Dataset Information

Dialysis Initiation and All-Cause Mortality Among Incident Adult Patients With Advanced CKD: A Meta-analysis With Bias Analysis.

ABSTRACT:

Rationale & objectives

Due to unmeasured confounding, observational studies have limitations when assessing whether dialysis initiation reduces mortality compared with conservative therapy among adults with advanced chronic kidney disease (CKD). We addressed this issue in this meta-analysis.

Study design

Meta-analysis with bias analysis for unmeasured confounding.

Setting & study population

Adults with stage 4 or 5 CKD who had initiated dialysis or conservative treatment.

Selection criteria for studies

Prospective or retrospective cohort studies comparing survival of dialysis versus conservatively managed patients were searched on MEDLINE and Embase from January 2009 to March 20, 2019.

Data extraction

HRs of all-cause mortality associated with dialysis initiation compared with conservative treatment.

Analytical approach

We pooled HRs using a random-effects model. We estimated the percentage of effect sizes more protective than HRs of 0.80 and severity of unmeasured confounding that could reduce this percentage to only 10%. Subgroup analysis was performed for studies with only older patients (aged ? 65 years).

Results

12 studies were included that involved 16,609 dialysis patients and 3,691 conservatively managed patients. A random-effects model suggested that dialysis initiation was associated with a mean mortality HR of 0.47 (95% CI, 0.34-0.64), in which 92% (95% CI, 50%-100%) of the true effects were more protective than HRs of 0.80. To reduce the percentage of HRs < 0.80 to 10%, unmeasured confounder(s) would need to be associated with both dialysis initiation and mortality by relative risks of 4.05 (95% CI, 2.39-4.15), which is equivalent to shifting each study's estimated HR by 2.31-fold (95% CI, 1.51-2.36). Restricting studies to include only older patients did not modify the results.

Limitations

Limited number of studies and evidence on the absence of publication bias.

Conclusions

Our findings suggest that dialysis initiation considerably reduces mortality among adults with advanced CKD. Future bias-adjusted meta-analyses need to assess outcomes beyond mortality.

SUBMITTER: Fu R

PROVIDER: S-EPMC7873831 | biostudies-literature | 2021 Jan-Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dialysis Initiation and All-Cause Mortality Among Incident Adult Patients With Advanced CKD: A Meta-analysis With Bias Analysis.

Fu Rui R Sekercioglu Nigar N Mathur Maya B MB Couban Rachel R Coyte Peter C PC

Kidney medicine 20201203 1

<h4>Rationale & objectives</h4>Due to unmeasured confounding, observational studies have limitations when assessing whether dialysis initiation reduces mortality compared with conservative therapy among adults with advanced chronic kidney disease (CKD). We addressed this issue in this meta-analysis.<h4>Study design</h4>Meta-analysis with bias analysis for unmeasured confounding.<h4>Setting & study population</h4>Adults with stage 4 or 5 CKD who had initiated dialysis or conservative treatment.<h ...[more]

PMID: 33604540

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Project description:The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis therapy at a higher glomerular filtration rate (GFR) has increased during the past decade. Recent data suggest that higher GFR may be associated with increased mortality.A meta-analysis of cohort studies and trials.Patients with advanced CKD.We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis therapy initiation and mortality.Estimated or calculated GFR at dialysis therapy initiation.Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality.16 cohort studies and 1 randomized controlled trial were identified (n = 1,081,116). By meta-analysis restricted to 15 cohorts (n = 1,079,917), higher GFR at dialysis therapy initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03-1.05; P < 0.001). However, there was significant heterogeneity (I(2) = 97%; P < 0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR, 1.03; 95% CI, 1.02-1.04; P < 0.001; residual I(2) = 97%). The highest mortality risk was observed in hemodialysis cohorts (HR, 1.05; 95% CI, 1.02-1.08; P < 0.001), whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR, 1.04; 95% CI, 0.99-1.08, P = 0.1; residual I(2) = 98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR, 0.80; 95% CI, 0.71-0.91; P = 0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR, 1.04; 95% CI, 1.03-1.05; P < 0.001; residual I(2) = 97%).Paucity of randomized controlled trials, different methods for determining GFR, and substantial heterogeneity.Higher estimated rather than calculated GFR at dialysis therapy initiation is associated with a higher mortality risk in patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study.

Project description:Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias.Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate [eGFR] decreased to <10mL/min/1.73m(2)).Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30mL/min/1.73m(2) measured at least 180 days apart.Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation?10mL/min/1.73m(2)) or later (eGFR < 10mL/min/1.73m(2)) and was time-varying.Death from any cause occurring from the time that eGFR was equal to 20mL/min/1.73m(2) through September 15, 2009.The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n=465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10mL/min/1.73m(2). Many participants (n=426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% CI, 0.65-1.11).Interpolated eGFR, moderate sample size, and likely unmeasured confounders.In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias.

