Division of Nephrology, Department of Internal Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States.
Front Endocrinol (Lausanne). 2023 Oct 4;14:1232790. doi: 10.3389/fendo.2023.1232790. eCollection 2023.
Diabetic kidney disease (DKD) is a serious complication of diabetes that can lead to end-stage kidney disease. Despite its significant impact, most research has concentrated on the glomerulus, with little attention paid to the tubulointerstitial region, which accounts for the majority of the kidney volume. DKD's tubulointerstitial lesions are characterized by inflammation, fibrosis, and loss of kidney function, and recent studies indicate that these lesions may occur earlier than glomerular lesions. Evidence has shown that inflammatory mechanisms in the tubulointerstitium play a critical role in the development and progression of these lesions. Apart from the renin-angiotensin-aldosterone blockade, Sodium-Glucose Linked Transporter-2(SGLT-2) inhibitors and new types of mineralocorticoid receptor antagonists have emerged as effective ways to treat DKD. Moreover, researchers have proposed potential targeted therapies, such as inhibiting pro-inflammatory cytokines and modulating T cells and macrophages, among others. These therapies have demonstrated promising results in preclinical studies and clinical trials, suggesting their potential to treat DKD-induced tubulointerstitial lesions effectively. Understanding the immune-inflammatory mechanisms underlying DKD-induced tubulointerstitial lesions and developing targeted therapies could significantly improve the treatment and management of DKD. This review summarizes the latest advances in this field, highlighting the importance of focusing on tubulointerstitial inflammation mechanisms to improve DKD outcomes.
糖尿病肾病（DKD）是糖尿病的一种严重并发症，可导致终末期肾病。尽管其影响很大，但大多数研究都集中在肾小球上，而对占肾脏大部分体积的肾小管间质区域关注甚少。DKD 的肾小管间质病变的特征是炎症、纤维化和肾功能丧失，最近的研究表明，这些病变可能比肾小球病变更早发生。有证据表明，肾小管间质中的炎症机制在这些病变的发生和进展中起着关键作用。除了肾素-血管紧张素-醛固酮阻断剂外，钠-葡萄糖共转运蛋白 2（SGLT-2）抑制剂和新型盐皮质激素受体拮抗剂已成为治疗 DKD 的有效方法。此外，研究人员提出了潜在的靶向治疗方法，例如抑制促炎细胞因子以及调节 T 细胞和巨噬细胞等。这些疗法在临床前研究和临床试验中显示出了有希望的结果，表明它们有可能有效治疗 DKD 引起的肾小管间质病变。了解 DKD 引起的肾小管间质病变的免疫炎症机制并开发靶向治疗方法可能会显著改善 DKD 的治疗和管理。本综述总结了该领域的最新进展，强调了关注肾小管间质炎症机制以改善 DKD 结局的重要性。
