2019 Research Grant Recipients

 

Project: Forecasting Deceased Donor Kidney Allograft Survival Using Machine Learning
Vishnu Potluri, University of Pennsylvania; Philadelphia, PA

 

Thousands of people donate their kidneys each year in the United States to help patients with kidney disease, unfortunately, nearly 20% of all kidneys recovered from donors after death are discarded, as they are thought to be of “poor quality.” Leading kidney organizations in the United States including the National Kidney Foundation have prioritized reducing kidney discard as one of their goals. But, an important barrier to understanding which kidneys to transplant and which ones to discard- is a limitation in our ability to accurately stratify the quality of deceased donor kidneys. Currently available research tools to predict the risk of kidney failure after transplantation while helpful, are not accurate, and there is concern that it might be contributing to the kidney discard. By harnessing improvements in data and research methodology, this project will utilize tools such as machine learning to improve our ability in predicting kidney function after transplantation.

 

 

Project: Utah Kindred P Revisited
Laith Al-Rabadi, University of Utah Hospital; Salt Lake City, UT

 

Alport syndrome (AS) is the second most common cause of inherited renal failure. It is characterized by progressive loss of renal function, hearing deficits, and ocular abnormalities. X-Linked Alport Syndrome (XLAS) is clinically and genetically heterogeneous. Contrary to common belief, female heterozygotes with a COL4A5 mutation are not asymptomatic carriers; they nearly always display micro hematuria, and eventually as many as 40% of them will develop end-stage renal disease (ESRD). Moreover, age at ESRD differs between families, and in males ranges between the third and fourth decades. However, in milder cases, ESRD may be delayed until the fifth or sixth decade and may not even occur in some cases. Distinguishing between mild cases and those that rapidly progress to ESRD is difficult, but it is critical for optimal clinical management.

 

A key barrier to providing personalized medical management is lack of understanding of genetic or clinical predictors of phenotypic severity associated with a given genetic mutation. One recent study used a candidate gene approach which suggested a possible role of modifier genes. Additionally, recent imaging studies have identified the importance of temporal macular thinning, detected by optical coherence tomography (OCT), in diagnosing and determining prognosis in patients with Alport syndrome. A new imaging technology, called fluorescence lifetime imaging ophthalmoscopy (FLIO), has demonstrated promise for diagnosing various retinal diseases at early stages.

 

Our goal is to apply the methods and data from this pilot study on a larger scale to validate our findings and continue to identify potential modifying genes and pathogenic pathways that may help describe clinical variability in phenotype expression. Identifying such factors could pave the way for new therapeutic approaches.

 

Project: The Role of RNA Editing in Apolipoprotein L-1 Regulation
Cristian Riella, Beth Israel Deaconess Medical Center; Boston, MA

 

African-Americans are four times more likely to develop kidney disease than Caucasians. This disparity is explained in part by mutations in the apolipoprotein L-1 (APOL1) gene. The mutations only occur in African Americans and increase the risk of kidney disease by up to 30 times. There is currently a gap in knowledge in how this gene works. In my preliminary work, I discovered a new mechanism of APOL1 control, which determines how much APOL1 protein is produced. Understanding this mechanism has the potential to identify new targets for future drug development. For example, in place of developing a drug that targets the defective protein, we will be able to develop a drug that stops the protein from being produced in the first place. Finally, unveiling how the protein is controlled is one step closer to understanding how it causes kidney disease, a question not yet answered.

 

 

Project: Isosorbide Mononitrate for Anti-Vascular Endothelial Growth Factor (VEGF) Induced Kidney Injury
Jaya Kala, University of Texas Science Center at Houston; Houston, TX

 

Recent advances in cancer chemotherapy has helped dramatically improve the outcome of cancer and overall prognosis. These have allowed the patients to live longer and healthier lives. Despite these great achievements, there are several occasions when patient have to suffer from side effects of these potent medications. One such side effect of the potent antiangiogenic medications, used for renal cell cancer, gastrointestinal cancers and lung cancers, are its effects on the kidneys. The anti-angiogenic drugs often cause acute kidney injury, protein in urine and hypertension. This is as a result of one of the actions of the drug where it reduces nitric oxide in the blood. We propose to use isosorbide mononitrate as a donor of nitric oxide to replete this deficiency. This will help improve the patient’s kidney functions, allowing the oncologist to continue using these lifesaving chemotherapeutic drugs without worrying about its effects on the kidneys.

 

 

Project: Identifying Barriers and Impacting Care in Chronic Kidney Disease Awareness
Manisha Singh, University of Arkansas for Medical Sciences; Little Rock, AR

 

Of about 450,000 Arkansans with chronic kidney disease (CKD), only 10% are aware that they have it. Primary-care providers (PCPs) are powerful partners for positive changes to protect kidney function and slow CKD progression since they encounter patients long before the nephrologists. However, CKD detection by PCPs is low, as also their awareness of the steps required to adequately manage CKD. In this study, we will assess the ability of checklists to create short and long-term knowledge gains in PCPs. We will also explore barriers that prevent optimized CKD care, including nephrology referrals. A 10 step checklist of CKD guidelines will be used to support PCP awareness and provide an outline for care.

 

This study is one facet of the overall goal to improve CKD awareness in Arkansas. The results of this study will inform the development of further study addressing an interactive CKD checklist to improve outpatient CKD care.