Acute Kidney Injury following Cardiac Surgery: A Clinical Model

Abstract

Background: Scientists use preclinical models of acute kidney injury (AKI) to decipher mechanisms and develop therapy, but translation of therapies to patients remains poor. Models that better resemble patients, including those within clinical care, should be considered.

Summary: Mice provide many advantages to the study of human disease including an ability to dictate precise experimental conditions. To best isolate and measure phenomena, scientists reduce experimental variability - identical animals, environmental conditions, experimental exposures, and outcome assessments. This technique reduces effect size variability and increases power but dissociates these model organisms from the clinical patients they intend to represent, potentially accounting for the poor translation of findings into patient care. Clinical research, conversely, is often plagued by heterogeneous patients, heterogenous environmental factors, and heterogenous renal insults. A compromise between these 2 extremes - a model of AKI that is more similar to human disease but still provides opportunities for rigorous investigation - should be utilized. Cardiac surgery provides a clinical model for the study of AKI due to mechanism overlap it shares with other clinical conditions (improved generalizability) and characteristics that provide distinct opportunities for research. The high rate of AKI following cardiac surgery and the relative homogeneity (decreased variability) of cardiac surgery subjects, their environment, and renal insults increase power and the opportunity to make discoveries and advance care. Moreover, the elective nature of cardiac surgery provides opportunities to perform detailed baseline assessments and pretreat select patients. Key Messages: Models that better reflect clinical AKI are needed to decipher mechanisms and develop effective treatments. Cardiac surgery is an important clinical model form for the study of AKI.

Keywords: Acute kidney injury; Cardiac surgery; Clinical model; Mouse model; Statistical power.

Fig. 1.

Characteristics of cardiac surgery that increase statistical power and are favorable for its use as a model for the study of acute kidney injury (AKI) in humans. AKI, acute kidney injury.