Personalizing Therapies for Acute Kidney Injury in Cirrhosis

PROJECT SUMMARY/ABSTRACT
Acute kidney injury is a devastating complication of cirrhosis (Cirr-AKI). Current Cirr-AKI guidelines
recommend all patients receive 1 g/kg/day of IV albumin for two days regardless of presenting features.
However, Cirr-AKI presents heterogeneously, often with overlapping causes of injury and evolving clinical
courses. Thus, this “one size fits all approach” may harm patients with pre-existing intravascular overload
and/or molecular features suggesting high risk of lung vascular leakage. Moreover, there is no guidance when
to stop albumin or how to define “adequate” repletion. Therefore, there is a critical unmet need for
personalizing resuscitation among Cirr-AKI patients to improve clinical outcomes and avoid complications of
volume overload. We approach this challenge with parallel and complementary aims. First, several studies
have shown that systemic inflammation and disruption of vascular integrity may be implicated in the
hemodynamic dysfunction of Cirr-AKI. Patients with less vascular inflammation may be more likely to respond
to albumin and less likely to be suffer adverse effects such as pulmonary edema due to capillary leak. Using
data and samples from two large and previously published biobanks, we will establish subphenotypes of Cirr-
AKI that respond well (or poorly) to established treatments using clinical, physiological, and molecular data.
Second, we aim to better define intravascular volume status using Point of Care Ultrasound (POCUS), an
emerging technique well-established in the critical care literature as an objective, reliable, and inexpensive tool
to gauge intravascular volume. Addition of this tool to current standard of care for Cirr-AKI may maximize the
chance of reaching euvolemia and/or reduce IV albumin administration to those already adequately
resuscitated or overloaded. We will perform a pilot trial assessing how a POCUS-guided treatment protocol
affects kidney outcomes and influences practice patterns around IV albumin prescription in Cirr-AKI.
Successful execution of these aims will illuminate new directions for diagnosis, therapeutic monitoring, and
tailored interventions for Cirr-AKI. In concert with training in trial design, vascular biology, and fostering a
national network of leaders in Cirr-AKI research, support from the K23 will enable a skill set that is applicable to
clinical trial work across the broader landscape of kidney injury, provide a springboard to an independent
academic career in nephrology, and build towards a multicenter collaborative network in a future R01 award.

Grant Number: 5K23DK128567-04
NIH Institute/Center: NIH
Principal Investigator: Andrew Allegretti