长期居住镉污染区人体肾脏及骨骼的研究

报道了１０例长期摄取镉的患者的尸检和临床所见。１０例患者临床表现为蛋白尿、糖尿、骨痛及由于肾小管病而逐渐引起的肾功能衰竭。尸检发现慢性镉中毒血患者的肾近小管上皮细胞萎缩、扁平化及紧管上皮细胞基底膜轻度增厚等。１０例患者均有获得性骨软化症，骨软化症的程度与患者肾小管病变程度相宜，这种骨软化症可能与肾小管的病变有重要关系。     

镉染毒后肾小管上皮细胞内氧自由基代谢与损伤之间关系的研究

本文以离体肾小管上皮细胞为研究对象，观察了镉致肾小管上皮细胞损伤时细胞内氧自由基反应及其与细胞超微结构改变之间的关系。结果表明，镉可诱发离体肾小管上皮细胞脂质过氧化反应增强，脂质过氧化产物明显增加，超氧化物歧化酶及过氧化氢酶活性显著受抑，与此同时肾小管细胞出现一系列超微结构改变；抗氧化剂ＶｉｔＥ可使脂质过氧化作用明显减弱。提示镉臻肾小管上皮细胞损伤与氧自由基对细胞膜结构及功能的损伤有关，氧自由基在     

镉对离体肾小管上皮细胞内钙稳态的影响

以离体肾小管上皮细胞为研究对象，重金属镉为损伤因素，观察了镉致肾小管上皮细胞损伤时细胞内钙稳态的变化及其与肾小管上皮细胞损伤之间的关系。结果表明，用重金属镉处理后，肾小管上皮细胞内胞浆游离钙水平明显升高，且同时伴有一系列超微结构的损害；钙通道阻滞剂异丙嗪表现出明显的阻断、保护作用。本实验提示在重金属镉致肾损伤过程中钙超载机制起着很重要的作用。     

镉对离体肾小管上皮细胞的毒性及机理研究

为了进一步了解镉的肾毒性机理，作者采用放射免疫、细胞化学及生物化学分析的方法，观察了重金属镉对离体肾小管上皮细胞功能及代谢方面的直接作用。结果发现，经镉染毒后，肾小管上皮细胞对α－甲基－Ｄ－葡萄糖苷的摄取量明显减少，同时Ｋ离子外流增加，ｃ－ＡＭＰ含量降低，Ｎａ＋－Ｋ＋－ＡＴＰ酶活性明显受抑，在葡萄糖转运过程中，Ｎａ＋－Ｋ＋－ＡＴＰ酶所维持的电化学梯度对Ｎａ／糖转运起着极为重要的作用，肾小管上皮细胞内能源系统受损可能是镉致肾损伤的发病机理之一。此外，本研究尚检测了一组肾小管标志酶及功能酶（ＡＫＰ、γ－ＧＴ、ＬＤＨ、Ｇ－６－ＰＤ、ＮＡＧ）的变化，发现它们可很好地反应肾小管上皮细胞的损伤程度及代谢状态，具有较好的临床实用价值。     

慢性镉中毒早期诊断方法的探讨

本文采用较为敏感的方法对20例镉接触4—16年工人作了检查。尿低分子蛋白β_2—微球蛋白(β_2m)测定有2例增高;尿蛋白园盘电泳测定,4例异常,尿溶菌酶测定,7例增高;尿钙及尿磷测定,20例皆增高,提示镉对肾小管的损害。X线片1例轻度骨质疏松伴左肾结石。尿总羟脯氨酸测定,可作为骨软化症早期生化指标之一,3例增高。职业史、临床症状、血及尿镉水平是慢性镉中毒早期诊断的重要条件。     

