Acute Kidney Injury and eResearch

Emily Joyce, MD, joined the Division of Pediatric Nephrology in July 2017 after completing her residency and fellowship training at UPMC Children’s Hospital of Pittsburgh. Dr. Joyce’s research is focused on understanding the associations between medications — those that are or may potentially be nephrotoxic — and acute kidney injuries (AKI) in critically ill children receiving treatment in the intensive care unit. AKI rates in children during treatment for critical illness are approximately 25 percent, making for a high prevalence among a susceptible patient population and leading to both short- and long-term adverse effects on patient health. Dr. Joyce has developed, in collaboration with her mentor John Kellum, MD, from the University of Pittsburgh Department of Critical Care Medicine, a high-density intensive care patient database of critically ill children that includes data points on more than 12,000 patient encounters over a five-year period, from 2010 to 2014. Dr. Joyce is using the database to understand the associations between the administration of certain medications and AKI to better determine risk stratification and how the risk of AKI can be minimized in certain medication scenarios. Dr. Joyce’s initial investigations are probing antibiotics and antibiotic combinations associated with AKI in critical illness, particularly the use of the broad-spectrum antibiotic vancomycin — alone, and in combination with other agents, including piperacillin and tazobactam.

Recently, she and Dr. Kellum and colleagues published a paper in the journal Nephrology Dialysis Transplantation which outlines some of the electronic health record research and applications they have been able to derive from their database. They also describe methodologies for how eResearch in AKI can be conducted based on their experiences and pilot projects using the data to transform clinical practice.

Leveraging eResearch to Study AKI — Experiences and Learnings

One of Dr. Joyce and colleagues’ first published papers outlining their use of the critically ill patient database to study AKI recounts how the database for studying AKI was conceived and built, and lays out for the first time a methodology for eResearch for studying aspects of acute kidney injury.

“Our goal with this paper was to describe some ideal methods for large database research in AKI, using some of our preliminary work as illustrative examples. One of our projects that is discussed in the paper describes our work to identify and stage acute kidney injury and the exposures and outcomes related to it based on the consensus definition of AKI that was established by the Kidney Disease: Improving Global Outcomes (KDIGO) guideline several years ago,” says Dr. Joyce.

Collaborative Investigations in Progress

Since developing her AKI database in collaboration with Dr. Kellum, Dr. Joyce has worked with several other members of the Division of Pediatric Nephrology on projects that have been able to utilize the database. Colleagues Michael L. Moritz, MD, FAAP, clinical director of the Division, and Cassandra Formeck, MD, a third-year fellow, presented a study in poster format at the 2018 American Society of Nephrology Kidney Week annual meeting. The study is investigating the role of hyponatremia as a risk factor for development of AKI, and hyponatremia as a risk factor for development of sepsis.

In another study with Dr. Formeck and Dr. Kellum, AKI is examined as a risk factor for infection in patients who are critically ill. This research is evaluating a number of infection types — pneumonia, urinary tract infection, sepsis, and others — for which AKI may be a risk factor.

“Recently, I’ve teamed up with Dana Fuhrman, DO, MS, a researcher in our Division who is also interested in aspects of acute kidney injury, and Elisa Heipertz, MD, a resident interested in critical care medicine, on a new epidemiological study. We have become interested in the development of AKI after solid organ transplants and stays in the ICU,” says Dr. Joyce.

“With Dr. Fuhrman, we are doing another small study looking at the incidence of short- and long-term kidney outcomes in patients with congenital heart disease. Because our database contains cardiac intensive care unit (CICU) patient data, it’s a population we are able to study that by and large has not received a lot of attention. Finally, alongside one of our fellows, Christine Crana, MD, we’ve started a small project to validate a severity-of-illness score in our AKI database. All this work is very preliminary, but we’re excited at the prospects of contributing new knowledge to the field, and I’m very excited to be able to collaborate with other members of the Division to use the AKI database we have created.”

K23 Young Investigator Proposal

In 2018, Dr. Joyce submitted a proposal to the National Institutes of Health for a K23 Young Investigator grant. Part of Dr. Joyce’s proposal entails tracking pediatric patients who are exposed to specific types of nephrotoxic medications during treatment for a critical illness in a long-term follow-up scheme.

“It is my conjecture that we are not identifying a percentage of children who are at a high risk for the development of chronic kidney disease (CKD) — those children who have been critically ill or have developed CKD after they experienced an episode of acute kidney injury. My K23 proposal entails a short-term goal of conducting a feasibility study where a small cohort of these patients are brought back at defined intervals over a three-year period to monitor their kidney function and blood pressure,” says Dr. Joyce.

Longer-term, Dr. Joyce’s proposal would follow formerly critically ill children who are at high risk for developing CKD in an attempt at devising an early identification methodology that could lead to the ability to mitigate the long-term effects of exposure to critical illness and related AKI.

"It is my hope that this kind of research and intervention can augment and improve patient and family awareness relative to their increase in risk for chronic kidney disease after an episode of AKI. I think educating the parents and the patients, and monitoring them, could be incredibly beneficial for their long-term renal health,” says Dr. Joyce.

Dr. Joyce will likely have her proposal scored sometime during 2019 by the NIH. Until then, she is continuing with her other collaborative studies and eResearch on aspects of chronic kidney disease, AKI, and their intimately entwined relationship.

References and Further Reading

Joyce EL, DeAlmeida DR, Fuhrman DY, Priyanka P, Kellum JA. eResearch in Acute Kidney Injury: A Primer for Electronic Health Record Research. Nephrol Dial Transplant. 2018. Doi: 10.1093/ndt/gyf052. Epub ahead of print.