Circulating Proteins and Mortality in CKD: A Proteomics Study of the AASK and ARIC Cohorts.

Autor: Srialluri N; Department of Medicine, Johns Hopkins University, Baltimore, Maryland.; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland., Surapaneni A; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.; Division of Precision Medicine, Department of Medicine, New York University, New York, New York., Schlosser P; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland., Chen TK; Department of Medicine, Johns Hopkins University, Baltimore, Maryland.; Kidney Health Research Collaborative; Division of Nephrology, Department of Medicine, University of California San Francisco and San Francisco VA Health Care System, San Francisco, California., Schmidt IM; Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts., Rhee EP; Nephrology Division and Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts., Coresh J; Department of Medicine, Johns Hopkins University, Baltimore, Maryland.; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland.; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland., Grams ME; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.; Division of Precision Medicine, Department of Medicine, New York University, New York, New York.
Jazyk: angličtina
Zdroj: Kidney medicine [Kidney Med] 2023 Aug 14; Vol. 5 (10), pp. 100714. Date of Electronic Publication: 2023 Aug 14 (Print Publication: 2023).
DOI: 10.1016/j.xkme.2023.100714
Abstrakt: Rationale & Objective: Proteomics could provide pathophysiologic insight into the increased risk of mortality in patients with chronic kidney disease (CKD). This study aimed to investigate associations between the circulating proteome and all-cause mortality among patients with CKD.
Study Design: Observational cohort study.
Setting & Participants: Primary analysis in 703 participants in the African American Study of Kidney Disease and Hypertension (AASK) and validation in 1,628 participants with CKD in the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5.
Exposure: Circulating proteins.
Outcome: All-cause mortality.
Analytical Approach: Among AASK participants, we evaluated the associations of 6,790 circulating proteins with all-cause mortality using multivariable Cox proportional hazards models. Proteins with significant associations were further studied in ARIC Visit 5 participants with CKD.
Results: In the AASK cohort, the mean age was 54.5 years, 271 (38.5%) were women, and the mean measured glomerular filtration rate (GFR) was 46 mL/min/1.73 m 2 . The median follow-up was 9.6 years, and 7 distinct proteins were associated with all-cause mortality at the Bonferroni-level threshold ( P  < 0.05 of the 6,790) after adjustment for demographics and clinical factors, including baseline measured estimated GFR and proteinuria. In the ARIC visit 5 cohort, the mean age was 77.2 years, 903 (55.5%) were women, the mean estimated GFR was 54 mL/min/1.73 m 2 and median follow-up was 6.9 years. Of the 7 proteins found in AASK, 3 (β 2 -microglobulin, spondin-1, and N-terminal pro-brain natriuretic peptide) were available in the ARIC data, with all 3 significantly associated with death in ARIC.
Limitations: Possibility of unmeasured confounding. Cause of death was not known.
Conclusions: Using large-scale proteomic analysis, proteins were reproducibly associated with mortality in 2 cohorts of participants with CKD.
Plain-Language Summary: Patients with chronic kidney disease (CKD) have a high risk of premature death, with various pathophysiological processes contributing to this increased risk of mortality. This observational cohort study aimed to investigate the associations between circulating proteins and all-cause mortality in patients with CKD using large-scale proteomic analysis. The study analyzed data from the African American Study of Kidney Disease and Hypertension (AASK) study and validated the findings in the Atherosclerosis Risk in Communities (ARIC) Study. A total of 6,790 circulating proteins were evaluated in AASK, and 7 proteins were significantly associated with all-cause mortality. Three of these proteins (β 2 -microglobulin, spondin-1, and N-terminal pro-brain natriuretic peptide (BNP)) were also measured in ARIC and were significantly associated with death. Additional studies assessing biomarkers associated with mortality among patients with CKD are needed to evaluate their use in clinical practice.
(© 2023 The Authors.)
Databáze: MEDLINE
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