Department of Nephrology, Medical University of Lublin, Jaczewskiego street 8, 20-954, Lublin, Poland.
Pharmacol Rep. 2022 Feb;74(1):27-39. doi: 10.1007/s43440-021-00329-w. Epub 2021 Oct 6.
Kidney diseases have become one of the most common health care problems. Due to a growing number of advanced aged patients with concomitant disorders the prevalence of these diseases will increase over the coming decades. Despite available laboratory tests, accurate and rapid diagnosis of renal dysfunction has yet to be realized, and prognosis is uncertain. Moreover, data on diagnostic and prognostic markers in kidney diseases are lacking. The kynurenine (KYN) pathway is one of the routes of tryptophan (Trp) degradation, with biologically active substances presenting ambiguous properties. The KYN pathway is known to be highly dependent on immunological system activity. As the kidneys are one of the main organs involved in the formation, degradation and excretion of Trp end products, pathologies involving the kidneys result in KYN pathway activity disturbances. This review aims to summarize changes in the KYN pathway observed in the most common kidney disease, chronic kidney disease (CKD), with a special focus on diabetic kidney disease, acute kidney injury (AKI), glomerulonephritis and kidney graft function monitoring. Additionally, the importance of KYN pathway activity in kidney cancer pathogenesis is discussed, as are available pharmacological agents affecting KYN pathway activity in the kidney. Despite limited clinical data, the KYN pathway appears to be a promising target in the diagnosis and prognosis of kidney diseases. Modulation of KYN pathway activity by pharmacological agents should be considered in the treatment of kidney diseases.
肾脏疾病已成为最常见的医疗保健问题之一。由于越来越多患有合并症的高龄患者，这些疾病在未来几十年的患病率将会增加。尽管有可用的实验室检测，但仍未能实现对肾功能障碍的准确和快速诊断，预后也不确定。此外，肾脏疾病的诊断和预后标志物数据也很缺乏。犬尿氨酸（KYN）途径是色氨酸（Trp）降解的途径之一，其生物活性物质具有模糊的特性。KYN 途径高度依赖于免疫系统的活性。由于肾脏是参与 Trp 终产物形成、降解和排泄的主要器官之一，因此涉及肾脏的病变会导致 KYN 途径活性紊乱。本综述旨在总结最常见的肾脏疾病——慢性肾脏病（CKD）中观察到的 KYN 途径变化，特别关注糖尿病肾病、急性肾损伤（AKI）、肾小球肾炎和肾移植功能监测。此外，还讨论了 KYN 途径活性在肾脏癌发病机制中的重要性，以及影响肾脏中 KYN 途径活性的可用药理学药物。尽管临床数据有限，但 KYN 途径似乎是肾脏疾病诊断和预后的一个有前途的靶点。通过药理学药物调节 KYN 途径活性应在肾脏疾病的治疗中得到考虑。
