAL）,同时测定尿肌酐值,对检测数据进行综合分析。结果急性脑梗死组的mALB、NAG、GAL与对照组比较明显升高（P〈0．05或〈0．01）。急性脑梗死有合并症者尿mALB、NAG及GAL水平高于无合并症者,差异有统计学意义（P〈0．01）。结论mALB联合尿酶检测可作为诊断急性脑梗死早期肾脏损伤的灵敏可靠的实验室指标。     

糖尿病患者早期肾损伤的检测结果分析

目的 探讨尿常规检查蛋白阴性的糖尿病患者早期肾损伤的几率和临床意义.方法 尿微量白蛋白采用微柱层洗法;转铁蛋白(TRF)、免疫球蛋白G(IgG)、a1-微球蛋白(a1-MG)测定采用免疫比浊法;N-乙酰-β-D-氨基葡萄糖苷酶(NAG)测定采用比色法.对206例尿常规检查蛋白阴性的糖尿病患者进行了早期肾损伤指标检测.结果 对照组52例,mAlb:(15.8±6.5)mg/L;TRF:(0.97±0.83)mg/L;IgG(3.7±2.2)mg/L;a1-MG(4.60±0.91)mg/L NAG(13.3±7.1)U/L.糖尿病组206例,mAlb:(98.1±45.2)mg/L;TRF:(3.97±3.10)mg/L;IgG:(12.26±9.87)mg/L;a1-MG:(13.2±10.23)mg/L;NAG:(55.2±32.5)U/L,两组间比较有统计学意义P＜0.01.结论 检测尿中的早期损伤项目,可提前发现肾损伤,阳性率占常规检查蛋白阴性患者的50%,检测尿微量蛋白等对临床具有重要意义.     

uNGAL联合尿NAG对危重症患者急性肾损伤病情及预后的评估价值#br#

摘要：目的　探讨尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）联合尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）对危重症患者急性肾损伤（AKI）病情及预后的评估价值。方法　选取危重症合并AKI的患者101例（AKI组）和同期收治的非AKI患者27例（对照组）。比较2组患者入院后24 h内血肌酐、血钾、血白蛋白和阴离子间隙（AG）、uNGAL、尿NAG、尿蛋白、尿微量白蛋白的差异。AKI组患者根据肾功能损伤严重程度分为Stage 1组（40例）,Stage 2组（36例）和Stage 3组（25例）,另根据患者出院时存活情况,分为存活组（63例）和死亡组（38例）。比较不同严重程度及不同生存状态间上述指标的差异。应用Logistic回归分析危重症患者AKI预后的独立影响因素,受试者工作特征（ROC）曲线评价uNGAL联合尿NAG对危重症患者AKI预后的评估价值。结果　（1）与非AKI组相比,AKI组uNGAL、尿NAG、尿蛋白、尿微量白蛋白、血肌酐水平升高,血清白蛋白水平降低（P＜0.01）。亚组分析结果显示,随着病情的加重,AKI组uNGAL、尿NAG和血肌酐水平均出现明显升高（P＜0.05）;同时死亡组uNGAL、尿NAG、尿微量白蛋白、尿蛋白及血肌酐高于存活组,血清白蛋白低于存活组（P＜0.05）。Logistic回归分析显示,uNGAL和尿NAG升高是影响患者预后的独立危险因素,ROC曲线显示uNGAL联合尿NAG预测预后的曲线下面积（0.886）优于uNGAL（0.850）、尿NAG（0.784）。结论　uNGAL联合尿NAG检测有助于对危重症患者急性肾损伤的危险分层和预后评估。     

窒息新生儿肾功能损害尿N-乙酰-β-D-氨基葡萄糖苷酶的变化

目的 探讨窒息新生儿肾功能损害尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)的变化.方法 对53例窒息新生儿与206例正常新生儿生后第1次尿及24小时左右尿NAG及窒息组尿常规、同期血尿素氮(BUN)与肌酐(Cr)检测.结果 窒息组、轻度窒息、重度窒息组尿NAG活性指数异常率比对照组明显升高(P值均＜0.001).轻度窒息组与重度窒息组比较,尿NAG活性异常率第1次结果有显著性差异(P值均＜0.05),而第2次无显著性差异(P值＞0.05).而血BUN及Cr结果,除Cr第2次有显著性差异(P值＜0.05)外,其余均无显著性差异(P值＞0.05).尿常规比较,两组均无显著性差异.结论 测定尿NAG活性是反映窒息新生儿早期肾小管功能改变的敏感性指标.     