镉对溶菌酶肾脏清除率的影响

利用大鼠镉中毒性肾损害模型，观察了镉对溶菌酶肾脏清除率的影响，结果镉染毒组血，尿溶菌酶均升高，肾小管对溶菌酶的重吸收率明显低于对照组，而溶菌酶的肾脏消除率两组差异则无显著性。认为镉染毒组动物肾小管上皮细胞受损害后，抑制了肾上管上皮细胞对溶菌酶的重吸收和降解功能，从而造成血及尿中菌酶浓度升高，而对不经降解的溶菌酶分子运转过程的影响较小。     

镉对大鼠肾小管上皮细胞E-cadherin影响

目的 探讨镉对体内肾小管上皮细胞E-cadherin依赖的黏附连接是否产生损伤作用。方法将大鼠分2组。实验组皮下注射含Cd 1．4mg／kg CdCl2溶液，每周3次，共4周。对照组在相应时间内皮下注射生理盐水。4周后，收集大鼠24螺样，切取肾皮质。测定尿碱性磷酸酶（LDH）活性、尿蛋白和肌酐含量、肾皮质谷胱甘肽（GSH）和丙二醛（MDA）含量，观察肾脏形态学变化及E-cadherin蛋白表达。结果CA组大鼠尿LDH活性和尿蛋白含量与对照组比较均明显升高。肾皮质GSH含量显著升高，MDA含量变化不明显。Cd组大鼠近端小管上皮细胞排列散乱，刷状缘大面积脱落。有局灶性的空泡变性。与对照组比较，Cd组中E-cadherin在肾小管上皮细胞的基底侧表达明显减少。结论在肾脏处于较低水平的氧化损伤时镉就可干扰体内肾小管上皮细胞E-cadherin依赖的黏附连接。E-cadherin是镉肾毒性的相对较早的靶部位；E-cadherin依赖黏附连接的损伤可能是镉肾毒性的一个重要机制。     

镉对肾小管上皮细胞钙黏蛋白的影响

目的 探讨镉对原代培养的肾小管上皮细胞毒作用的早期环节。方法 采用筛网分离法分离Wistar大鼠肾小管上皮细胞;分别用10、20和50μmol/L的CdCl2溶液培养细胞0、1、2和4h,测定细胞活力、细胞内ALP活性、GSH含量、细胞外液LDH活性及上皮细胞钙黏蛋白（E-cadherin）表达。结果 不同浓度的CdCl2作用培养细胞后,可造成细胞内ALP活性下降,并表现出明显的剂量-反应关系和时间-反应关系;50μmol/L CdCl2作用细胞2h时,细胞外液LDH活性已明显高于对照组;4h时细胞内GSH含量与对照组比较显著下降;而10 μmol/L的CdCl2作用细胞2h,即可使肾小管上皮细胞钙黏蛋白在胞浆表达减少。结论 在肾小管上皮细胞没有发生氧化损伤时,Cd^2＋就可干扰肾小管上皮细胞钙黏蛋白依赖的黏附连接;镉对肾小管上皮细胞钙黏蛋白依赖的黏附连接的损伤可能是镉毒性的最早表现之一。     

镉与痛痛病的关系

日本公众卫生协会经日本环境厅的委托,调查了镉与痛痛病的关系,收集了国内外有关痛痛病和慢性镉中毒的研究成果,总结如下: 在痛痛病的发生和发展上,目前还缺乏否定镉起某种作用的根据,给动物投予镉的实验未复制成定型的骨软化症。对日本镉作业工人的流行病学调查,发现有肾小管的机能性障碍者,而未见有呼吸器和骨障碍者。因此,未能证实镉致肾     

成人紫癜性肾炎肾脏病理评分与临床的关系(附146例报告)

本文探讨成人紫癜性肾炎肾脏病理定量分析与临床表现之间的关系。作者对146例紫癜性肾炎患者的肾小球、肾小管病理改变进行评分及临床分型。结果表明，轻型患者也可有较重的肾小球病变；病程长、蛋白尿是影响肾小管病变程度重要因素，小管间质损伤是影响肾功能的重要指标。     

Reversible tubular dysfunction that mimicked Fanconi's syndrome in a patient with anorexia nervosa.

