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

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 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.

First-year mortality in incident dialysis patients: results of the Peridialysis study

“…It has been suggested that this is due to patients with high comorbidity starting dialysis at a higher eGFR [ 42 ] or that eGFR is artificially raised in cachectic patients with a low muscle mass [ 43 ]. Altogether these observations are in accordance with the IDEAL study [ 44 ], a randomized controlled trial which found no difference between early and late DI while in a study in Swedish dialysis patients very early initiation of dialysis was reported to be associated with a modest reduction in mortality and cardiovascular events in Swedish dialysis patients [ 45 ]. Our study thus suggests that DI should primarily be based on clinical rather than biochemical indications, with particular attention paid to patients with a rapid loss of renal function, which may lead to suboptimal DI [ 26 ].…”

Optimal initiation of dialysis in end stage kidney disease patients: is it a resolved question? A Systematic Literature Review

“…Our present systematic review included 13 studies of the last ve years which investigated optimal dialysis initiation in ESKD patients, 9 of the 13 studies mainly focused on the optimal GFR of maintenance dialysis initiation; 7 studies used eGFR [9,11,13,14,16,18,20], 1 study used mGFR [8], 1 study used both [10]. Compared to previous studies, wider range of GFR values and more detailed data strati cation were applied in the study design and data processing stages; 7 studies[8, 10,13,14,16,20] taken GFR ≤ 5 mL/min/1.73 m2 or even lower into account, the lowest data range was mGFR < 4.3 mL/min/1.73m2 [10] and the highest range was eGFR 15-16 mL/min/1.73 m2 [13]. 5 studies [9,10,11,14,16] showed none association between GFR and mortality or other adverse outcomes, 2 studies [18,20] showed dialysis initiation at higher GFR levels were with poor prognosis, and 2 studies [8, 13] showed higher GFR levels with better prognosis.…”

“…The study about urgent vs. early-start peritoneal dialysis by Silva et al [15] was the one study that did not use Cox regression and used rst 30-day complications, 6-month hospitalization events and 6-month dropout as outcomes. The nationwide cohort study from Sweden was the one study which estimated the effect of each dialysis initiation strategy on ve year all-cause mortality and major adverse cardiovascular events by using a weighted pooled logistic regression model [13]. Based on quality assessment scores, the Newcastle-Ottawa score of these 13 studies was 6 to 7.…”

The safety and feasibility of incremental dialysis must be proven before its widespread use

“…In an observational cohort study, very early initiation of dialysis at an estimated glomerular filtration rate of 15-16 ml/min per 1.73 m 2 was associated with a modest reduction in mortality and cardiovascular events as compared with dialysis initiation at an estimated glomerular filtration rate of 6-7 ml/min per 1.73 m 2 . 6 This reduction corresponded to a mean delay of death of 1.6 months over 5 years of follow-up, but dialysis would need to be started 4 years earlier.…”