新生儿高胆红素血症尿酶NAG、尿蛋白RBP测定及临床意义

新生儿高胆红素血症是新生儿期的常见疾病,其对中枢神经系统的损害已经得到高度的重视,但对肾脏早期损害尚缺乏敏感指标。我院新生儿科通过测定新生儿高胆红素血症患儿尿酶N-乙酰-β-D氨基葡萄糖苷酶(NAG)活性及尿视黄醇结合蛋白(RBP)含量,探讨高胆红素血症对肾功能的早期损害及临床意义,现报告如下。     

L-FABP和NAG在重症急性胰腺炎合并急性肾损伤中的早期诊断价值

探讨肝型脂肪酸结合蛋白（L-FABP）和N-乙酰-β-D氨基葡萄糖酐酶（NAG）在急性重症胰腺炎（SAP）合并急性肾损伤（AKI）患者中的早期诊断价值。收集15例健康体检者作为正常对照,将161例急性胰腺炎（AP）患者分为轻度（MAP）、中度（MSAP）、重度（SAP）3组,其中SAP 组又分为AKI和非AKI亚组。分别采用酶联免疫分析法（ELISA）和终点法测定正常对照组及AP患者发病后4～24 h的尿液L-FABP、NAG水平。SAP组中AKI亚组的L-FABP和NAG水平明显高于非AKI亚组（P＜0.01）。尿L-FABP和NAG可以作为检测SAP合并 AKI的早期生物标记物。     

尿N-乙酰-β-D-氨基酸氟萄糖苷酶在监测大剂量甲氨蝶呤肾脏毒性作用中的意义

目的探讨尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)在监测大剂量甲氨蝶呤(HDMTX)肾脏毒性作用中的意义。方法对15例急性淋巴细胞白血病(ALL)患儿行HDMTX治疗40例次,每次治疗前1天及治疗后连续3天留取新鲜晨尿,用酶法检测NAG,同时测得Cr以校正。治疗前后测定血尿素氮(BUN)、肌酐(Cr)。结果治疗前后血BUN、Cr比较差异无统计学意义(P>0.05)。治疗后1、2、3d尿NAG明显增高,与治疗前比较差异有统计学意义(P<0.05),治疗后7d尿NAG较治疗前差异无统计学意义(P>0.05)。结论HDMTX对肾脏的损伤是可逆的,可用尿NAG准确地监测HDMTX的早期肾脏损害,以便及时采取措施,防止严重不良反应的发生。     

窒息新生儿血清IL-18及尿NAG水平变化及意义

目的探讨窒息缺氧对新生儿血清白细胞介素18(IL-18)与尿N-乙酰-β-D氨基葡萄糖酐酶(NAG)水平的影响。方法对28例窒息新生儿出生后第1天、治疗10天后血清IL-18、尿NAG进行测定。以20名健康新生儿作对照。结果重度窒息新生儿生后第1天血清IL-18为(175.46±41.24)pg/ml,显著高于健康新生儿的(63.29±14.28)pg/ml(P<0.01);轻度窒息组患者血清IL-18为(118.06±25.31)pg/ml,亦显著高于健康新生儿(P<0.05);治疗后两组窒息患者IL-18水平均显著下降(P<0.05)。窒息患者尿NAG与健康新生儿的比较显著升高(P<0.05)。窒自患者IL-18水平与尿NAG水平呈正相关(P<0.05)。结论窒息缺氧可导致新生儿IL-18与尿NAG水平升高;IL-18可能参与了窒息新生儿肾脏损伤的发病过程。     

尿NAG在糖尿病肾病早期诊断中的临床意义

N-乙酰-β-D氨基葡萄糖苷酶（NAG）是人体内广泛存在且较重要的一种溶酶体水解酶,存在于。肾近曲小管上皮细胞,以近曲小管含量最高。当近端肾小管受损伤时,此酶大量分泌到尿液中,测定酶的活性就可以确定肾小管损伤的程度。因此NAG活性的测定对于多种肾脏疾病引起的。肾损害有重要的临床意义,它可作为肾小管损伤的标志酶。     

The protective effects of thiol-containing compounds on mercuric chloride-induced acute inhibition of enzymes from mouse kidney

The inhibitory effect of mercuric chloride on mouse kidney enzymes and the treatment of this inhibition with some thiol-containing compounds, e.g., dithiothreitol (DTT), dimercaptosuccinic acid (DMS) and D-penicillamine (Pen) was examined. To produce a significant inhibition of renal enzymes in vivo, it was necessary to administer 5 mg Hg/kg/day, s.c., once daily for 3 doses, and to sacrifice the animals 1 day after the last injection. With this Hg dose, microsomal Mg²⁺Na⁺K⁺ATPase, mitochondrial Mg²⁺HCO₃^?ATPase and supernatant carbonic anhydrase actitivities decreased to about 30%, 70% and 60% of normal values, respectively. Combined administration of DTT (5–20 mg/kg, i.p.) and DMS (5–20 mg/kg, i.p.) with HgCl₂ restored the enzyme activities to near normal or normal levels in parallel to the administered doses. The effect of Pen was slightly less than that of the above 2 compounds. This may be due to the number of thiol radicals, as Pen is a monothiol and the other 2 compounds are dithiol compounds. Since the toxicity of DMS is very low compared with DTT, DMS may be more suitable for the treatment of mercury poisoning.     

