The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis

The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis.BackgroundWhile the survival ramifications of dialysis modality selection are still debated, it seems reasonable to postulate that outcome comparisons are not the same for all patients at all times. Trends in available data indicate the relative risk of death with hemodialysis (HD) compared to peritoneal dialysis (PD) varies by time on dialysis and the presence of various risk factors. This study was undertaken to identify key patient characteristics for which the risk of death differs by dialysis modality.MethodsAnalyses utilized incidence data from 398,940 United States Medicare patients initiating dialysis between 1995 and 2000. Proportional hazards regression identified the presence of diabetes, age, and the presence of comorbidity as factors that significantly interact with treatment modality. Stratifying by these factors, proportional and nonproportional hazards models were used to estimate relative risks of death [RR (HD:PD)].ResultsOf the 398,940 patients studied, 11.6% used PD as initial therapy, 45% had diabetes mellitus (DM), 51% were 65 years or older, and 55% had at least one comorbidity. Among the 178,693 (45%) patients with no baseline comorbidity, adjusted mortality rates in nondiabetic (non-DM) patients were significantly higher on HD than on PD [age 18–44: RR (95% CI) = 1.24 (1.07, 1.44); age 45–64: RR = 1.13 (1.02, 1.25); age 65+: RR = 1.13 (1.05, 1.21)]. Among diabetic (DM) patients with no comorbidity, HD was associated with a higher risk of death among younger patients [age 18–44: RR = 1.22(1.05, 1.42)] and a lower risk of death among older patients [age 45–64: RR = 0.92 (0.85, 1.00); age 65+: RR = 0.86 (0.79, 0.93)]. Within the group of 220,247 (55%) patients with baseline comorbidity, adjusted mortality rates were not different between HD and PD among non-DM patients [age 18–44: RR = 1.19 (0.94, 1.50); age 45–64: RR = 1.01 (0.92, 1.11); age 65+: RR = 0.96 (0.91, 1.01)] and younger DM patients [age 18–44: RR = 1.10 (0.92, 1.32)], but were lower with HD among older DM patients with baseline comorbidity [age 45–64: RR = 0.82 (0.77, 0.87); age 65+: RR = 0.80 (0.76, 0.85)].ConclusionValid mortality comparisons between HD and PD require patient stratification according to major risk factors known to interact with treatment modality. Survival differences between HD and PD are not constant, but vary substantially according to the underlying cause of ESRD, age, and level of baseline comorbidity. These results may help identify technical advances that will improve outcomes of patients on dialysis

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

Background: Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects. Methods: To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable metaregression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. Results: The mean acute effect across all studies was 20.21 ml/min per 1.73 m2 (95% confidence interval, 20.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, 22.50 to 12.08 ml/min per 1.73 m2). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR. Conclusion: The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD

Relative Efficiencies in the Multivariate Analysis of Repeated Measurements.

Frequently in the life sciences, the scope of an experimental study is such that the application of several treatments to a single experimental unit will not alter the nature of that unit. When this occurs, the experimenter has a choice between applying some or all of the treatments to a given unit or selecting independent units to receive each treatment combination. The former choice leads to what is commonly referred to as a repeated measures design (RMD) while the latter choice results in a completely crossed r and omized design (CCRD). While much is known regarding the theory and analysis of a RMD, little attention has been given to a priori considerations for choosing a RMD over the corresponding CCRD. This is particularly true with respect to a multivariate analysis of repeated measurements. It is the objective of this research to provide the experimenter with a means for choosing between a RMD and CCRD. The specific goals of this research are to determine conditions under which a RMD, when analyzed multivariately, is more or less efficient than the corresponding CCRD and to formulate a means by which sample sizes for a RMD can be determined. Following the work of Cole and Grizzle (1966) and Timm (1975), a multivariate general linear model is developed for a K-factor RMD in which the factors are grouped into "within unit" and "between unit" factors. A corresponding CCRD general linear model is provided and the two models are formulated so as to better compare the relative efficiency of the two designs. The efficiency of the two designs is compared by means of the ratio of expected squared half lengths of Scheffe'-type confidence intervals. By comparing relative efficiency with respect to pairwise comparisons, an algorithm is presented for determining sample sizes in the multivariate analysis of a single-factor RMD. Numerical and analytical results suggest that a RMD will often be more efficient than its CCRD counterpart for comparisons involving "within unit" treatment combinations. However, for comparisons restricted to "between unit" factors, the RMD will, in almost all cases, be less efficient than the corresponding CCRD.Ph.D.BiostatisticsUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/159854/1/8402399.pd

The outcomes of continuous ambulatory and automated peritoneal dialysis are similar.

