Tingting Li and Frank O’Brien Receive Inaugural Clinical Innovation Grants

Two research groups, headed by Tingting Li, MD, MSCI, and Frank O’Brien, MD, will be the first recipients of the Clinical Innovation Grants (CIG), the new funding program that provides resources for clinical research projects within the Division of Nephrology.

Dr. Tingting Li, Associate Professor of Medicine, Nephrology, will receive $38,038 to study Choroidal Thickness as a Novel Biomarker for Disease Activity in Lupus Nephritis.  Her collaborators, an inter-disciplinary team of rheumatologists, ophthalmologists, and a biostatistician,  include:  Iris Lee, MD, Rithwick Rajagopal, MD, PhD, Rajendra Apte, MD, PhD, Seth Eisen, MD, Alfred Kim, MD, PhD, and Yan Yan, MD, PhD.

Lupus nephritis (LN) is the inflammation of the kidney caused by systemic lupus erythematosus (SLE), an autoimmune disorder.  LN leads to end-stage renal disease in 30% of patients and is the most important predictor of SLE mortality.

While renal biopsy is the gold standard for initial LN diagnosis, repeat biopsies over the course of treatment to monitor therapeutic response is impractical.   What is needed in the management of LN is an accurate, noninvasive method to assess disease activity and response to therapeutic interventions.

The choroid, a dense capillary plexus in the eye, is biologically similar to the vasculature of the kidney.  In a preliminary study, Li and her team found that the health of the choroid informs the disease activity in the vasculature of the kidney.  They employed a method to measure choroidal thickness in lupus nephritis patients and found that lupus flare (a worsening of symptoms that signals increased disease activity) was associated with thicker choroid.

This method, a non-invasive imaging of the choroid, is a routine and easy-to-perform diagnostic test.  This study will evaluate the extent to which the choroid can serve as a novel and noninvasive biomarker for assessment of lupus nephritis activity.

Results of the study will have very important clinical implications in the understanding of the pathophysiology of lupus nephritis and the care of lupus patients.

Dr. Li has been involved with ongoing studies that examine risk factors, clinical course and long-term outcomes of lupus nephritis in a population of veterans, in collaboration with the St. Louis Veterans Affairs Clinical Epidemiology Center.   She recently completed the Masters of Science in Clinical Investigation program at Washington University examining the ability for International Classification of Diseases coding to correctly identify lupus nephritis patients in the Veteran’s Health Administration database.  Follow Dr. Li @Ting2li on Twitter.

Dr. Frank O’Brien, Assistant Professor of Medicine, Nephrology, will receive $17,468 to study The Effect of Intra-dialytic Potassium and Magnesium Fluctuations on Cardiovascular Functioning in ESRD Patients Undergoing In-center Hemodialysis.  His research team includes:  Michael Rauchman MD, Daniel Cooper, MD, Phyllis Stein, PhD, Andy Chuu, MD, and Amber Salter, PhD.

Cardiovascular disease is the most common cause of death in patients with end-stage renal disease (ESRD).  Clinically significant arrhythmias are common in hemodialysis patients, and may contribute to sudden cardiac death.  As well, decreased or abnormal heart rate variability (HRV), a measure of cardiac autonomic function, is a risk factor for cardiovascular morbidity/mortality and sudden cardiac death in the non-ESRD population, but has not been well studied in the hemodialysis population.

Pre-dialysis hypo- or hyperkalemia correlate with increased morbidity and mortality in the ESRD population.  These abnormal serum potassium levels are believed to contribute to increased rates of sudden cardiac death, likely in the presence of fatal brady or tachyarrhythmias. In addition, fluctuations of electrolytes, including magnesium and potassium have previously been identified as potential risks for generation of arrhythmias.

The relationship between changes in potassium, magnesium and either arrhythmia generation or HRV during hemodialysis has not previously been explored.  Dr. O’Brien’s study will explore the relationship between serum potassium and magnesium fluctuations and cardiovascular functioning in approximately 30 ESRD patients undergoing in-center hemodialysis.

Plasma potassium and magnesium levels will be measured pre and post dialysis, and every 30 minutes for the duration of the first weekly dialysis session.  Holter monitors will be placed on the patient pre-dialysis and will record ECG signals continuously for the following 96 hours. The monitor will be removed at the end of their third dialysis session of the week.   The Holter monitor data will be analyzed for arrhythmias and HRV for each day of the recording.

Data from this pilot study will help define the relationship between changes in intra-dialytic potassium, magnesium and either arrhythmia generation or HRV in ESRD patients and will help in the design of larger, future studies.

“We hope the results from this study will help personalize hemodialysis treatments for our patients and help improve the care we provide for them,” says Dr. O’Brien.

Dr. O’Brien has been directly involved in the effort of the Division of Nephrology to reduce the number of hospital readmissions among its dialysis patients.  See the cover article in the division’s Spring 2019 Newsletter here.  He is also involved with ongoing studies aiming to improve care among our ESRD patient population.

As Dr. Andy Chuu, one of the collaborators, announced on Twitter, “Study Holter Monitors have arrived! A lot smaller than I would have imagined. Excited to finally start our ESRD dysrhythmia study!”

Follow Frank O’Brien @frankjobrien84, Andy Chuu @ChuuAndy, and the Division of Nephrology @WUNephrology on Twitter.