Effect of milk on intestinal fluid accumulation and renal injury following mercuric chloride ingestion in rats

To investigate the effect of milk on intestinal fluid accumulation and renal injury following mercuric chloride (HgCl(2)) ingestion, 10 ml kg(-1) of saline or 10 mg kg(-1) of HgCl(2) dissolved in 10 ml kg(-1) of water or raw milk was administered enterally to rats and the mercury content in biological samples was determined by cold vapour atomic absorption spectrometry. Three hours after administration, the intestinal water content in rats that received HgCl(2) in water (group S2) was significantly higher than in rats that received saline (group S1) (P < 0.01) or HgCl(2) in milk (group S3) (P < 0.01). The amount of mercury detected per gram dry weight of small intestine was higher in group S2 than in group S3 (P < 0.05). Seventy-two hours after administration, both the serum urea nitrogen and creatinine concentrations in rats that received HgCl(2 )in milk (group L3) were significantly higher than in rats that received saline (group L1) (P < 0.05) or HgCl(2) in water (group L2) (P < 0.05). Mercury levels in many of the biological samples in group L3 were higher than in group L2 (P < 0.05). Milk may reduce the intestinal cytotoxicity of mercury but it promotes its absorption, which may lessen intestinal fluid accumulation but worsen renal injury.     

The effect of antiepileptic drugs on the kidney function and structure

Introduction: Long-term use of antiepileptic drugs (AEDs) is associated with number of somatic conditions. Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the kidney.

Areas covered: This review summarized the current knowledge of the effect of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was reported with valproate (VPA) therapy in severely disabled children with epilepsy. Renal tubular acidosis and urolithiasis were reported with acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition properties. Increased levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (U-NAG/UCr), urinary excretion of α1-micrglobulin, β-galactosidase activity; and urinary malondialdehyde to creatinine (MDA/Cr), markers of renal glomerular and tubular injury, were reported with chronic use of some AEDs (VPA, carbamazepine and phenytoin). The mechanism(s) of kidney dysfunction/injury induced by AEDs is unknown. Experimental and clinical studies have shown that VPA induces oxidative stress, mitochondrial deficits, carnitine deficiency and inflammation and fibrosis in renal tissue in mice and in vitro studies.

Expert commentary: It seems reasonable to monitor kidney function during treating patients with epilepsy at high risk of kidney injury (e.g. on combined therapy with more than one AED, severely disabled children, etc).     

The comparative renotoxicology of phenylmercury and mercuric chloride

The acute renotoxicity of HgCl₂ and phenylmercuric acetate (PhHgAc) was compared at two intraperitoneal dose levels: 0.5 and 1.0 mg Hg/kg. There was no difference in the type of proximal tubular damage caused by the two mercurials, but 1.0mg Hg/kg as PhHgAc produced approximately the same degree of damage as 0.5 mg Hg/kg as HgCl₂. At the selected dose levels only HgCl₂, but not PhHgAc increased the urinary excretion of alkaline phosphatase.At 12 and 24 h after PhHgAc the content of mercury was higher in blood and lower in the kidneys and urine than after the administration of equimolar doses of HgCl₂. As the difference in the renal mercury contents of HgCl₂ and PhHgAc treated groups declined with time, difference in renotoxicity seems to relate only to renal mercury taken up within 24 h of administration. It is suggested that the slower renal extraction of mercury — as in regenerating kidneys (Tandon and Magos 1980) — was responsible for the lower degree of renotoxicity in phenylmercury treated rats.     

镉、汞中毒性肾损伤尿中溶菌酶和碱性磷酸酶活性的变化

在镉、汞亚急性中毒性肾损伤的过程中,尿中溶菌酶活性增高比尿蛋白、尿糖和肾小球滤过率的变化更敏感。尿中碱性磷酸酶活性增高,可能不适宜作为镉中毒性肾损伤的早期指标,但对于汞性肾损伤的早期诊断,具有一定的意义。     

Effect of astaxanthin on kidney function impairment and oxidative stress induced by mercuric chloride in rats.

