如何访问“结石宝宝之家”及加入“结石宝宝邮件组”在去年的那场三聚氰胺风波中，逾29万小儿出现泌尿系统异常，其中6人死亡。动物研究显示，食物中所含的三聚氰胺和三聚氰酸进入体内可形成不溶于水的复合物，是结石形成的基础，但这样的结果是否可直接套用于人类尚不可知。近日，一项小规模临床研究显示，三聚氰胺与人类泌尿系结石相关，然而病理生理机制可能与动物不同。相关论文2009年1月9日在线发表于爱思唯尔期刊《临床化学学报》(Clinica Chimica Acta)。 近日，中国香港和内地学者联手进行了一项小规模研究，共纳入了15例曾摄入三聚氰胺污染奶粉且超声诊断有尿路结石的患儿，以及20名无结石形成症状但尿液中可监测到三聚氰胺的儿童，试图探究人体内三聚氰胺相关结石形成的机制。该研究中所有发病儿童的年龄都不足3岁，疾病严重程度不一，从急性肾衰竭伴肾积水，到有症状或无症状的结石伴或不伴尿沉渣分析结果异常等。 三聚氰胺本身可致结石 研究者发现，肾结石患儿尿三聚氰胺浓度从0.87~2002 μg/mmol肌酐不等，而对照儿童尿三聚氰胺浓度范围在0.08~37 μg/mmol肌酐。进一步分析发现，尿液中三聚氰胺浓度在7.1 μg/mmol肌酐为安全切点，持续超过此浓度者，泌尿系统结石危险升高。 另外，肾结石体积也与尿液三聚氰胺浓度强烈相关。结石直径在10 mm以下的患儿，其尿液中三聚氰胺浓度每升高10 μg/mmol肌酐，结石直径增加1 mm，提示三聚氰胺暴露水平越高，结石越严重。 由此，研究者认为，三聚氰胺本身可致结石。 结石形成的其他危险因素 超过50%的结石患儿存在尿路结石的其他危险因素，如尿中尿酸或磷酸盐含量高、尿pH值低等。其中尿pH是结石组和对照组间唯一具有显著差异的危险因素，前组患儿尿pH值显著降低。 在结石组中，超过30%的患儿尿酸水平升高，而这可能与三聚氰胺诱导的肾小管损害有关，并且尿酸在酸性环境中更易析出，形成射线可穿透的结石(三聚氰胺结石亦可被射线穿透)。 研究者据此推测，可能三聚氰胺只形成了结石的“核”，其他代谢危险因素则帮助形成了最终的结石。 三聚氰酸似与肾结石形成无关 与动物研究结果不同，此项小规模研究未发现尿液三聚氰酸浓度与肾结石形成相关。结石组与对照组患儿的尿三聚氰酸浓度无显著差异。在三聚氰酸与三聚氰胺之间和三聚氰酸与肾结石体积之间都未观察到相关性。最近一项研究报告，三聚氰酸在污染奶粉中的含量仅为三聚氰胺的1%。研究者推测，在人体内，三聚氰酸可能与结石形成的关系不大。 本试验中观察到的结石特征与既往动物研究中所描述的不同(见图)，似从另一侧面提示，人与动物体内结石形成的病理生理机制可能存在差异。今后对结石成分进行检测，将有助于进一步了解结石形成的机制。
图1为食用含三聚氰胺食品后死亡的猫肾脏病理检验结果，显示肾小管被晶体堵塞[Toxicol Sci 2008， 106(1): 258];图2为从食用污染奶粉的患儿体内分离出的三聚氰胺相关晶体(Clinica Chimica Acta 2009年1月9日在线发表)。 三聚氰胺在人和动物体内引起结石的特征不同。超声检查发现，人体内三聚氰胺相关结石直径在2.5~18 mm不等，其体积较小、质地较软、数量较多，整体呈泥沙状，大多位于肾盂。该研究未发现三聚氰酸与人体内结石相关。 在动物(猫、狗和鱼)体内的结石主要由三聚氰胺与三聚氰酸形成的复合物组成，其晶体有典型的球形形状，质地比较坚硬。（生物谷Bioon.com） 生物谷推荐原始出处： Clinica Chimica Acta doi:10.1016/j.cca.2008.12.035 Diagnosis and spectrum of melamine-related renal disease: Plausible mechanism of stone formation in humans Ching-Wan Lama, , , Lawrence Lanb, Xiaoyan Chec, Sidney Tama, Samson Sai-Yin Wongd, Yue Chenc, Jing Jinc, Shao-Hua Taoe, Xiao-Ming Tangf, Kwok-Yung Yuend and Paul Kwong-Hang Tamb, , aDepartment of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China Background An epidemic of urinary stones affecting children after consumption of melamine tainted milk is unfolding. We defined clinicopathological features of the disease for diagnosis, monitoring, and treatment of this group of patients. Methods A clinicopathological study on exposed children with ultrasonographic evidence of urolithiasis was conducted. Melamine and cyanuric acid levels in the urine were determined by mass spectrometry. Results Disease severity varied from acute renal failure with hydronephrosis to symptomatic or asymptomatic stones with or without abnormal urinalysis. All cases were aged < 3 y with > 50% cases having predisposing urinary metabolic risk factors for urolithiasis. Most of the stones were located in the renal pelvis and measured 2.5–18 mm by ultrasonography. We found a strong correlation between renal stone size and urinary melamine concentration. For stones < 10 mm, a 10 mmol/creatinine increase in urinary melamine concentration is associated with approximately 1 mm increase in the size of the stone. The high degree of correlation strongly suggests that melamine is related to stone formation in humans. Using ROC analysis, we propose that patients who have a persistent melamine level above the optimal cut-off value of 7.1 μg melamine/mmol creatinine in urine might have a significant exposure of melamine-tainted products. Unlike melamine, urinary cyanuric acid is not significantly different between cases and controls. Pathophysiological findings from feeding animals with melamine and cyanuric acid may not be directly applicable to humans. Conclusion Both melamine and urine metabolic lithogenic factors are important for the formation of melamine-related stones. Apart from aiding with case screening and confirmation, the urine melamine level might as well be an indicator of residual melamine load in the body and thus is useful for following-up and monitoring of the confirmed cases. As the stones are small and can be passed out spontaneously, follow-up of these patients with urine melamine will be a convenient tool for monitoring the melamine load of the patients. |
