Dialysis-requiring acute kidney injury (AKI-D) is a devastating complication among hospitalized patients for which there are no treatments other than supportive care. Recovery of sufficient renal function to stop dialysis is an unequivocally important clinical and patient-oriented outcome. Shortening dialysis duration and increasing the number of AKI-D patients who recover would have a major clinical, public health and cost-saving impact. However, there is currently no evidence to guide the delivery of dialysis to facilitate recovery. We hypothesize that in patients who have AKI-D and who are hemodynamically stable, a conservative dialysis strategy--in which hemodialysis is not continued unless specific metabolic or clinical indications for RRT are present--will improve the likelihood of renal recovery compared with the current standard clinical practice of thrice-weekly intermittent dialysis. We have conducted a pilot clinical trial to demonstrate the feasibility of this approach. We propose here a 2-center randomized controlled trial to test our conservative dialysis strategy in a larger AKI-D population (N = 220). To shed insight into potential pathophysiological mechanisms, we will examine the impact of the conservative dialysis strategy on not only clinical outcomes but also markers of renal tubular injury and systemic inflammation.
Our specific aims are:
Aim 1 : In hospitalized patients with AKI-D, to test whether a conservative dialysis strategy (compared with a standard thrice-weekly acute dialysis strategy): a. Increases the proportion of patients with renal recovery at hospital discharge--the primary outcome for this trial (defined as being alive and off dialysis at the time of discharge, with sustained independence from dialysis for 14 days which may occur in or out of the hospital); b. Reduces the number of dialysis sessions/week; c. Increases the number of dialysis-free days to study day 28 (days alive and not dependent on dialysis, similar to ventilator-free days).
Aim 2 : To determine the impact of a conservative dialysis strategy (compared with a standard thrice-weekly acute dialysis strategy) on renal tubular injury and systemic inflammation. Renal tubular injury will be reflected by plasma neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels during the first week of the study intervention. Systemic inflammation will be reflected by plasma interleukin [IL]-6, IL-8, IL-18 and soluble tumor necrosis factor receptor-1 levels. In aggregate, the studies proposed here are the next step towards changing the paradigm of dialytic management in patients with prevalent AKI-D and improving clinical outcomes in this vulnerable population.

Public Health Relevance

Acute kidney injury requiring dialysis is a devastating complication among hospitalized patients. There are currently no proven therapies to improve recovery of kidney function so that more patients can come off dialysis. We propose here a 2-center randomized controlled trial (N = 220) to test whether less frequent hemodialysis will improve the likelihood of renal recovery compared with the current standard clinical practice of thrice-weekly intermittent dialysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK122797-02
Application #
10015269
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Schulman, Ivonne Hernandez
Project Start
2019-09-11
Project End
2024-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118