Sorić Hosman Iva, Cvitković Roić Andrea, Vuković Brinar Ivana, Gulin Tonko, Ćorić Marijana, Rogić Dunja, Lončar Vrančić Ana, Lamot Lovro
Department of Pediatrics, Zadar General Hospital, 23000 Zadar, Croatia.
Department of Nephrology and Urology, Clinic for Pediatric Medicine Helena, 10000 Zagreb, Croatia.
Medicina (Kaunas). 2024 Dec 6;60(12):2015. doi: 10.3390/medicina60122015.
Despite being one of the most common infectious diseases, urinary tract infections (UTIs) still represent a challenge for clinicians to diagnose and treat, especially in the era of growing antibiotic resistance among uropathogenic bacteria. Recent studies investigating the pathophysiology of UTIs have discovered the prominent role of antimicrobial peptides in the urinary tract defense system. Cathelicidin is an evolutionary conserved antimicrobial peptide encoded by one single gene in humans. Except for being stored in neutrophil cytoplasmic granules, cathelicidin is produced by uroepithelial cells rapidly upon contact with a uropathogen, even before leukocytes invade the urinary tract. In addition to its bactericidal effect, cathelicidin acts as a chemoattractant for multiple immune cells and a potent inductor of numerous cytokine synthesis. Such a crucial role in the initial pathogenesis of a UTI makes cathelicidin a potential biomarker for an early UTI diagnosis. Indeed, multiple studies over the last two decades have proved the potential clinical utility of cathelicidin as a UTI diagnostic biomarker. Furthermore, since patients after the resolution of a UTI have been found to express a lower urinary cathelicidin level than healthy controls, decreased cathelicidin levels have been suggested as a risk factor for developing UTI recurrence. Therefore, measuring cathelicidin levels in urine might help in distinguishing patients with a higher risk for a recurrent UTI. Interestingly, except in UTIs, cathelicidin has also been evaluated in other urinary tract diseases and proposed as a biomarker for diagnosing severe vesicoureteral reflux (VUR) and for recognizing renal scar development in patients with VUR. Finally, a prominent role in UTI pathogenesis also makes cathelicidin an attractive therapeutic target for treating UTIs and, lately, different therapeutic agents up-regulating cathelicidin expression have been investigated in this matter. Therefore, the present review aims to summarize the current body of knowledge on the diagnostic, prognostic and therapeutic potential of cathelicidin in urinary tract diseases. For this purpose, three databases (Scopus, Medline and Web of Science) were extensively searched to cover all the published articles. This exhaustive review will update clinicians on the contemporary state of knowledge about the potential clinical utility of cathelicidin in urinary tract diseases and hopefully encourage further research, resulting in improvement in the current management of urinary tract diseases.
尽管尿路感染（UTIs）是最常见的传染病之一，但对于临床医生来说，其诊断和治疗仍然是一项挑战，尤其是在尿路致病细菌抗生素耐药性不断增加的时代。最近对尿路感染病理生理学的研究发现了抗菌肽在尿路防御系统中的重要作用。Cathelicidin是一种在人类中由单一基因编码的进化保守抗菌肽。除了储存在中性粒细胞胞质颗粒中外，Cathelicidin在尿路上皮细胞与尿路病原体接触后迅速产生，甚至在白细胞侵入尿路之前。除了其杀菌作用外，Cathelicidin还作为多种免疫细胞的趋化剂和多种细胞因子合成的强效诱导剂。Cathelicidin在尿路感染初始发病机制中的这一关键作用使其成为早期尿路感染诊断的潜在生物标志物。事实上，过去二十年的多项研究证明了Cathelicidin作为尿路感染诊断生物标志物的潜在临床应用价值。此外，由于发现尿路感染治愈后的患者尿中Cathelicidin水平低于健康对照组，因此Cathelicidin水平降低被认为是尿路感染复发的一个危险因素。因此，检测尿中Cathelicidin水平可能有助于区分复发性尿路感染风险较高的患者。有趣的是，除了在尿路感染中，Cathelicidin也在其他尿路疾病中进行了评估，并被提议作为诊断严重膀胱输尿管反流（VUR）和识别VUR患者肾瘢痕发展的生物标志物。最后，Cathelicidin在尿路感染发病机制中的重要作用也使其成为治疗尿路感染的有吸引力的治疗靶点，最近，在这方面已经研究了上调Cathelicidin表达的不同治疗药物。因此，本综述旨在总结目前关于Cathelicidin在尿路疾病中的诊断、预后和治疗潜力的知识体系。为此，广泛检索了三个数据库（Scopus、Medline和Web of Science）以涵盖所有已发表的文章。这一详尽的综述将向临床医生更新关于Cathelicidin在尿路疾病中潜在临床应用价值的当代知识状态，并有望鼓励进一步的研究，从而改善当前尿路疾病的管理。
