TY - JOUR
T1 - Joint Modeling of Clinical and Biomarker Data in Acute Kidney Injury Defines Unique Subphenotypes with Differing Outcomes
AU - Vasquez-Rios, George
AU - Oh, Wonsuk
AU - Lee, Samuel
AU - Bhatraju, Pavan
AU - Mansour, Sherry G.
AU - Moledina, Dennis G.
AU - Gulamali, Faris F.
AU - Siew, Edward D.
AU - Garg, Amit X.
AU - Sarder, Pinaki
AU - Chinchilli, Vernon M.
AU - Kaufman, James S.
AU - Hsu, Chi Yuan
AU - Liu, Kathleen D.
AU - Kimmel, Paul L.
AU - Go, Alan S.
AU - Wurfel, Mark M.
AU - Himmelfarb, Jonathan
AU - Parikh, Chirag R.
AU - Coca, Steven G.
AU - Nadkarni, Girish N.
N1 - Publisher Copyright:
Copyright © 2023 by the American Society of Nephrology.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - BACKGROUND: AKI is a heterogeneous syndrome. Current subphenotyping approaches have only used limited laboratory data to understand a much more complex condition. METHODS: We focused on patients with AKI from the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI). We used hierarchical clustering with Ward linkage on biomarkers of inflammation, injury, and repair/health. We then evaluated clinical differences between subphenotypes and examined their associations with cardiorenal events and death using Cox proportional hazard models. RESULTS: We included 748 patients with AKI: 543 (73%) of them had AKI stage 1, 112 (15%) had AKI stage 2, and 93 (12%) had AKI stage 3. The mean age (±SD) was 64 (13) years; 508 (68%) were men; and the median follow-up was 4.7 (Q1: 2.9, Q3: 5.7) years. Patients with AKI subphenotype 1 ( N =181) had the highest kidney injury molecule (KIM-1) and troponin T levels. Subphenotype 2 ( N =250) had the highest levels of uromodulin. AKI subphenotype 3 ( N =159) comprised patients with markedly high pro-brain natriuretic peptide and plasma tumor necrosis factor receptor-1 and -2 and low concentrations of KIM-1 and neutrophil gelatinase-associated lipocalin. Finally, patients with subphenotype 4 ( N =158) predominantly had sepsis-AKI and the highest levels of vascular/kidney inflammation (YKL-40, MCP-1) and injury (neutrophil gelatinase-associated lipocalin, KIM-1). AKI subphenotypes 3 and 4 were independently associated with a higher risk of death compared with subphenotype 2 and had adjusted hazard ratios of 2.9 (95% confidence interval, 1.8 to 4.6) and 1.6 (95% confidence interval, 1.01 to 2.6, P = 0.04), respectively. Subphenotype 3 was also independently associated with a three-fold risk of CKD and cardiovascular events. CONCLUSIONS: We discovered four AKI subphenotypes with differing clinical features and biomarker profiles that are associated with longitudinal clinical outcomes.
AB - BACKGROUND: AKI is a heterogeneous syndrome. Current subphenotyping approaches have only used limited laboratory data to understand a much more complex condition. METHODS: We focused on patients with AKI from the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI). We used hierarchical clustering with Ward linkage on biomarkers of inflammation, injury, and repair/health. We then evaluated clinical differences between subphenotypes and examined their associations with cardiorenal events and death using Cox proportional hazard models. RESULTS: We included 748 patients with AKI: 543 (73%) of them had AKI stage 1, 112 (15%) had AKI stage 2, and 93 (12%) had AKI stage 3. The mean age (±SD) was 64 (13) years; 508 (68%) were men; and the median follow-up was 4.7 (Q1: 2.9, Q3: 5.7) years. Patients with AKI subphenotype 1 ( N =181) had the highest kidney injury molecule (KIM-1) and troponin T levels. Subphenotype 2 ( N =250) had the highest levels of uromodulin. AKI subphenotype 3 ( N =159) comprised patients with markedly high pro-brain natriuretic peptide and plasma tumor necrosis factor receptor-1 and -2 and low concentrations of KIM-1 and neutrophil gelatinase-associated lipocalin. Finally, patients with subphenotype 4 ( N =158) predominantly had sepsis-AKI and the highest levels of vascular/kidney inflammation (YKL-40, MCP-1) and injury (neutrophil gelatinase-associated lipocalin, KIM-1). AKI subphenotypes 3 and 4 were independently associated with a higher risk of death compared with subphenotype 2 and had adjusted hazard ratios of 2.9 (95% confidence interval, 1.8 to 4.6) and 1.6 (95% confidence interval, 1.01 to 2.6, P = 0.04), respectively. Subphenotype 3 was also independently associated with a three-fold risk of CKD and cardiovascular events. CONCLUSIONS: We discovered four AKI subphenotypes with differing clinical features and biomarker profiles that are associated with longitudinal clinical outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85163908513&partnerID=8YFLogxK
U2 - 10.2215/CJN.0000000000000156
DO - 10.2215/CJN.0000000000000156
M3 - Article
C2 - 36975209
AN - SCOPUS:85163908513
SN - 1555-9041
VL - 18
SP - 716
EP - 726
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
IS - 6
ER -