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C-Reactive Protein and Risk of ESRD: Results From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

ABSTRACT: To better understand a potential association of elevated C-reactive protein (CRP) level with progression of chronic kidney disease (CKD), we examined the relationship of CRP level with the development of end-stage renal disease (ESRD) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).Post hoc analysis of a randomized controlled trial.4,038 patients with type 2 diabetes, CKD, and anemia in TREAT.Baseline serum CRP concentrations.The primary outcome was development of ESRD; secondary outcomes included doubling of serum creatinine level, a composite of ESRD/serum creatinine doubling, and a composite of death or ESRD.We fit unadjusted and adjusted Cox regression models to test the association of baseline CRP level with time to the development of the outcomes of interest.Mean age of participants was 67 years, 43% were men, and 64% were white. Approximately half (48%) the patients had CRP levels > 3.0mg/L; 668 patients developed ESRD, and 1,270 developed the composite outcome of death or ESRD. Compared with patients with baseline CRP levels ? 3.0mg/L, those with moderately/markedly elevated CRP levels (?6.9mg/L; 24% of patients) had a higher adjusted risk for ESRD (HR, 1.32; 95% CI, 1.07-1.63) and the composite outcome of death or ESRD (HR, 1.41; 95% CI, 1.21-1.64). Although nonsignificant, similar trends were noted in competing-risk models.Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia.Elevated baseline CRP levels are common in type 2 diabetic patients with anemia and CKD and are associated with the future development of ESRD and the composite of death or ESRD.

SUBMITTER: Mc Causland FR

PROVIDER: S-EPMC5123931 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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C-Reactive Protein and Risk of ESRD: Results From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

Mc Causland Finnian R FR Claggett Brian B Burdmann Emmanuel A EA Eckardt Kai-Uwe KU Kewalramani Reshma R Levey Andrew S AS McMurray John J V JJ Parfrey Patrick P Remuzzi Giuseppe G Singh Ajay K AK Solomon Scott D SD Toto Robert D RD Pfeffer Marc A MA

American journal of kidney diseases : the official journal of the National Kidney Foundation 20160916 6

<h4>Background</h4>To better understand a potential association of elevated C-reactive protein (CRP) level with progression of chronic kidney disease (CKD), we examined the relationship of CRP level with the development of end-stage renal disease (ESRD) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).<h4>Study design</h4>Post hoc analysis of a randomized controlled trial.<h4>Setting & participants</h4>4,038 patients with type 2 diabetes, CKD, and anemia in TREAT.<h4>Pre ...[more]

PMID: 27646425

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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:In 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.A retrospective observational design was used to determine the impact of TREAT on clinical practice.A large US health plan database with more than 1.2 million claims for patients with non-dialysis-dependent CKD stages 3 and 4.ESA prescribing 2 years before and after publication of TREAT.Rate of ESA prescribing for ESA-naive and -prevalent cohorts.(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 (?(2) test).For 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).The 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.TREAT appears to be a watershed study that was followed by a marked decline in ESA prescribing for patients with CKD.

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Dataset Information

C-Reactive Protein and Risk of ESRD: Results From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

Publications

C-Reactive Protein and Risk of ESRD: Results From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

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