Recent reports indicate a decreased mortality risk for patients on chronic peritoneal dialysis in the United States. We sought to determine whether a higher use of automated versus continuous ambulatory peritoneal dialysis was associated with this improvement. Analyses were carried out using data from the United States Renal Data System on 66,381 incident patients on chronic peritoneal dialysis in the years 1996-2004 that were adjusted for demographic, clinical, laboratory and dialysis facility characteristics. Patients were followed until the time of transfer to other modes of dialysis, transplant, or death, whichever occurred first, or until their last follow-up through September 2006. Over time, the risks were substantially reduced such that the adjusted hazard ratios for death or technique failure of these patients in the 2002-2004 period were 0.55 (0.53, 0.57) and 0.62 (0.59, 0.64), respectively, compared with those of incident patients during the years 1996-1998. The risk improvements for both modes of dialysis were, however, found to be similar. Under intent-to-treat, time-dependent, and as-treated analysis, there was little or no difference in risk for death or in technique failure. Thus, the improved chronic peritoneal dialysis outcomes cannot be attributed to a greater use of automated peritoneal dialysis

The outcomes of continuous ambulatory and automated peritoneal dialysis are similar.

Recent reports indicate a decreased mortality risk for patients on chronic peritoneal dialysis in the United States. We sought to determine whether a higher use of automated versus continuous ambulatory peritoneal dialysis was associated with this improvement. Analyses were carried out using data from the United States Renal Data System on 66,381 incident patients on chronic peritoneal dialysis in the years 1996-2004 that were adjusted for demographic, clinical, laboratory and dialysis facility characteristics. Patients were followed until the time of transfer to other modes of dialysis, transplant, or death, whichever occurred first, or until their last follow-up through September 2006. Over time, the risks were substantially reduced such that the adjusted hazard ratios for death or technique failure of these patients in the 2002-2004 period were 0.55 (0.53, 0.57) and 0.62 (0.59, 0.64), respectively, compared with those of incident patients during the years 1996-1998. The risk improvements for both modes of dialysis were, however, found to be similar. Under intent-to-treat, time-dependent, and as-treated analysis, there was little or no difference in risk for death or in technique failure. Thus, the improved chronic peritoneal dialysis outcomes cannot be attributed to a greater use of automated peritoneal dialysis

Similar outcomes with hemodialysis and peritoneal dialysis in patients with end-stage renal disease.

BackgroundThe annual payer costs for patients treated with peritoneal dialysis (PD) are lower than with hemodialysis (HD), but in 2007, only 7% of dialysis patients in the United States were treated with PD. Since 1996, there has been no change in the first-year mortality of HD patients, but both short- and long-term outcomes of PD patients have improved.MethodsData from the US Renal Data System were examined for secular trends in survival among patients treated with HD and PD on day 90 of end-stage renal disease (HD, 620 020 patients; PD, 64 406 patients) in three 3-year cohorts (1996-1998, 1999-2001, and 2002-2004) for up to 5 years of follow-up using a nonproportional hazards marginal structural model with inverse probability of treatment and censoring weighting.ResultsThere was a progressive attenuation in the higher risk for death seen in patients treated with PD in earlier cohorts; for the 2002-2004 cohort, there was no significant difference in the risk of death for HD and PD patients through 5 years of follow-up. The median life expectancy of HD and PD patients was 38.4 and 36.6 months, respectively. Analyses in 8 subgroups based on age (<65 and ≥65 years), diabetic status, and baseline comorbidity (none and ≥1) showed greater improvement in survival among patients treated with PD relative to HD at all follow-up periods.ConclusionIn the most recent cohorts, patients who began treatment with HD or PD have similar outcomes

Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD