Endemic Primary Distal Renal Tubular Acidosis in Thailand

本项目的目的是调查泰国东北部地区地方性肾远端小管性酸中毒(EdRTA)的可能原因。进行了两种方式的试验，即实地考察和动物模型试验。取得的成果如下：1.实地考察：研究中心已落户泰国乌博州乌博拉贾坦尼乌博尔地区医院。选择EDRTA患者和健康志愿者进行访谈、临床检查和血、尿临床生化分析。还对饮食、土壤、水和农产品等材料进行了采样，并将其带到日本进行微量元素分析。研究结果如下：(1)老年女性患者居多。他们身高不高，体重也很轻。因此，BMI(体重/身高^2)较低。(2)EdRTA患者尿β2-微球蛋白含量明显升高，pH值较高。尿肌酐浓度下降。(3)尿钒e…EdRTA的排泄量明显增加。(4)男女血浆镁含量高，钾含量低。2.低镁饮食动物模型是Na，K-ATPase和H-ATPase等ATPase的必需底物，低镁有时与低K平行，通常镁在粗大的Henle‘s loop(TAL)升支被重新吸收。因此，我们显微解剖正常大鼠和低K大鼠肾脏的TAL和集合管(CT)进行Na，K-ATPase测定：(1)低镁大鼠TAL中Na，K-ATPase活性显著降低，(2)CT中酶活性显著升高。这一发现是意想不到的，因为Na，K-ATPase活性降低应该会引发血浆K的升高，从理论上导致dRTA。3.低钾大鼠尿蛋白的分析：SD大鼠给予低钾饮食3个月后，进行尿蛋白电泳谱分析。总蛋白排泄量明显增加。电泳谱不仅显示了低分子蛋白质的增加，也显示了高分子蛋白质的增加。这一结果也与临床数据略有不同。综上所述，这些结果清楚地表明电解质和/或微量元素在泰国EdRTA的表现中可能起着重要作用。较少

The purpose of this project was to investigate possible causes of endemic renal distal tubular acidosis(EdRTA)in Northeastern part of Thailand. Two ways of trials were carried out, fieldwork and animal model experiments. Results obtained are as follows.1.Fieldwork : A research center has been settled at the Ubol District Hospital, Ubol Rajathanee, Ubol Prefecture, Thailand. EdRTA patients and healthy volunteers were selected for interview, clinical examinations and clinical biochemical analyses of blood and urine. Materials such as diet, soil, water and agricultural products were also sampled and brought to Japan for analysis of trace elements. Results are as follows.(1)Most patients were old aged females. They were small in height and light in body weight. Thus, BMI (body weight/hight^2)were low. Their urine gravity decreased.(2)Urinary beta2-microglobulin contents in EdRTA were significantly increased, and pH was high. Urinary creatinine concentrations decreased.(3)Urinary vanadium e … More xcretion was significantly increased in EdRTA.(4)Plasma Mg concentrations were high, and K was low in both sexes. Zn concentrations were high in male EdRTA, and Na was low in the female.2.Animal model with low Mg dietMg is an essential substrate especially for ATPases including Na, K-ATPase and H-ATPase, and low Mg sometimes is parallelled with low K. Usually Mg is reabsorbed in the thick ascending limb of Henle's loop(TAL). We, therefore, microdissected TAL and the collecting tubule(CT)from control and low K rat kidneys for Na, K-ATPase assay.(1)Na, K-ATPase activity in TAL from low Mg rats was significantly lowered.(2)The enzyme activity in CT was significantly increased. This finding is unexpected, since lowered Na, K-ATPase activity should initiate plasma K increase, resulting in dRTA theoretically. This discrepancy should be further investigated.3.Analysis of urinary proteins in hypo K rats.SD rats were treated with low K diet for 3 months, and their urinary proteins were electrophoresed. Total protein excretion was significantly increased. Electrophoretic patterns show increment of not only low molecular proteins but also high molecular proteins. This result is also slightly different from clinical data.In conclusion, these results clearly suggest that electrolytes and/or trace elements may play important roles in manifestation of EdRTA in Thailand. Less