Investigators have identified 2 distinct acute kidney injury (AKI) subphenotypes with different risks for major adverse kidney events. The subphenotypes may improve risk stratification beyond using serum creatinine concentrations alone.

“Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology, and outcomes,” explained Pavan K. Bhatraju, MD, MSc, of the University of Washington in Seattle, and colleagues. “We incorporated plasma and urine biomarker measurements to identify AKI subgroups (subphenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes.”

In the ASSESS-AKI Study (Assessment, Serial Evaluation and Subsequent Sequelae), the investigators identified 29 plasma and urine biomarkers associated with AKI development. Latent class analysis and k-means clustering of the 29 variables revealed 2 AKI phenotypes. Class 1 patients had higher rates of pre-existing congestive heart failure and lower concentrations of plasma inflammatory and urinary tubular injury biomarkers. Class 2 patients had higher rates of pre-existing chronic kidney disease and higher concentrations of biomarkers.

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The investigators matched and compared 769 hospitalized adults with and 769 without AKI. The long-term risk for major adverse kidney events (MAKE) was 2.1- and 3.0-fold higher for patients with AKI class 1 and 2, respectively, compared with patients without AKI, Dr Bhatraju and colleagues reported in the American Journal of Kidney Diseases. The class 2 AKI group had a 1.4-fold increased risk for MAKE compared with the class 1 group, after adjustment for KDIGO AKI stage and other factors.

The higher risk of MAKE among class 2 patients was explained by a higher risk for chronic kidney disease (CKD) progression and dialysis, according to the investigators. The risk for CKD progression was a significant 3.0-fold higher with class 2 compared with class 1 AKI. The risk for dialysis initiation was a significant 4.6-fold higher with class 2 vs 1. Patients with AKI class 1 or 2 had significantly increased risks for CKD development and early death compared patients without AKI.

“Key variables that differentiated the AKI subphenotypes included host response markers of inflammation, such as sTNFR-1, IL-6, IL-10, and urinary markers of tubular injury and inflammation, such as urinary NGAL and IL-18,” Dr Bhatraju’s team revealed. Serum creatinine ranked 20th out of the 29 variables for differentiating classes 1 and 2. Urine output data were not available, which is a study limitation.

Class 2 patients may benefit from closer follow-up for early signs of CKD progression, according to the investigators. They noted that no effective pharmacotherapy currently exists for the prevention or treatment of AKI.

“Techniques that incorporate multidimensional patient data to improve our understanding of the heterogeneity of AKI in different patient populations could lead to precision guided approaches to patient care,” the authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Bhatraju PK, Prince DK, Mansour S, et al. Integrated analysis of blood and urine biomarkers to identify acute kidney injury subphenotypes and associations with long-term outcomes. Am J Kidney Dis. Published online April 10, 2023. doi:10.1053/j.ajkd.2023.01.449