Patients with anorexia nervosa exhibit acid-base and electrolyte disturbances. Hypophosphatemia is commonly found in these patients during nutritional recovery. However, marked, possibly, life-threatening hypophosphatemia associated with proximal tubular dysfunction has not been previously described. We report a case of anorexia nervosa complicated by a nonacidotic proximal tubulopathy, which was manifested by renal glycosuria, as well as inappropriate phosphaturia and uricosuria resulting in hypophosphatemia and hypouricemia.     

Occupational cadmium exposure in jig solderers.

The cadmium body burden, blood and urine cadmium concentrations, and renal function were studied in a group of 53 cadmium solderers. The results showed raised blood and urine cadmium concentrations and raised cadmium body burden in all workers (31) with more than five years exposure, with 27 having urine cadmium concentrations in excess of the proposed biological threshold of 10 nmol/mmol creatinine. Renal tubular dysfunction was found in 17 of the subjects with more than five years exposure and in one this was associated with glomerular dysfunction. These data indicate that cadmium body burden and frequency of tubular dysfunction in end users of cadmium may be as high as those found in smelters or production workers. Subjects with tubular dysfunction did not show greatly increased urine cadmium concentrations compared with those without dysfunction, supporting a previous suggestion that tubular dysfunction occurs before the wash out of cadmium from the kidney. At the time of our study, cadmium exposure stopped as cadmium free soldering rods were introduced. Repeat urine samples from 19 subjects, one to two years after exposure ended indicated that there was no further increase in the level of excretion of low molecular weight proteins, perhaps indicating that the tubular proteinuria does not increase or more severe renal dysfunction develop without continuous exposure.     

Occupational cadmium exposure in jig solderers

The cadmium body burden, blood and urine cadmium concentrations, and renal function were studied in a group of 53 cadmium solderers. The results showed raised blood and urine cadmium concentrations and raised cadmium body burden in all workers (31) with more than five years exposure, with 27 having urine cadmium concentrations in excess of the proposed biological threshold of 10 nmol/mmol creatinine. Renal tubular dysfunction was found in 17 of the subjects with more than five years exposure and in one this was associated with glomerular dysfunction. These data indicate that cadmium body burden and frequency of tubular dysfunction in end users of cadmium may be as high as those found in smelters or production workers. Subjects with tubular dysfunction did not show greatly increased urine cadmium concentrations compared with those without dysfunction, supporting a previous suggestion that tubular dysfunction occurs before the wash out of cadmium from the kidney. At the time of our study, cadmium exposure stopped as cadmium free soldering rods were introduced. Repeat urine samples from 19 subjects, one to two years after exposure ended indicated that there was no further increase in the level of excretion of low molecular weight proteins, perhaps indicating that the tubular proteinuria does not increase or more severe renal dysfunction develop without continuous exposure.     

Nephropathy in cadmium workers: assessment of risk from airborne occupational exposure to cadmium.

To assess the quantitative relation between exposure to airborne cadmium and various markers of renal tubular and glomerular function, 45 male workers employed at a plant that recovers cadmium from industrial waste and 32 male hospital workers of similar age and geographical location were examined. Cumulative external exposure to airborne cadmium (dose) was estimated from historical air sampling data, adjusted for respirator use. Increasing cadmium dose was associated with multiple renal tubular functional abnormalities, including reduced reabsorption of beta-2-microglobulin (beta-2), retinol binding protein (RBP), calcium, and phosphate. Serum creatinine concentration also increased with cadmium dose, suggesting impaired glomerular function. Mean systolic and diastolic blood pressures were higher in the cadmium workers than in the unexposed (134 v 120 mm Hg and 80 v 73 mm Hg respectively), but only systolic blood pressure was significantly associated with cadmium dose in multivariate analyses. Cadmium dose remained the most important predictor of serum creatinine concentration after controlling for age, blood pressure, body size, and other extraneous factors. Logistic regression to model the probability (prevalence) of various renal abnormalities with increasing dose of cadmium was used. The probability of multiple tubular abnormalities and raised serum creatinine concentration increased sharply at cumulative cadmium exposures exceeding 300 mg/m3 days, corresponding to working for 4.3 years at the current permissible United States exposure limit for cadmium dust.     

