Lakhmir S Chawla1. 1. Department of Anesthesiology and Critical Care Medicine and Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington DC 20037, USA. minkchawla@gmail.com
Abstract
PURPOSE OF REVIEW: Acute kidney injury (AKI) is a clinical syndrome with many different causes. The Kidney Disease: Improving Global Outcomes consensus AKI definition has harmonized the study of AKI, yet effective clinical therapeutics are not available to treat most cases of AKI. In order to develop therapeutic interventions, an approach to AKI that subdivides the various causes of AKI into well codified subclasses of AKI may allow a process of 'disentanglement'. RECENT FINDINGS: Similar to the successful approach used in oncology, disentanglement refers to a process wherein various subtypes of a disease are inventoried (e.g., 10 subclasses of breast cancer). The various panels of sorted subtypes are then analyzed to determine whether there are similar pathophysiologic processes that are related to outcomes. Candidate therapeutics that mitigate these pathways are then tested in clinical trials in the corresponding subtypes to improve outcomes. Each successive step further clarifies which of the therapeutics is successful or not successful within each subclass of disease. SUMMARY: Disentangling the AKI syndrome requires an approach of rigorous taxonomy, molecular diagnostics, and intense collaboration. This approach may be applied to other complex and heterogeneous syndromes like sepsis and acute respiratory distress syndrome as well, but this article only outlines this approach to AKI.
PURPOSE OF REVIEW: Acute kidney injury (AKI) is a clinical syndrome with many different causes. The Kidney Disease: Improving Global Outcomes consensus AKI definition has harmonized the study of AKI, yet effective clinical therapeutics are not available to treat most cases of AKI. In order to develop therapeutic interventions, an approach to AKI that subdivides the various causes of AKI into well codified subclasses of AKI may allow a process of 'disentanglement'. RECENT FINDINGS: Similar to the successful approach used in oncology, disentanglement refers to a process wherein various subtypes of a disease are inventoried (e.g., 10 subclasses of breast cancer). The various panels of sorted subtypes are then analyzed to determine whether there are similar pathophysiologic processes that are related to outcomes. Candidate therapeutics that mitigate these pathways are then tested in clinical trials in the corresponding subtypes to improve outcomes. Each successive step further clarifies which of the therapeutics is successful or not successful within each subclass of disease. SUMMARY: Disentangling the AKI syndrome requires an approach of rigorous taxonomy, molecular diagnostics, and intense collaboration. This approach may be applied to other complex and heterogeneous syndromes like sepsis and acute respiratory distress syndrome as well, but this article only outlines this approach to AKI.
Authors: Rajit K Basu; Hector R Wong; Catherine D Krawczeski; Derek S Wheeler; Peter B Manning; Lakhmir S Chawla; Prasad Devarajan; Stuart L Goldstein Journal: J Am Coll Cardiol Date: 2014-12-30 Impact factor: 24.094