Sandepudi Kirtana, Shah Krish V, Melnick Bradley A, Li Rena A, Ho Kelly, O'Connor Madeline J, Galiano Robert D
Division of Plastic and Reconstructive Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Case Western Reserve University, Cleveland, Ohio, USA.
Int Wound J. 2025 Jul;22(7):e70713. doi: 10.1111/iwj.70713.
Renal disease, including chronic kidney disease (CKD) and end-stage renal disease (ESRD), has a profound impact on wound healing. Multiple studies have demonstrated that renal disease leads to an increased risk of diabetic foot ulcers, the formation of unique wounds like calciphylaxis, slower wound healing and a higher risk of amputation. This review details the interrelated mechanisms by which renal disease impacts wound healing. Motor and sensory neuropathies contribute to wound formation via foot deformities and decreased sensation. Neuropathies also decrease neuropeptide release, impairing angiogenesis and inflammatory regulation. Accumulation of uremic toxins in renal disease leads to vessel wall calcification, impairing blood supply and predisposing patients to calciphylaxis. Vitamin and mineral deficiencies lead to impaired clotting, development of a chronic inflammatory state and decreased collagen production. Renal disease and its comorbidities are also associated with immune dysregulation, increasing the risk of wound infections and promoting the persistence of pro-inflammatory macrophages. While hypoxia-inducible factor-1α (HIF-1α) promotes angiogenesis under hypoxic conditions in normal wound healing, oxidative stress and chronic hypoxia in renal disease generate an environment that compromises the activity of HIF-1α. Inadequate erythropoietin response to hypoxia also leads to anaemia, further impairing oxygen delivery to wound sites. Clinically, these factors result in increased 10-year mortality for patients with DFU and CKD compared to those with DFU alone, both with and without amputation. We must utilise our understanding of the pathophysiology of impaired wound healing in renal disease to target preventative measures, optimise treatment and improve overall outcomes.
肾脏疾病，包括慢性肾脏病（CKD）和终末期肾病（ESRD），对伤口愈合有深远影响。多项研究表明，肾脏疾病会导致糖尿病足溃疡风险增加、形成诸如钙化防御等独特伤口、伤口愈合缓慢以及截肢风险更高。本综述详细阐述了肾脏疾病影响伤口愈合的相关机制。运动和感觉神经病变通过足部畸形和感觉减退导致伤口形成。神经病变还会减少神经肽释放，损害血管生成和炎症调节。肾脏疾病中尿毒症毒素的积累会导致血管壁钙化，损害血液供应并使患者易患钙化防御。维生素和矿物质缺乏会导致凝血功能受损、慢性炎症状态的发展以及胶原蛋白生成减少。肾脏疾病及其合并症还与免疫失调有关，增加了伤口感染的风险并促进促炎性巨噬细胞的持续存在。虽然在正常伤口愈合的缺氧条件下，缺氧诱导因子-1α（HIF-1α）促进血管生成，但肾脏疾病中的氧化应激和慢性缺氧会产生损害HIF-1α活性的环境。对缺氧的促红细胞生成素反应不足也会导致贫血，进一步损害伤口部位的氧气输送。临床上，与单纯患有糖尿病足溃疡的患者相比，无论是否进行截肢，这些因素都会导致患有糖尿病足溃疡和慢性肾脏病的患者10年死亡率增加。我们必须利用对肾脏疾病中伤口愈合受损病理生理学的理解来制定预防措施、优化治疗并改善总体结局。
