Dataset Information

Cause of Death in Patients With Diabetic CKD Enrolled in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

ABSTRACT:

Background

The cause of death in patients with chronic kidney disease (CKD) varies with CKD severity, but variation has not been quantified.

Study design

Retrospective analysis of prospective randomized clinical trial.

Setting & participants

We analyzed 4,038 individuals with anemia and diabetic CKD from TREAT, a randomized trial comparing darbepoetin alfa and placebo.

Predictors

Baseline estimated glomerular filtration rate (eGFR) and protein-creatinine ratio (PCR).

Outcomes

Cause of death as adjudicated by a blinded committee.

Results

Median eGFR and PCR ranged from 20.6 mL/min/1.73 m(2) and 4.1 g/g in quartile 1 (Q1) to 47.0 mL/min/1.73 m(2) and 0.1 g/g in Q4 (P<0.01). Of 806 deaths, 441, 298, and 67 were due to cardiovascular (CV), non-CV, and unknown causes, respectively. Cumulative CV mortality at 3 years was higher with lower eGFR (Q1, 15.5%; Q2, 11.1%; Q3, 11.2%; Q4, 10.3%; P<0.001) or higher PCR (Q1, 15.2%; Q2, 12.3%; Q3, 11.7%; Q4, 9.0%; P<0.001). Similarly, non-CV mortality was higher with lower eGFR (Q1, 12.7%; Q2, 8.4%; Q3, 6.7%; Q4, 6.1%; P<0.001) or higher PCR (Q1, 10.3%; Q2, 7.9%; Q3, 9.4%; Q4, 6.4%; P=0.01). Sudden death was 1.7-fold higher with lower eGFR (P=0.04) and 2.1-fold higher with higher PCR (P<0.001). Infection-related mortality was 3.3-fold higher in the lowest eGFR quartile (P<0.001) and 2.8-fold higher in the highest PCR quartile (P<0.02). The overall proportion of CV and non-CV deaths was not significantly different across eGFR or PCR quartiles.

Limitations

Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia. Measured GFR was not available.

Conclusions

In diabetic CKD, both lower baseline GFR and higher PCR are associated with higher CV and non-CV mortality rates, particularly from sudden death and infection. Efforts to improve outcomes should focus on CV disease and early diagnosis and treatment of infection.

SUBMITTER: Charytan DM

PROVIDER: S-EPMC4549188 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cause of Death in Patients With Diabetic CKD Enrolled in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

Charytan David M DM Lewis Eldrin F EF Desai Akshay S AS Weinrauch Larry A LA Ivanovich Peter P Toto Robert D RD Claggett Brian B Liu Jiankang J Hartley L Howard LH Finn Peter P Singh Ajay K AK Levey Andrew S AS Pfeffer Marc A MA McMurray John J V JJ Solomon Scott D SD

American journal of kidney diseases : the official journal of the National Kidney Foundation 20150429 3

<h4>Background</h4>The cause of death in patients with chronic kidney disease (CKD) varies with CKD severity, but variation has not been quantified.<h4>Study design</h4>Retrospective analysis of prospective randomized clinical trial.<h4>Setting & participants</h4>We analyzed 4,038 individuals with anemia and diabetic CKD from TREAT, a randomized trial comparing darbepoetin alfa and placebo.<h4>Predictors</h4>Baseline estimated glomerular filtration rate (eGFR) and protein-creatinine ratio (PCR). ...[more]

PMID: 25935581

Similar Datasets

Project description:BackgroundIn a landmark study, TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) examined the use of erythropoiesis-stimulating agent (ESA) therapy to treat anemia among patients with chronic kidney disease (CKD) and found no benefit compared to placebo.Study designA retrospective observational design was used to determine the impact of TREAT on clinical practice.Setting & participantsA large US health plan database with more than 1.2 million claims for patients with non-dialysis-dependent CKD stages 3 and 4.FactorESA prescribing 2 years before and after publication of TREAT.OutcomesRate of ESA prescribing for ESA-naive and -prevalent cohorts.Measurements(1) Monthly ESA prescribing in the 2 years before and after publication of TREAT (ordinary least squares regression), (2) adjusted likelihood of prescribing ESA after TREAT (clustered logistic regression), and (3) probability of receiving ESA therapy based on anemia status (χ(2) test).ResultsFor patients with CKD stage 3, the proportion prescribed ESA therapy declined from 17% pre-TREAT to 11% post-TREAT (a 38% decline), and for those with CKD stage 4, from 34% to 27% (a 22% decline). Prescribing of ESA therapy was declining even before TREAT, but the decline accelerated in the post-TREAT period (stage 3: change of slope, -0.08 [P<0.001]; stage 4: change of slope, -0.16 [P<0.001]). ESA prescribing declined after TREAT regardless of anemia status; among patients with hemoglobin levels <10g/dL, only 25% of patients with CKD stage 3 and 33% of patients with stage 4 were prescribed ESAs 2 years after TREAT, a notable 50% decline. After adjusting for all covariates, the probability of prescribing ESAs was 35% lower during the 2-year period after versus before publication of TREAT (OR, 0.65; 95% CI, 0.63-0.67).LimitationsThe cumulative effect of adverse safety concerns in the period before TREAT also influenced physician prescribing of ESA therapy and could not be separated from the influence of TREAT.ConclusionsTREAT appears to be a watershed study that was followed by a marked decline in ESA prescribing for patients with CKD.

Project description:Rationale & objectiveEvidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes.Study designPost hoc analysis of a randomized controlled trial.Setting & participantsParticipants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n=590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).ExposureRandomized treatment assignment (darbepoetin vs placebo).OutcomesAll-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation.Analytical approachProportional hazards regression.ResultsOverall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n=298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3±1.6 and 9.5±1.5g/dL (P<0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7).LimitationsPost hoc analyses of a subgroup of study participants.ConclusionsDespite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.

Project description:Background and objectivesUromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD.Design, setting, participants, & measurementsWe measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication.ResultsThe mean age of participants was 60±12 years, 60% were male. Mean serum uromodulin concentration was 98±60 ng/ml, eGFR was 49±18 ml/min per 1.73 m2, and 78% had eGFR <60 ml/min per 1.73 m2. Participants in lower serum uromodulin quartiles had lower eGFR and higher albuminuria, prevalence of diabetes, hypertension, coronary artery disease, and more frequent history of stroke at baseline. During a follow-up of 4 years, 335 participants died, 417 developed MACE, and 229 developed kidney failure. In multivariable analysis, the highest serum uromodulin quartile was associated with lower hazard for mortality (hazard ratio [HR], 0.57; 95% CI, 0.38 to 0.87), MACE (HR, 0.63; 95% CI, 0.45 to 0.90), and kidney failure (HR, 0.24; 95% CI, 0.10 to 0.55) compared with the lowest quartile.ConclusionsHigher serum uromodulin is independently associated with lower risk for mortality, cardiovascular events, and kidney failure in white patients with CKD.Clinical trial registry name and registration numberDeutsches Register für Klinische Studien (DRKS; German national database of clinical studies), DRKS00003971.

Dataset Information

Cause of Death in Patients With Diabetic CKD Enrolled in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

Background

Study design

Setting & participants

Predictors

Outcomes

Results

Limitations

Conclusions

Publications

Cause of Death in Patients With Diabetic CKD Enrolled in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets