Impact of Timing of Initiation of Dialysis on Mortality

Abstract

Abstract. Previous studies showed that sicker patients were initiated on dialysis at higher GFR as estimated by the Modification of Diet in Renal Disease (MDRD) formula. It was previously shown that patients with low creatinine production were malnourished and had low serum creatinine levels and creatinine clearances (CrCl) but high MDRD GFR at initiation of dialysis. Therefore, a propensity score approach was used to examine the associations of MDRD GFR and measured CrCl at the initiation of dialysis with subsequent mortality. Baseline data and outcomes were obtained from the Dialysis Morbidity Mortality Study Wave II. Propensity scores for early initiation derived by logistic regression were used in Cox models to examine mortality. Each 5-ml/min increase in MDRD GFR at initiation of dialysis in the entire cohort was associated with increased hazard of death in multivariable Cox model (hazard ratio [HR] 1.14; P ϭ 0.002). In the subgroup of patients with reported CrCl, higher MDRD GFR was associated with increased risk of death (for each 5-ml/min increase, HR 1.27; P Ͻ 0.001) but not CrCl (for each 5-ml/min increase, HR 0.98; P ϭ 0.81). These divergent results might reflect erroneous GFR estimation by the MDRD formula. Furthermore, these data do not support earlier initiation of dialysis. Therefore, for patients without clinical indications for initiation of dialysis, the appropriate GFR level for initiation of dialysis is unknown.Early initiation of dialysis might improve nutrition with consequent decrease in hospitalization, mortality, and costs (1-8). However, early initiation of dialysis also exposes the patient to complications of dialysis, unnecessary lifestyle restriction, and potential increased costs. Thus, the optimal timing of initiation of dialysis is unclear.There are two methodologic issues that need to be considered in observational studies of optimal timing of dialysis. First, randomized controlled trials are considered the gold standard in comparison of different interventions, as effective randomization coupled with sufficient sample size would result in equal distribution of baseline factors across treatment groups. There may be significant imbalances in distribution of key parameters across treatment groups in observational studies because certain clinical conditions might be indications for therapy with one intervention (in this case, early initiation of dialysis) than the other. Indeed, previous studies of the United States Renal Data System (USRDS) data showed that sicker patients were initiated on dialysis at higher GFR as estimated by the Modification of Diet in Renal Disease (MDRD) formula (9). The use of propensity stratification based on propensity scores has been shown to reduce or eliminate the imbalances in distribution of baseline covariables across treatment groups in nonrandomized studies (10,11).Second, the MDRD formula has not been validated in patients with advanced renal failure. Our earlier study showed that patients with low creatinine production were malnourished and had ...

Factors Influencing the Decision to Start Renal Replacement Therapy: Results of a Survey Among European Nephrologists

“…4,[17][18][19] Consistent with our finding that only 7% indicated that the planned start was never delayed, a possible explanation for these differences may be that the actual start usually is later than the planned start.…”

Estimated Glomerular Filtration Rate at Re-Initiation of Dialysis and Mortality in Failed Kidney Transplant Recipients

“…The main concern of observational studies including ours is the difference between the clinical characteristics and dialysis indications of the early and late initiation groups. Patients with early dialysis initiation were more likely to be men and diabetic, have severe heart failure or coronary heart disease, are less likely to have glomerulonephritis or polycystic kidney disease and have lower serum albumin level and more comorbidity and in summary, they are sicker patients [5,9,14,17]. In our DAGL patients, we found similar results.…”

“…Despite the weak evidence, early initiation was accepted and it was common practice until recently. More recent studies, including a randomized controlled trial, did not support early initiation of dialysis in CKD patients [5,8,9,12,[15][16][17][18]. The large multicenter trial from Netherland, the Netherlands Cooperative Study on the Adequacy of Dialysis, was the first observational study which casts doubt on the advantages of early dialysis initiation [7].…”

“…This bias was the first potential explanation for previous smaller studies' opposite results. In 2003, Beddhu et al [9] reported that higher eGFR was associated with higher risk of death, but in a subgroup of patients with measured creatinine clearance, there was no association with mortality. Traynor et al [8], on the other hand, reported that higher creatinine clearance at initiation of dialysis was associated with elevated mortality risk.…”

“…Data from the US Renal Data System (USRDS) between 1996 and 2008 showed that the proportion of patients initiating hemodialysis (HD) with an estimated GFR (eGFR) >10 mL/min/ 1.73m 2 increased from 20 to 52% and those with a starting eGFR of ≥15 mL/min/1.73m 2 increased from 4 to 17% [5,6]. Interestingly, most of the recent observational trials and a landmark randomized controlled trial failed to show a survival benefit of early initiation of dialysis in CKD patients [5,[7][8][9][10][11][12][13][14][15][16][17][18].…”