Molecular Subtypes Linked to Outcomes in Acute Kidney Injury

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Two molecular sub-phenotypes perform differently in response to vasopressin therapy.
Two molecular sub-phenotypes perform differently in response to vasopressin therapy.

(HealthDay News) -- Two molecularly distinct sub-phenotypes of acute kidney injury (AKI) are associated with different clinical outcomes and response to vasopressin therapy, according to a study recently published in the American Journal of Respiratory and Critical Care Medicine.

Pavan K. Bhatraju, MD, from University of Washington in Seattle, and colleagues developed a model to identify AKI sub-phenotypes and assess whether these sub-phenotypes have prognostic and therapeutic implications. The model was then applied to 271 patients with AKI in the Vasopressin in Septic Shock clinical trial.

The researchers found that a 2-sub-phenotype latent class analysis model had the best fit in both the discovery (P=0.004) and replication (P=0.004) cohorts. With AKI sub-phenotype 2 (AKI-SP2), the risk for 7-day renal nonrecovery and 28-day mortality was greater vs AKI sub-phenotype 1 (AKI-SP1). Compared with the Kidney Disease Improving Global Outcomes Stages of AKI, the AKI sub-phenotypes better discriminated risk for poor clinical outcomes. Including markers of endothelial dysfunction and inflammation in a 3-variable model accurately determined sub-phenotype classification. Compared with norepinephrine, vasopressin was associated with improved 90-day mortality in AKI-SP1 (27 vs 46%; P=0.02), but not in AKI-SP2 (45 vs 49%; P=0.99).

"Identification of AKI sub-phenotypes could improve risk prognostication and may be useful for predictive enrichment in clinical trial," the authors write.

Reference

Bhatraju PK, Zelnick LR, Herting J, et al. Identification of Acute Kidney Injury Sub-phenotypes with Differing Molecular Signatures and Response to Vasopressin Therapy. Am J Crit Care Med. DOI: 10.1164/rccm.201807-1346OC

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