Endemic Primary Distal Renal Tubular Acidosis in Thailand

本项目的目的是调查泰国东北部地方性肾远端肾小管酸中毒（EdRTA）的可能原因。本研究采用现场实验和动物模型实验两种方法进行。研究结果如下：1.实地考察：在泰国乌波府乌波拉贾他尼乌波地区医院设立了研究中心。选择EdRTA患者和健康志愿者进行访谈、临床检查和血液和尿液的临床生化分析。还对食物、土壤、水和农产品等材料进行了取样，并将其带到日本进行微量元素分析。结果如下。（1）老年女性多见。他们身高矮小，体重轻。因此，BMI（体重/身高）较低。他们的尿比重下降。（2）EdRTA组尿β_2-微球蛋白含量明显升高，pH值升高。尿肌酐浓度降低。（3）尿钒e ...更多信息 EdRTA组的排泄量显著增加。（4）血浆Mg含量在两性间均较高，K含量均较低。2.低镁饮食动物模型Mg是Na，K-ATP酶和H-ATP酶等ATP酶的必需底物，低Mg有时与低K平行。通常Mg在Henle袢（TAL）的粗升支中被重吸收。因此，我们显微解剖TAL和收集管（CT）从控制和低钾大鼠肾脏的Na，K-ATP酶测定。(1)Na低镁大鼠TAL的K-ATP酶活性明显降低。（2）CT中酶活性显著升高。这一发现是出乎意料的，因为Na，K-ATP酶活性降低应启动血浆K升高，理论上导致dRTA。3.低钾大鼠尿蛋白分析SD大鼠经低钾饮食喂养3个月后，测定其尿蛋白。总蛋白排泄量显著增加。电泳图谱显示，不仅低分子量蛋白质增加，而且高分子量蛋白质也增加。这一结果与临床数据也略有不同。总之，这些结果清楚地表明，电解质和/或微量元素可能在泰国EdRTA的表现中发挥重要作用。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