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.