1 型糖尿病肾病的进展和消退

F. Jansson Sigfrids, P. Groop
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摘要

糖尿病肾病的特征是白蛋白尿、高血压、肾功能衰退和心血管疾病风险明显升高。这一系列临床特征导致 1 型糖尿病患者过早死亡。有关 1 型糖尿病相关白蛋白尿的首次流行病学调查可追溯到 20 世纪 80 年代。早期的研究发现,35% 至 45% 的 1 型糖尿病患者会出现蛋白尿,这在很大程度上等同于重度白蛋白尿,而糖尿病病程特异性的发病率模式会出现一个或两个高峰。此外,中度白蛋白尿是糖尿病肾病的第一个可检测到的迹象,但在短时间内几乎不可避免地发展为明显的肾病。自早期报告以来,出现了更多关于最新发病率的研究,但许多研究都存在重大局限性,如研究人群缺乏广泛的普遍性、研究设计容易出现实质性选择偏差以及随访时间有限等。尽管如此,最新的报告估计,在现代,三分之一的 1 型糖尿病患者会出现中度(而非重度)白蛋白尿;然而,随着时间的推移,相当一部分患者(在最初诊断出白蛋白尿后的前十年中高达 40%)会发展到疾病的晚期阶段。白蛋白尿进展的另一个途径是白蛋白尿的消退,这影响到多达 60% 的个体,但值得注意的是,复发到更晚期疾病阶段的比率很高。白蛋白尿的消退是否意味着心血管疾病和过早死亡风险的下降,这是一个有争议的领域,需要在未来进行更详细的研究。另一个不明确但令人担忧的特点是,虽然严重白蛋白尿的发病率自 20 世纪 30 年代以来一直在下降,但这种下降似乎在 20 世纪 80 年代后达到了一个停滞期。这种停滞可能是由于自 20 世纪 80 年代初以来缺乏保护肾脏的药物,因为最近在 2 型糖尿病方面取得的突破并不适用于 1 型糖尿病。因此,在这一患者群体中,新型治疗策略是当务之急。
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Progression and regression of kidney disease in type 1 diabetes
Diabetic kidney disease is distinguished by the presence of albuminuria, hypertension, declining kidney function, and a markedly elevated cardiovascular disease risk. This constellation of clinical features drives the premature mortality associated with type 1 diabetes. The first epidemiological investigations concerning type 1 diabetes-related albuminuria date back to the 1980s. The early studies found that proteinuria – largely equivalent to severe albuminuria – developed in 35 to 45% of individuals with type 1 diabetes, with the diabetes duration-specific incidence rate pattern portraying one or two peaks. Furthermore, moderate albuminuria, the first detectable sign of diabetic kidney disease, was found to nearly inexorably progress to overt kidney disease within a short span of time. Since the early reports, studies presenting more updated incidence rates have appeared, although significant limitations such as study populations that lack broad generalizability, study designs vulnerable to substantive selection bias, and constrained follow-up times have been encountered by many. Nevertheless, the most recent reports estimate that in modern times, moderate – instead of severe – albuminuria develops in one-third of individuals with type 1 diabetes; yet, a considerable part (up to 40% during the first ten years after the initial albuminuria diagnosis) progresses to more advanced stages of the disease over time. An alternative pathway to albuminuria progression is its regression, which affects up to 60% of the individuals, but notably, the relapse rate to a more advanced disease stage is high. Whether albuminuria regression translates into a decline in cardiovascular disease and premature mortality risk is an area of debate, warranting more detailed research in the future. Another unclear but alarming feature is that although the incidence of severe albuminuria has fallen since the 1930s, the decline seems to have reached a plateau after the 1980s. This stagnation may be due to the lack of kidney-protective medicines since the early 1980s, as the recent breakthroughs in type 2 diabetes have not been applicable to type 1 diabetes. Therefore, novel treatment strategies are at high priority within this patient population.
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