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Laith Al-Rabadi Awarded Young Investigator Grant from National Kidney Foundation

Laith Al-Rabadi Awarded Young Investigator Grant from the National Kidney Foundation (NKF)

Dr. Laith Al-Rabadi, MD, has been awarded the Young Investigator Grant from the National Kidney Foundation (NKF) for his project, "Utah Kindred P Revisited" to raise awareness and create interest in the challenge of developing treatment for Alport syndrome and it's complications. The NKF established a Young Investigator grant program to support clinical research studies addressing important issues for patients with kidney disease. This is a one-year grant from July 1, 2019 to June 30, 2020. 

Utah Kindred P Revisited Overview

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 microhematuria (blood in the urine), and eventually as many as 40% of them develop end-stage renal disease (ESRD) and become dialysis- dependent. Moreover, age at ESRD differs between families and in males ranges between the second and third 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. 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 AS. A new imaging technology, called fluorescence lifetime imaging ophthalmoscopy (FLIO), has demonstrated promise for diagnosing various retinal diseases at early stages. Neither imaging study is routinely used to diagnose AS, and whether macular pathology correlates with genetic mutations or predicts progressive renal disease has never been studied.

Our overarching hypothesis is that (1) modifier genes contribute to expression of intra-familial variability and renal progression risk in patients with XLAS; (2) newer ophthalmologic approaches, specifically OCT and FLIO, (a) improve clinicopathologic correlations in XLAS and (b) correlate with renal disease progression risk.