FC 067WHEN TO INITIATE DIALYSIS TO REDUCE MORTALITY AND CARDIOVASCULAR EVENTS IN ADVANCED CKD: A NATIONWIDE COHORT STUDY
Authors: Fu Edouard , Evans Marie , Carrero Juan Jesus , Putter Hein , Clase Catherine M , Caskey Fergus , Szymczak Maciej , Torino Claudia , Chesnaye Nicholas , Jager Kitty J , Wanner Christoph , Dekker Friedo W , Van Diepen Merel 
Published: May 2021

Abstract

Background and Aims
There is currently no direct evidence to inform a specific glomerular filtration rate (GFR) to initiate maintenance dialysis. Previous studies are limited by the number of kidney function thresholds compared, immortal time or lead time biases, or small sample sizes. The only randomised trial (IDEAL) found no difference between early versus late start, but confidence intervals were wide.

Method
Nationwide observational cohort study using data from the Swedish Renal Registry between January 1, 2007 and December 31, 2016, with follow-up until June 1, 2017. Included individuals were receiving nephrologist care and had an eGFR between 10-20 ml/min/1.73m2. A randomized trial was emulated using the cloning, censoring and weighting method. Our primary analysis compared late (at an eGFR 5-7 ml/min/1.73m2 [eGFR5-7]), intermediate (eGFR7-10) and early (eGFR10-14) dialysis initiation to validate our analytical methods by comparison with IDEAL. Our secondary analysis compared fifteen dialysis initiation strategies with eGFR values ranging between 4 and 19 ml/min/1.73m2 in increments of 1 ml/min/1.73m2. Study outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE; composite of cardiovascular death, non-fatal myocardial infarction and stroke). Adjusted hazard ratios [HR] and cumulative survival proportions were estimated using a dynamic marginal structural model.

Results
Among 10,290 individuals with advanced CKD (median age 73 years; 36% women; median eGFR 16.8 ml/min/1.73m2), 3725 individuals initiated dialysis, 4160 died and 2446 experienced MACE. In trial emulation, the 5-year mortality risk was 53.0% for eGFR5-7, 50.3% for eGFR7-10 and 49.7% for eGFR10-14. Compared with eGFR5-7, the 5-year absolute mortality risk difference was -2.7% (95% CI, -4.6% to -0.7%) for eGFR7-10 and -3.3% (95% CI, -5.2% to -1.3%) for eGFR10-14, with a HR of 0.97 (0.94-0.99) and 0.96 (0.94-0.99), respectively. The 5-year absolute MACE risk differences were -1.1% (95% CI, -3.8% to 2.1%) for eGFR7-10 and -3.6% (95% CI, -6.0% to -1.0%) for eGFR10-14 compared with eGFR5-7, with a HR of 1.00 (0.97-1.04) and 0.96 (0.97-1.00), respectively. When analysing fifteen eGFR thresholds, initiation at eGFR15-16 was associated with the largest reduction in mortality (absolute difference, -5.9% [95% CI, -8.0% to -3.1%]; HR, 0.88 [95% CI, 0.85-0.92]) and MACE (absolute difference, -4.5% [95% CI, -7.6% to -1.4%]; HR, 0.92 [95% CI, 0.89-0.97]), compared with eGFR4-5. This -5.9% absolute risk difference translates to a mean postponement of death of 1.8 months over 5-years of follow-up. However, dialysis would need to be initiated on average 14 months earlier.

Conclusion
Early dialysis initiation was associated with a modest reduction in mortality and cardiovascular events. Such a reduction may not outweigh the burden of longer dialysis treatment duration for the patient.