Impact of Timing of Initiation of Dialysis on Mortality

S. Beddhu
2003 Journal of the American Society of Nephrology  
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
more » ... tion 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 low serum creatinine levels and creatinine clearances (CrCl) but high MDRD GFR at initiation of dialysis (12). These resulted in a spurious association of malnutrition with higher MDRD GFR at initiation of dialysis. The misclassification of low creatinine producers as early initiators of dialysis by the MDRD formula and vice versa in high creatinine producers might lead to erroneous interpretation of the effect of timing of dialysis on mortality. In this study, we adopted the propensity score approach to examine the associations of levels of estimated MDRD GFR and measured CrCl at the initiation of dialysis with subsequent mortality in the Dialysis Morbidity Mortality Study Wave II (DMMS II). The USRDS DMMS II is a prospective registry of a national, random sample of incident chronic hemodialysis and peritoneal dialysis patients who initiated dialysis therapy in 1996 and early 1997 in the United States (13-15). Patients with previous renal replacement therapy, duplicate entries, missing USRDS identification numbers, or missing follow-up data and patients younger than 18 yr were ex-
doi:10.1097/01.asn.0000080184.67406.11 pmid:12937307 fatcat:bgr7zpj2vzaijcblbvr73sfahe