Project description:Some variables including age, comorbidity of diabetes, and so on at dialysis initiation are associated with patient prognosis. Cardiovascular (CV) events are a major cause of death, and adequate models that predict prognosis in dialysis patients are warranted. Therefore, we created models using some variables at dialysis initiation. We used a database of 1,520 consecutive dialysis patients (median age, 70 years; 492 women [32.4%]) from a multicenter prospective cohort study. We established the primary endpoint as a composite of the incidence of first CV events or all-cause death. A multivariable Cox proportional hazard regression model was used to construct a model. We considered a complex and a simple model. We used area under the receiver operating characteristic curve (AUROC) to assess and compare the predictive performances of the prediction models and evaluated the improvement in discrimination using the complex model versus the simple model using net reclassification improvement (NRI). We then assessed integrated discrimination improvement (IDI) to evaluate improvements in average sensitivity and specificity. Of 392 deaths, 152 were CV-related. Totally, 506 CV events occurred during the follow-up period (median 1,285 days). Finally, 692 patients reached the primary endpoint. Baseline data were set at dialysis initiation. AUROC for the primary endpoint was 0.737 (95% confidence interval [CI], 0.712-0.761) in the simple model and 0.765 (95% CI, 0.741-0.788) in the complex model. There were significant intergroup differences in NRI (0.44; 95% CI, 0.34-0.53; p < 0.001) and IDI (0.02; 95% CI, 0.02-0.03; p < 0.001). We prepared a Shiny R application for each model to automatically calculate the predicted occurrence probability (https://statacademy.shinyapps.io/App_inaguma_20190717/). The complex model made more accurate predictions than the simple model. However, the intergroup difference was not significant. Hence, the simple model was more useful than the complex model. The tool was useful in a real-world clinical setting because it required only routinely available variables. Moreover, we emphasized that the tool could predict the incidence of CV events or all-cause mortality for individual patients. In the future, we must confirm its external validity in other prospective cohorts.

Project description:Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.

Project description:Rationale & objectiveDepression is prevalent and highly associated with mortality among patients with chronic kidney disease (CKD). Psychological flexibility can be captured as acceptance in psychology, and its improvement by behavioral therapy is associated with reduced depression in some clinical settings. However, no study has been reported on patients with CKD. This study aimed to examine the association between psychological flexibility and depression in patients with CKD.Study designCohort study.Setting & participantsThis multicenter study of 5 hospitals in Japan included patients with nondialysis stage 3-5 CKD or stage 5D CKD receiving hemodialysis or peritoneal dialysis.PredictorPsychological flexibility measured using the 7-item Acceptance and Action Questionnaire (AAQ-II).OutcomesThe prevalence and incidence of depression after 1 year, which was defined by a score ≥ 16 points on the Center for Epidemiologic Studies Depression (CES-D) questionnaire.Analytical approachGamma regression was used in the examination of correlates of the psychological flexibility value. Modified Poisson regression models were fit for the prevalence and incidence of depression.ResultsThe cross-sectional and longitudinal analyses included 433 and 191 patients, respectively. Lower (ie, worse) psychological flexibility levels were associated with hemodialysis and peritoneal dialysis. Higher (ie, better) psychological flexibility levels were associated with lower prevalence of depression (per 5-point increase; adjusted prevalence ratio, 0.75; 95% CI, 0.70-0.80) and lower incidence of depression (per 5-point increase; adjusted risk ratio, 0.72; 95% CI, 0.61-0.85).LimitationsDepression was assessed using the CES-D questionnaire. Cultural differences may exist in the interpretation of AAQ-II scores.ConclusionsBetter psychological flexibility was associated with lower prevalence and incidence of depression in patients with CKD. Further studies are warranted to determine the possible prevention and treatment of depression by the development of behavioral interventions to improve psychological flexibility.

Project description:Subjective global assessment (SGA) is associated with mortality in end-stage renal disease (ESRD) patients. However, little is known whether improvement or deterioration of nutritional status after dialysis initiation influences the clinical outcome. We aimed to elucidate the association between changes in nutritional status determined by SGA during the first year of dialysis and all-cause mortality in incident ESRD patients. This was a multicenter, prospective cohort study. Incident dialysis patients with available SGA data at both baseline and 12 months after dialysis commencement (n?=?914) were analyzed. Nutritional status was defined as well nourished (WN, SGA A) or malnourished (MN, SGA B or C). The patients were divided into 4 groups according to the change in nutritional status between baseline and 12 months after dialysis commencement: group 1, WN to WN; group 2, MN to WN; group 3, WN to MN; and group 4, MN to MN. Cox proportional hazard analysis was performed to clarify the association between changes in nutritional status and mortality. Being in the MN group at 12 months after dialysis initiation, but not at baseline, was a significant risk factor for mortality. There was a significant difference in the 3-year survival rates among the groups (group 1, 92.2%; group 2, 86.0%; group 3, 78.2%; and group 4, 63.5%; log-rank test, P?<?0.001). Multivariate Cox regression analysis revealed that the mortality risk was significantly higher in group 3 than in group 1 (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.27-6.03, P?=?0.01) whereas the mortality risk was significantly lower in group 2 compared with group 4 (HR 0.35, 95% CI 0.17-0.71, P?<?0.01) even after adjustment for confounding factors. Moreover, mortality risk of group 3 was significantly higher than in group 2 (HR 2.89, 95% CI 1.22-6.81, P?=?0.02); there was no significant difference between groups 1 and 2. The changes in nutritional status assessed by SGA during the first year of dialysis were associated with all-cause mortality in incident ESRD patients.

Dataset Information

Dialysis Initiation and All-Cause Mortality Among Incident Adult Patients With Advanced CKD: A Meta-analysis With Bias Analysis.

Rationale & objectives

Study design

Setting & study population

Selection criteria for studies

Data extraction

Analytical approach

Results

Limitations

Conclusions

Publications

Dialysis Initiation and All-Cause Mortality Among Incident Adult Patients With Advanced CKD: A Meta-analysis With Bias Analysis.

Similar Datasets

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