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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Copeptin, Natriuretic Peptides, and Cardiovascular Outcomes in Patients With CKD: The German Chronic Kidney Disease
Markus P Schneider1, Matthias Schmid2, Jennifer Nadal2
1Department of Nephrology and Hypertension, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Insights
In patients with chronic kidney disease (CKD), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) strongly predicts adverse outcomes. The novel marker Copeptin also independently predicts non-cardiovascular death and heart failure hospitalizations, suggesting its utility in risk assessment.
Area of Science:
- Biomarker discovery in chronic kidney disease (CKD)
- Cardiovascular risk stratification
- Nephrology and Cardiology
Background:
- Copeptin and Midrange pro-atrial natriuretic peptide (MR-pro-ANP) are known predictors of outcomes in heart failure (HF).
- Their prognostic value in patients with chronic kidney disease (CKD) remains unstudied.
- Identifying reliable biomarkers for cardiovascular risk in CKD is crucial for guiding interventions and improving patient outcomes.
Purpose of the Study:
- To investigate the association of Copeptin, MR-pro-ANP, and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) with major adverse outcomes in patients with moderately severe CKD.
- To determine if Copeptin and MR-pro-ANP offer independent prognostic information beyond NT-pro-BNP in this population.
Main Methods:
- Prospective cohort study involving 4,417 patients from the German Chronic Kidney Disease (GCKD) study.
- Participants had an estimated glomerular filtration rate of 30-60 mL/min/1.73m² or overt proteinuria.
- Baseline measurements of Copeptin, MR-pro-ANP, and NT-pro-BNP were analyzed using Cox regression, adjusting for established risk factors.
Main Results:
- Over a median follow-up of 6.5 years, significant associations were observed between all three biomarkers and non-cardiovascular death, cardiovascular death, major adverse cardiovascular events (MACE), and heart failure hospitalizations.
- NT-pro-BNP showed the strongest associations across all outcomes.
- When all three markers were included in multivariable models, NT-pro-BNP remained significant for all outcomes. Copeptin demonstrated independent associations with non-cardiovascular death and heart failure hospitalizations.
Conclusions:
- NT-pro-BNP is a strong predictor of adverse outcomes in patients with moderately severe CKD.
- The novel biomarker Copeptin independently predicts non-cardiovascular death and hospitalizations for heart failure in this cohort.
- Copeptin warrants further evaluation as a valuable tool for cardiovascular risk assessment in patients with CKD.
Rationale & Objective:
Copeptin and Midrange pro-atrial natriuretic peptide (MR-pro-ANP) are associated with outcomes independently of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in patients with heart failure (HF). The value of these markers in patients with chronic kidney disease (CKD) has not been studied.
Study Design:
Prospective cohort study.
Setting & Participants:
A total of 4,417 patients enrolled in the German Chronic Kidney Disease (GCKD) study with an estimated glomerular filtration rate of 30-60 mL/min/1.73m2 or overt proteinuria (urinary albumin-creatinine ratio >300mg/g or equivalent).
Exposures:
Copeptin, MR-pro-ANP, and NT-pro-BNP levels were measured in baseline samples.
Outcomes:
Noncardiovascular death, cardiovascular (CV) death, major adverse CV event (MACE), and hospitalization for HF.
Analytical Approach:
HRs for associations of Copeptin, MR-pro-ANP, and NT-pro-BNP with outcomes were estimated using Cox regression analyses adjusted for established risk factors.
Results:
During a maximum follow-up of 6.5 years, 413 non-CV deaths, 179 CV deaths, 519 MACE, and 388 hospitalizations for HF were observed. In Cox regression analyses adjusted for established risk factors, each one of the 3 markers were associated with all the 4 outcomes, albeit the highest HRs were found for NT-pro-BNP. When models were extended to include all the 3 markers, NT-pro-BNP remained associated with all 4 outcomes. Conversely, from the 2 novel markers, associations remained only for Copeptin with non-CV death (HR, 1.62; 95% CI, 1.04-2.54 for highest vs lowest quintile) and with hospitalizations for HF (HR, 1.73; 95% CI, 1.08-2.75).
Limitations:
Single-point measurements of Copeptin, MR-pro-ANP, and NT-pro-BNP.
Conclusions:
In patients with moderately severe CKD, we confirm NT-pro-BNP to be strongly associated with all outcomes examined. As the main finding, the novel marker Copeptin demonstrated independent associations with non-CV death and hospitalizations for HF, and should therefore be evaluated further for risk assessment in CKD.
Plain-Language Summary:
A blood sample-based biomarker that indicates high cardiovascular risk in a patient with kidney disease would help to guide interventions and has the potential to improve outcomes. In 4,417 patients of the German Chronic Kidney Disease study, we assessed the relationship of Copeptin, pro-atrial natriuretic peptide, and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) with important outcomes over a follow-up period of 6.5 years. NT-pro-BNP was strongly associated with all of the 4 outcomes, including death unrelated to cardiovascular disease, death because of cardiovascular disease, a major cardiovascular event, and hospitalization for heart failure. Copeptin was associated with death unrelated to cardiovascular disease and hospitalization for heart failure. NT-pro-BNP and Copeptin are, therefore, promising candidates for a blood sample-based strategy to identify patients with kidney disease at high cardiovascular risk.
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