Nephropathy in cadmium workers: assessment of risk from airborne occupational exposure to cadmium

To assess the quantitative relation between exposure to airborne cadmium and various markers of renal tubular and glomerular function, 45 male workers employed at a plant that recovers cadmium from industrial waste and 32 male hospital workers of similar age and geographical location were examined. Cumulative external exposure to airborne cadmium (dose) was estimated from historical air sampling data, adjusted for respirator use. Increasing cadmium dose was associated with multiple renal tubular functional abnormalities, including reduced reabsorption of beta-2-microglobulin (beta-2), retinol binding protein (RBP), calcium, and phosphate. Serum creatinine concentration also increased with cadmium dose, suggesting impaired glomerular function. Mean systolic and diastolic blood pressures were higher in the cadmium workers than in the unexposed (134 v 120 mm Hg and 80 v 73 mm Hg respectively), but only systolic blood pressure was significantly associated with cadmium dose in multivariate analyses. Cadmium dose remained the most important predictor of serum creatinine concentration after controlling for age, blood pressure, body size, and other extraneous factors. Logistic regression to model the probability (prevalence) of various renal abnormalities with increasing dose of cadmium was used. The probability of multiple tubular abnormalities and raised serum creatinine concentration increased sharply at cumulative cadmium exposures exceeding 300 mg/m3 days, corresponding to working for 4.3 years at the current permissible United States exposure limit for cadmium dust.     

镉作业观察对象尿镉和肾小管损伤效应标志物6年追踪观察

目的 观察职业性镉作业观察对象尿镉及肾小管损伤效应标志物水平的变化, 比较脱离镉作业6年后镉作业观察对象尿肾小管损伤分子-1(KIM-1)的水平。
方法 选取8例职业性镉作业观察对象, 对2009-2014年度的尿镉、尿β₂-微球蛋白及尿维生素A结合蛋白(即视黄醇结合蛋白)水平进行跟踪观察。2014年用ELISA法检测观察对象及正常对照组尿肾小管损伤分子-1(KIM-1)的水平。
结果 停止镉作业后, 观察组的尿镉平均水平略有下降趋势, 但各年度间差异无统计学意义(P>0.05)。停止镉接触后, 观察组尿β₂-MG水平和尿视黄醇结合蛋白水平一直维持在正常范围。观察组各年度尿β₂-MG水平、尿视黄醇结合蛋白水平差异均无统计学意义(P>0.05)。停止镉接触6年后, 观察组尿KIM-1的水平(1.37 ±0.61) ng/mL, 对照组为(0.62 ±0.35) ng/mL, 两组差异有统计学意义(P < 0.05)。
结论 镉作业观察对象脱离镉接触后, 尿镉水平下降不明显, 传统的肾小管功能损害标志物尿β₂-MG及尿视黄醇结合蛋白水平无明显变化, 但尿KIM-1仍存在异常。
     

Copper and zinc levels in serum and urine of cadmium-exposed people with special reference to renal tubular damage

Urinary copper and zinc concentrations and their serum levels were determined in women environmentally exposed to cadmium, including “itai-itai” disease patients and suspected patients, for evaluating the effect of cadmium exposure on metabolism of such essential metals as copper and zinc in human beings. Copper concentrations in the urine of cadmium-exposed women, especially “itai-itai” patients and suspected patients, were much higher than those of nonexposed women. Zinc concentrations in the urine of cadmium-exposed women, however, were not different from those of nonexposed women. Zinc levels in the serum of the “itai-itai” patients were somewhat lower than those of the nonexposed women. On the other hand, serum copper was almost equal in the cadmium-exposed and the nonexposed women. The correlation coefficient between β₂-microglobulin amounts and copper concentrations in the urine of all women examined was as high as 0.95. It is concluded that exposure to cadmium will cause an increase in the excretion of copper in urine, which is attributable to renal tubular damage due to the cadmium exposure, and that urinary zinc excretion is not increased by cadmium exposure, even in the patients who suffer from severe renal tubular damage.     

