荷兰莱顿大学医学中心Edouard L Fu团队研究了为降低晚期慢性肾病患者死亡和心血管事件的风险，开始透析的最佳时机。相关论文于2021年11月29日发表在《英国医学杂志》上。

为了确定晚期慢性肾病患者开始透析的最佳估计肾小球滤过率（eGFR），研究组进行了一项全国性的观察队列研究。2007年1月1日至2016年12月31日，研究组通过瑞典国家肾脏登记处招募患者，患者的基线eGFR介于10-20 mL/min/1.73 m²之间，随访至2017年6月1日。

通过使用克隆、审查和加权方法来消除恒定时间偏倚、提前期偏倚和幸存者偏倚，模仿临床试验的严格设计标准。动态边缘结构模型用于估计针对15种透析开始策略（即eGFR值在4-19 mL/min/1.73 m²之间，增量为1 mL/min/1.73 m²）的五年全因死亡和重大不良心血管事件（心血管死亡、非致命性心肌梗死或非致命性卒中）的校正危险比和绝对风险。取6-7 ml/min/1.73m²的eGFR（eGFR6-7）作为参考。

在10290例晚期慢性肾病患者中（中位年龄73岁，36%为女性，中位eGFR为16.8 mL/min/1.73 m²），3822例开始透析，4160例死亡，2446例出现严重心血管不良事件。死亡率呈抛物线关系，eGFR15-16的风险最低。

与eGFR6-7开始透析相比，eGFR15-16开始透析可降低5.1%的五年绝对死亡风险，降低2.9%的重大心血管不良事件风险，相应的危险比分别为0.89和0.94。这5.1%的绝对风险差异对应于五年随访期间平均多生存1.6个月。

然而，透析需要提前四年开始。当模拟早期和晚期（理想）开始透析试验（eGFR10-14与eGFR5-7）的预期策略以及理想状态下实现的eGFR（eGFR7-10与eGFR5-7）时，全因死亡的危险比分别为0.96和0.97，这与随机理想试验的结果一致。

研究结果表明，很早就开始透析与死亡率和心血管事件的适度降低有关。对于大多数患者来说，这样的减少可能不会超过长期透析所带来的负担。

附：英文原文

Title: Timing of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study

Author: Edouard L Fu, Marie Evans, Juan-Jesus Carrero, Hein Putter, Catherine M Clase, Fergus J Caskey, Maciej Szymczak, Claudia Torino, Nicholas C Chesnaye, Kitty J Jager, Christoph Wanner, Friedo W Dekker, Merel van Diepen

Issue&Volume: 2021/11/29

Abstract:

Objective To identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.

Design Nationwide observational cohort study.

Setting National Swedish Renal Registry of patients referred to nephrologists.

Participants Patients had a baseline eGFR between 10 and 20 mL/min/1.73 m2 and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.

Main outcome measures The strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m2 in increments of 1 mL/min/1.73 m2. An eGFR between 6 and 7 mL/min/1.73 m2 (eGFR6-7) was taken as the reference.

Results Among 10290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m2), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR15-16. Compared with dialysis initiation at eGFR6-7, initiation at eGFR15-16 was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR10-14v eGFR5-7) and the achieved eGFRs in IDEAL (eGFR7-10v eGFR5-7), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial.

Conclusions Very early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.

DOI: 10.1136/bmj-2021-066306

Source: https://www.bmj.com/content/375/bmj-2021-066306