2021 Research Grant Recipients

Satellite Dialysis Clinical Investigator Grant

Risk-Based Care and Equity in Advanced Chronic Kidney Disease
Chi Chu, MD, The Regents of the University of California San Francisco; San Francisco, CA
The Kidney Failure Risk Equation (KFRE) is a simple and widely validated tool for predicting the risk of kidney failure among patients with chronic kidney disease (CKD). There is significant interest in using risk thresholds to guide clinical decisions, such as the timing of hemodialysis access placement for patients with advanced CKD. Little evidence exists regarding the predictive performance of the KFRE by race among patients with advanced CKD, although racial differences in CKD progression have been well documented. Differential prediction performance by race may contribute to racial disparities if predictions are used to drive clinical decisions. The proposed research seeks to evaluate the performance of the KFRE by race in a diverse cohort of patients with advanced CKD and to assess the potential for the KFRE to be used for decision making in advanced CKD.

NKF Young Investigator Grant

Utah Kindred P Revisted
Laith Al-Rabadi, MD, 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.
Pilot Intervention to Facilitate Care for Latinx Individuals with Proteinuria
Tessa Novick, MD, MSW, MHS, University of Texas at Austin Dell Medical School; Austin, TX
Latinx individuals with early kidney disease are more likely to progress to kidney failure, and at faster rates, than non-Latinx populations. Unique barriers often limit nephrology care, and many do not interact with the medical system until they are in kidney failure. We will adapt and pilot test an intervention to assess the acceptability and feasibility of using a community health worker to link Latinx individuals found to have protein in their urine at community screening events with medical care. The 6-month intervention will address barriers to care and facilitate improved kidney disease awareness and understanding. We also seek to culturally tailor kidney disease educational materials for use with Latinx populations. Findings will indicate the need for additional tailoring in preparation for a future randomized trial that tests the impact of the intervention on care linkage. This study will inform an intervention that could be paired with community screening efforts nation-wide.
The Role of RNA Editing in Apolipoprotein L-1 Regulation
Cristian Riella, MD, 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.

Joseph M. Krainin MD Memorial Young Investigator Award

Single Cell Transcriptomic Profile in the Diagnosis of Kidney Transplant Rejection
Rohan Paul, MD, George Washington University; Washington, DC
Kidney transplantation is the treatment of choice in patients with kidney failure. It improves the quality of life and mortality as compared to remaining on dialysis. Rejection is a normal reaction of the body to foreign tissue. The body sees the transplanted kidney as threat and tries to attack it by making antibodies against it and sending immune cells to destroy it. Identification of early symptoms of kidney rejection is performed through scheduled kidney biopsies in which tiny pieces of the transplanted kidney are taken and examined under a microscope. However, as an invasive method, kidney biopsy can have adverse consequences. To avoid any major or minor complications associated with the kidney biopsy, we propose to compare and generate the gene expression profiles in urinary cells and biopsy cells of kidney transplant patients. This study aims to identify gene expression signatures for kidney rejection in urinary cells as a surrogate for kidney biopsies.