Assessment of renal function in workers previously exposed to cadmium

Cadmium induced renal effects were examined in 60 workers (58 men, 2 women) previously exposed to cadmium. Tubular damage in the form of beta 2-microglobulinuria was found in 40%, and urinary albumin and orosomucoid increased significantly with increasing urinary cadmium and increasing relative clearance of beta 2-microglobulin. It is suggested that increased albumin excretion is secondary to the tubular damage. In no case was typical glomerular proteinuria found that could be related to cadmium. Histories of renal stones were more common among the workers with high urinary cadmium concentrations. The glomerular filtration rate was measured in 17 of the workers who had pronounced tubular dysfunction. The average glomerular filtration rate for these men was less than the age adjusted predicted value (mean = 84%). Furthermore, there was a significant (p less than 0.05) correlation (r = -0.47) between tubular reabsorption loss and a decreased glomerular filtration rate.     

Assessment of renal function in workers previously exposed to cadmium.

Cadmium induced renal effects were examined in 60 workers (58 men, 2 women) previously exposed to cadmium. Tubular damage in the form of beta 2-microglobulinuria was found in 40%, and urinary albumin and orosomucoid increased significantly with increasing urinary cadmium and increasing relative clearance of beta 2-microglobulin. It is suggested that increased albumin excretion is secondary to the tubular damage. In no case was typical glomerular proteinuria found that could be related to cadmium. Histories of renal stones were more common among the workers with high urinary cadmium concentrations. The glomerular filtration rate was measured in 17 of the workers who had pronounced tubular dysfunction. The average glomerular filtration rate for these men was less than the age adjusted predicted value (mean = 84%). Furthermore, there was a significant (p less than 0.05) correlation (r = -0.47) between tubular reabsorption loss and a decreased glomerular filtration rate.     

Urinary calcium as a biomarker of renal dysfunction in a general population exposed to cadmium

Urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase have been recommended as sensitive indicators of renal dysfunction induced by cadmium. However, an increase in urinary calcium in early renal damage induced by cadmium has been reported both in humans and in animal experiments. To investigate the feasibility of using urinary calcium as a biomarker of renal dysfunction induced by cadmium, two areas were selected in this study, namely, a polluted area with a 3.71 mg/kg cadmium concentration in rice and a control area with a 0.07 mg/kg cadmium concentration. The total number of participants was 499, made up of 252 in the control group and 247 from the cadmium-polluted area. Urinary cadmium, urinary calcium, and zinc concentrations were measured by atomic absorption spectrometry, and beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in urine were analyzed. The levels of urinary cadmium and urinary calcium in persons from the exposed area were significantly higher (P < 0.05) than those in the control area for both men and women, but there was no significant difference regarding urinary zinc between the two areas. A significant dose-response relationship between the prevalence of hypercalciuria and the excretion of urinary cadmium was observed, and a significantly increased prevalence of calciuria was found when excretion of urinary cadmium exceeded 2 micrograms/g creatinine. The findings were similar to those for excess urinary secretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Because cadmium can affect Ca2+ uptake by tubular cells, with decreased renal Ca2+ reabsorption, calciuria may reflect tubular cell damage caused by cadmium. It was concluded that cadmium exposure can result in increased excretion of urinary calcium in a general population and that there is a significant dose-response relationship. Urinary calcium can therefore be used as a biomarker of renal dysfunction induced by cadmium.