Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.

肾脏疾病是导致 COVID-19 和许多其他严重感染预后不佳的已知风险因素。相反，感染是肾病患者第二大最常见的死亡原因。然而，人们对与肾脏疾病 (SIDKD) 相关的潜在继发性免疫缺陷知之甚少。与引发无数流行病学、临床和实验研究活动或干预试验的与肾脏疾病相关的心血管疾病相比，在追踪、理解和治疗靶向 SIDKD 方面的投资很少。为了呼吁更多人意识到 SIDKD 是一种迫在眉睫的未满足的医疗需求，需要各级开展严格的研究活动，我们回顾了 SIDKD 的流行病学和肾脏疾病患者异常免疫表型的许多方面。我们提出了 SIDKD 的定义，并讨论了迄今为止已知的 SIDKD 的致病机制，包括最近对 FGF23 水平升高和高尿酸血症的意外免疫调节作用以及肾脏疾病中肠道菌群分泌组变化的最新见解。作为最终目标，我们的目标应该是开发能够通过使宿主对病原体的防御和对疫苗的免疫反应正常化来降低肾病患者因感染引起的死亡率的疗法。