Ebata K, Kikkawa R, Haneda M, Shigeta Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Nihon Jinzo Gakkai Shi. 1992 Aug;34(8):901-8.
Glomerular filtration rate has been found to be elevated in the early stage of insulin-dependent diabetes mellitus and has been proposed to play a pathogenetic role in the development of diabetic nephropathy. However, the reports about the change in renal plasma flow (RPF) among diabetic subjects were inconsistent, suggesting that the presence of hyperglycemia may in some way interfere the procedures of RPF measurement. Recently, it has been reported that the glucose in the urine may react with p-aminohippurate (PAH), a widely used marker for RPF measurement, and influence the chemical measurement of PAH, misleading the result of RPF value. In fact, we obtained the decrease of PAH value in urine samples obtained from diabetic subjects during the storage for one week in frozen condition. In order to clarify the factors which may influence the glucose-PAH reaction, we have conducted various in vitro studies. The decrease of PAH values was dose-dependent to urine glucose. The pH of the test solution or urine was also found to greatly influence the result of PAH measurement when glucose was present. The analysis of glucose-PAH reactants by HPLC suggested that the amino residue of PAH might be reacted with glucose, producing the glycation product (Schiff base). The rate of glycation of PAH was time- and pH-dependent. However, when the reaction time was prolonged at the last step of PAH measurement after the addition of the acid solution, the decrease of PAH value was gradually corrected reaching to the theoretical value in 7 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
在胰岛素依赖型糖尿病早期,肾小球滤过率已被发现升高,并且有人提出它在糖尿病肾病的发展中起致病作用。然而,关于糖尿病患者肾血浆流量(RPF)变化的报道并不一致,这表明高血糖的存在可能在某种程度上干扰RPF的测量过程。最近,有报道称尿液中的葡萄糖可能与对氨基马尿酸(PAH,一种广泛用于测量RPF的标志物)发生反应,并影响PAH的化学测量,从而误导RPF值的结果。事实上,我们发现从糖尿病患者获取的尿液样本在冷冻条件下储存一周后,PAH值会降低。为了阐明可能影响葡萄糖 - PAH反应的因素,我们进行了各种体外研究。PAH值的降低与尿糖呈剂量依赖性。当存在葡萄糖时,测试溶液或尿液的pH值也被发现对PAH测量结果有很大影响。通过高效液相色谱法对葡萄糖 - PAH反应物的分析表明,PAH的氨基残基可能与葡萄糖发生反应,产生糖基化产物(席夫碱)。PAH的糖基化速率与时间和pH值有关。然而,在加入酸溶液后PAH测量的最后一步延长反应时间时,PAH值的降低会逐渐得到纠正,在7小时内达到理论值。(摘要截选至250字)