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

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 m 2 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 m 2 in increments of 1 mL/min/1.73 m 2. An eGFR between 6 and 7 mL/min/1.73 m 2 (eGFR 6-7) was taken as the reference. Results Among 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m 2), 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 eGFR 15-16. Compared with dialysis initiation at eGFR 6-7, initiation at eGFR 15-16 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 (eGFR 10-14 v eGFR 5-7) and the achieved eGFRs in IDEAL (eGFR 7-10 v eGFR 5-7), 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.