Laith F. Al-Rabadi, MD
Division of Nephrology

CTSA Inter-Institutional Pilot Project Award
Assessing Autosomal Recessive Alport by DNA variants and Novel Ophthalmic Approaches
8/01/2018 – 7/30/2019

Alport syndrome (AS) is the second most common cause of inherited renal failure, characterized by progressive loss of renal function, hearing deficits, and ocular abnormalities. AS is caused by mutations in the type IV collagen genes, most commonly involving the alpha-5 chain type IV collagen (COL4A5) in X-linked inheritance. Less common genetic types of AS include autosomal recessive AS (ARAS) or autosomal dominant (ADAS) due to mutations in the alpha-3 or alpha-4 chains (COL4A3 or COL4A4). Individuals with heterozygous COL4A3 or COL4A4 mutations usually have thin basement membrane nephropathy (TBMN), a typically benign condition without renal impairment. Some TBMN patients, however, develop renal impairment with overlapping lesions of focal segmental glomerulosclerosis (FSGS). Distinguishing between AS and TBMN that progresses to FSGS is difficult, but it is critical for optimal clinical management.

This is a pilot project to establish a series of future studies of autosomal recessive Alport syndrome (ARAS) at the University of Utah. Our goal is to apply the methods and data from this pilot study on a larger scale to identify potential modifying genes and pathogenic pathways that may help describe clinical variability in phenotype expression. In addition, the use of newer ocular findings in patients with ARAS in our study is significant for the following reasons. (1) It may help differentiate ARAS from thin basement membrane nephropathy (TBMN) beyond genetic testing, (2) This is the first study that implements new ophthalmologic tools, fluorescence lifetime imaging ophthalmoscopy (FLIO) in conjunction with optical coherence tomography (OCT), in ARAS syndrome to systematically assess if the macular findings correlate with and/or predict renal failure risk. Our results may also help guide our evaluation of family members who are potential donors and possibly change the current policy of determining eligibility. 

Benjamin Steinberg, MD
Division of Cardiovascular Medicine

National Heart, Lung, and Blood Institute
Optimizing Outcomes for Patients with Heart Failure and Atrial Fibrillation – K23
07/01/2018 – 06/30/2023

This award will leverage the unique infrastructure of the mEval system at the University of Utah, in order to understand patient reported outcomes (PROs) and heterogeneity of treatment effects among patients with heart failure and atrial fibrillation. This work will build on the groundbreaking results of the CASTLE-AF study, a pivotal trial of catheter ablation in these patients that was led by the University of Utah.