PI name and affiliations Chi-yuan Hsu, MD, MSc; Professor and Chief, Division of Nephrology, University of California San Francisco (UCSF)

Potential Co-investigators Andrew Auerbach, MD; Professor, Division of Hospital Medicine, UCSF

Kathleen Liu, MD, PhD; Professor, Division of Nephrology, UCSF

Raymond Hsu, MD; Assistant Professor, Division of Nephrology, UCSF

Program overview/introduction We are interesting in improving the care of hospitalized patients with severe acute kidney injury (AKI), including those with AKI requiring acute dialysis (AKI-D). This is a high risk population and we and others have reported that incidence of AKI-D has increased over time in the U.S. (1)

Key clinical questions or evidence gaps Chronic kidney disease leads to erythropoietin deficiency. So erythropoiesis stimulating agents (ESA)(such as epoetin alfa [Procrit or Epogen] and darbepoetin alfa [Aranesp]) are routinely given to end-stage renal disease patients on dialysis to treat anemia. However whether AKI-D patients should receive ESA is unclear. ESA may be relatively ineffective in raising hemoglobin levels due to inflammation and other co-existing conditions among AKI-D patients.

Few studies have examined impact of ESA on hemoglobin levels, need for transfusion and other clinical or patient-oriented outcomes in patients with established AKI-D. Small observational studies have not suggested benefit in this population (2). Large clinical trials have showed that use of epoetin alfa did not reduce the incidence of red blood cell (RBC) transfusion among critically ill patients with and without AKI (and is associated with an increased thrombotic events)(3).

However, based on anecdotal evidence and preliminary single center studies (2), prescription of ESA among AKI-D patients is not uncommon. ESA’s are costly and are known to be associated with adverse outcomes such as thrombosis. Rigorously determining the risk-benefit ratio and cost-effectiveness of administering ESA in AKI-D is the long-term goal of our project.

Aims and Hypotheses Our short-term specific aim for this proposal is to determine the current patterns of ESA prescription for erythropoiesis stimulating agents across several health systems.

We hypothesize that there is currently great variation in practice pattern across health systems and among providers.

Any preliminary data None

Study design, including study subjects (patients and/or providers) and setting, comparator groups, data sources, outcomes, analysis plan, power and sample size, limitations, and timeline We propose a secondary analysis of data currently available from clinical data research network (CDRNs). The study design is cross-sectional (e.g. covering Jan-Dec 2016) and descriptive to start. We want to first understand the frequency of administration of ESA in patients with AKI-D; we can then examine the correlation between receipt of ESA and hemoglobin level and need for RBC transfusion in regression models (understanding confounding by indication and other analytic challenges)

Characteristics of sites who might participate Sites with reliable electronic medical records (EMR)(including pharmacy database) to capture ESA administration and PRBC transfusion; availability of basic lab tests such as serial hemoglobin levels and creatinine concentration; it would be good (although not necessary) if the system tracks which physician ordered the ESA (e.g. nephrologist or non-nephrologist; and whether different providers have different prescription patterns); we believe that current administrative codes are quite good at identifying patients who have AKI-D but details regarding how many hemodialysis sessions a patient underwent relative to ESA administration (vs. ESA given during days on continuous renal replacement therapy) would be helpful

Potential funders with RFA/RFP and due dates We believe that we can demonstrate considerable variation in prescription of ESA in AKI-D. This will justify conduct of more sophisticated observational studies regarding the effectiveness and cost-effectiveness of ESA in this setting. There likely is equipoise to justify conducting a randomized trial of whether or not ESA should be administered to AKI-D patients. NIH-NIDDK would be a potential funder.  If we included patient oriented outcomes, then PCORI may also be a potential funder.

REFERENCES

1. Hsu RK, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol 2013, 24: 37–42

2. Http://www.beaumontchildrenshospital.com/Global/Pharmacy/Rebecca%20Kurian_052014.pdf

3. Corwin HL, et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 2007, 357: 965-76.