Reactive oxygen species are implicated as mediators of tissue damage in the acute renal failure induced by inorganic mercury. Astaxanthin (ASX), a carotenoid with potent antioxidant properties, exists naturally in various plants, algae, and seafoods. This paper evaluated the ability of ASX to prevent HgCl(2) nephrotoxicity. Rats were injected with HgCl(2) (0 or 5 mg/kg b.w., sc) 6h after ASX had been administered (0, 10, 25, or 50mg/kg, by gavage) and were killed 12h after HgCl(2) exposure. Although ASX prevented the increase of lipid and protein oxidation and attenuated histopathological changes caused by HgCl(2) in kidney, it did not prevent creatinine increase in plasma and delta-aminolevulinic acid dehydratase inhibition induced by HgCl(2). Glutathione peroxidase and catalase activities were enhanced, while superoxide dismutase activity was depressed in HgCl(2)-treated rats when compared to control and these effects were prevented by ASX. Our results indicate that ASX could have a beneficial role against HgCl(2) toxicity by preventing lipid and protein oxidation, changes in the activity of antioxidant enzymes and histopathological changes.     

镉对大鼠肾脏和睾丸毒性的比较

大鼠饮水中给镉12wk后,检测了尿低分子蛋白(LMWP)排出量。尿碱性磷酸酶(ALP)活性,血清睾酮水平,睾丸乳酸脱氢酶同功酶(LDH-X)活性,精子计数和形态,雄鼠生育力,肾,睾丸和附睾组织镉含量,并在光镜和电镜下观察上述组织的病理变化,从生化,形态和功能改变三方面比较了大鼠肾脏和睾丸对镉的敏感性,发现尿LMWP和ALP仅在高剂量组显著增加,而血清睾酮和睾丸LDH-X在中剂量纽和低剂量纽已明显降低,说明镉对睾丸的有害作用可出现在肾脏之前。     

Nephrotoxicity of mercuric chloride, methylmercury and cinnabar-containing Zhu-Sha-An-Shen-Wan in rats

Cinnabar (HgS) is used in traditional medicines, and total Hg content is used for risk assessment of cinnabar-containing traditional medicines such as Zhu-Sha-An-Shen-Wan (ZSASW). Is ZSASW or cinnabar toxicologically similar to common mercurials? Adult Sprague–Dawley rats were gavaged with ZSASW (1.4 g/kg), cinnabar (0.2 g/kg), HgCl₂ (0.02 g/kg), MeHg (0.001 g/kg), or saline daily for 60 days, and toxicity was determined. Animal body-weight gain was decreased by HgCl₂ and MeHg. Blood urea nitrogen (BUN) was increased by MeHg. Histology showed severe kidney injury following MeHg and HgCl₂ treatments, but mild after ZSASW and cinnabar. Renal Hg contents were markedly increased in the HgCl₂ and MeHg groups but were not elevated in the ZSASW and cinnabar groups. The expression of kidney injury molecule-1 was increased 50-fold by MeHg, 4-fold by HgCl₂, but was unaltered by ZSASW and cinnabar; the expression of matrilysin was increased 3-fold by MeHg. In contrast, the expression of N-cadherin was decreased by HgCl₂. Thus, ZSASW and cinnabar are much less nephrotoxic than HgCl₂ and MeHg, indicating that chemical forms of mercury underlie their disposition and toxicity.     

肾损伤分子1对顺铂诱导的大鼠急性肾损伤的预测研究

目的 对肾损伤分子1 (KIM-1)预测顺铂诱导的大鼠急性肾损伤进行研究.方法 以顺铂为工具药,诱导大鼠急性肾损伤模型.采集尿样、肾组织样本,对肾组织样本进行病理切片检查,以确定造模是否成功.用ELISA法测定尿样中KIM-1蛋白含量;RT-PCR法检测大鼠肾脏KIM-1基因表达水平;Western blotting法检测大鼠肾组织中KIM-1的蛋白含量,并通过免疫组化法定性定位分析大鼠肾组织中KIM-1蛋白表达情况,以确定急性肾损伤发生时KIM-1是否可以作为敏感的检测指标.结果 当模型组大鼠肾脏皮髓交界处出现程度不等的肾小管扩张,肾小管上皮细胞变性、坏死脱落,基底膜裸露等病理改变时,ELISA法检测尿KIM-1,RT-PCR法和Western blotting法检测肾组织中的KIM-1表达水平均明显升高,免疫组化显示模型组所有大鼠在肾皮髓交界部位可见大量的染色阳性的肾小管,该染色阳性区域与组织病理学检查中的异常肾小管分布区域基本一致.结论 KIM-1可作为一种敏感的生物标志物对顺铂诱导的大鼠急性肾损伤进行预测.