Early dialysis initiation slightly improves survival in advanced CKD

Very early initiation of dialysis results in a modest reduction in mortality and cardiovascular events, but for most patients with advanced chronic kidney disease (CKD), this benefit may not outweigh the burden of a much longer period spent on dialysis, according to a study.

“Our findings provide novel evidence on the optimal timing of dialysis initiation and show that even with maximum estimated glomerular filtration rate (eGFR) separations, the range of plausible effects is likely to be small,” the researchers said. “The modest increase in observed survival for initiation at higher eGFR comes at the expense of earlier dialysis initiation.”

The National Swedish Renal Registry of patients referred to nephrologists was used in this observational cohort study. The researchers included patients with a baseline eGFR between 10 and 20 mL/min/1.73 m² between 1 January 2007 and 31 December 2016 and followed until 1 June 2017. They emulated the design criteria of a clinical trial by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias.

Moreover, the researchers used a dynamic marginal structural model to estimate adjusted hazard ratios (HRs) and absolute risks for 5-year all-cause mortality and major adverse cardiovascular events (MACE) 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 (eGFR_6-7) was used as reference.

A total of 10,290 incident patients with advanced CKD (median age 73 years, 36 percent women, median eGFR 16.8 mL/min/1.73 m²) were included, of whom 3,822 started dialysis, 4,160 died, and 2,446 had a MACE. [BMJ 2021;375:e066306]

A parabolic association was noted for mortality, with the lowest risk for eGFR_15-16. Dialysis initiation at eGFR_15-16 correlated with a 5.1-percent (95 percent confidence interval [CI], 2.5–6.9) lower absolute 5-year mortality risk and 2.9-percent (95 percent CI, 0.2–5.5) lower risk of a MACE, corresponding to HRs of 0.89 (95 percent CI, 0.87–0.92) and 0.95 (95 percent CI, 0.91–0.98), respectively, compared with initiation at eGFR_6-7.

The 5.1-percent absolute risk difference was equivalent to a mean postponement of death of 1.6 months over 5 years of follow-up, but dialysis would need to be initiated 4 years earlier on average. For many patients, the small survival benefit might not offset the increased time on dialysis.

“Our results further suggest that in the absence of symptoms or strong indications, initiation of dialysis may be postponed until lower eGFR values are reached (intent to defer), without a large increase in mortality or cardiovascular events,” the researchers said. “From a societal perspective, the higher costs associated with earlier dialysis initiation make these strategies even less desirable.” [J Am Soc Nephrol 2021;ASN.2020091254; Nephrol Dial Transplant 2021;36:975-982]

When mimicking the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR_10-14v eGFR_5-7) and the achieved eGFRs in IDEAL (eGFR_7-10v eGFR_5-7), the HRs for all-cause mortality were 0.96 (95 percent CI, 0.94–0.99) and 0.97 (95 percent CI, 0.94–1.00), respectively, which were consistent with the results of the randomized IDEAL trial.

“[O]ur study did not investigate whether other parameters, such as volume overload or symptoms, should be taken into consideration when starting dialysis; this requires further study,” the researchers said. “Neither did our study investigate the effects of dialysis initiation versus comprehensive conservative management in patients with kidney failure.”