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胱氨酸肾结石:与其形成和发展相关的新方面

Cystine Renal Calculi: New Aspects Related to Their Formation and Development.

作者信息

Grases Felix, Tomàs Nadal Francisca, Julià Florit Francesca, Costa-Bauza Antonia

机构信息

Laboratory of Renal Lithiasis Research, University Institute of Health Sciences Research (IUNICS-IdISBa), University of Balearic Islands, 07122 Palma de Mallorca, Spain.

出版信息

J Clin Med. 2024 May 11;13(10):2837. doi: 10.3390/jcm13102837.

DOI:10.3390/jcm13102837
PMID:38792383
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11122214/
Abstract

: Crystallization experiments of renal-calculi-forming compounds (calcium oxalate, calcium phosphates, uric acid) are normally performed by monitoring these processes during periods of time similar to the residence of urine inside the kidney. Nevertheless, cystine requires high supersaturation for its crystallization, and most experiments last for longer periods. It must be considered that at high supersaturation, the inhibitors of crystalline development have poor effects. : The induction time of crystallization (t) of cystine in experimental conditions similar to those of the formation of cystine renal calculi and the effect of different cystine-binding thiol agents was determined through turbidimetric measurements. We also studied the macro- and microstructure of 30 cystine kidney stones through stereoscopic microscopy and scanning electron microscopy. : Under the studied conditions, the t in absence of crystallization inhibitors was 15 min, and the presence of 9 mM of penicillamine, tiopronin, or N-acetylcysteine totally inhibited crystallization, as their effects relate to the formation of complexes with cystine, although N-acetylcysteine also delayed cystine crystalline development and modified cystine crystal morphology. Cystine stones have traditionally been classified as smooth and rough. The study of their structure shows that all of them begin their formation from a few crystals that generate a compact radial structure. Their subsequent growth, depending on the renal cavity where they are located, gives rise to the rough structure in the form of large blocks of cystine crystals or the smooth structure with small crystals. : To prevent the development of cystine renal stones, the formation of small crystals must be avoided by reducing urinary cystine supersaturation, with N-acetylcysteine being the most effective among the studied cystine-binding thiol agents. Also, the removal of cystine crystals through increased water intake and physical activity can be a very important preventive measure.

摘要

肾结石形成化合物(草酸钙、磷酸钙、尿酸)的结晶实验通常是通过在与尿液在肾脏内停留时间相似的时间段内监测这些过程来进行的。然而,胱氨酸结晶需要高过饱和度,并且大多数实验持续时间更长。必须考虑到,在高过饱和度下,晶体生长抑制剂的效果不佳。:通过比浊法测量确定了在与胱氨酸肾结石形成条件相似的实验条件下胱氨酸结晶的诱导时间(t)以及不同胱氨酸结合硫醇试剂的作用。我们还通过立体显微镜和扫描电子显微镜研究了30颗胱氨酸肾结石的宏观和微观结构。:在所研究的条件下,在没有结晶抑制剂的情况下t为15分钟,9 mM青霉胺、硫普罗宁或N - 乙酰半胱氨酸的存在完全抑制了结晶,因为它们的作用与与胱氨酸形成复合物有关,尽管N - 乙酰半胱氨酸也延迟了胱氨酸晶体生长并改变了胱氨酸晶体形态。传统上,胱氨酸结石分为光滑型和粗糙型。对其结构的研究表明,所有结石都从少数晶体开始形成,这些晶体形成紧密的放射状结构。它们随后的生长,取决于它们所在的肾腔,产生了大的胱氨酸晶体块形式的粗糙结构或小晶体形式的光滑结构。:为了防止胱氨酸肾结石的形成,必须通过降低尿液胱氨酸过饱和度来避免小晶体的形成,在研究的胱氨酸结合硫醇试剂中,N - 乙酰半胱氨酸是最有效的。此外,通过增加饮水量和体育活动来清除胱氨酸晶体可能是一项非常重要的预防措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bc7/11122214/aef46f09c8ea/jcm-13-02837-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bc7/11122214/2a41bfa6b76a/jcm-13-02837-g002.jpg
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本文引用的文献

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Development of convenient crystallization inhibition assays for structure-activity relationship studies in the discovery of crystallization inhibitors.开发用于结晶抑制剂发现中构效关系研究的便捷结晶抑制测定法。
Med Chem Res. 2023 Jul;32(7):1391-1399. doi: 10.1007/s00044-023-03061-7. Epub 2023 Apr 22.
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Association of water intake and hydration status with risk of kidney stone formation based on NHANES 2009-2012 cycles.基于 NHANES 2009-2012 周期的水摄入量和水合状态与肾结石形成风险的关联。
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Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France.
与胱氨酸尿症目前使用的医学治疗方法相关的不良事件和治疗目标:来自法国 442 例患者的一系列结果。
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l-Cystine Diamides as l-Cystine Crystallization Inhibitors for Cystinuria.L-胱氨酸二酰胺作为胱氨酸尿症中L-胱氨酸结晶抑制剂
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EAU Guidelines on Diagnosis and Conservative Management of Urolithiasis.EAU 指南:尿石症的诊断和保守治疗管理。
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Efficacy of Mixtures of Magnesium, Citrate and Phytate as Calcium Oxalate Crystallization Inhibitors in Urine.镁、柠檬酸盐和植酸盐混合物作为尿液草酸钙结晶抑制剂的功效。
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