Analysis of Disease Progression in 769 Patients With Dominant Alport Syndrome
Author(s)
Vasily Aushev, PhD1, Dinah Clark, MS1, Stephen Andrews, PhD1, Alyssa Antonopoulos, MS1, Andrew Lazar, MD2.
1Natera, Austin, TX, USA, 2University Hospitals Case Medical Center, Cleveland, OH, USA.
1Natera, Austin, TX, USA, 2University Hospitals Case Medical Center, Cleveland, OH, USA.
OBJECTIVES: In this study we used Natera’s proprietary Real-World Database of patients with chronic kidney disease (CKD) tested with a broad renal genetic panel (RenasightTM) linked to Electronic Health Record (EHR) and closed claims data provided by Panalgo to evaluate progression of disease in patients molecularly identified with autosomal dominant Alport syndrome (ADAS).
METHODS: A retrospective analysis selected de-identified cases with one pathogenic or likely pathogenic variant in the COL4A3 or COL4A4 gene. Progression events were defined as an advance in CKD stage or a dialysis procedure. Age and stage-stratified real-world progression-free and dialysis-free survival (rwPFS;rwDFS) were calculated from earliest CKD stage to the subsequent event or dialysis procedure, respectively and Kaplan-Meier analyses were performed.
RESULTS: Of 3952 patients with ADAS, 769 (55.3% females, median age 52.3 y, COL4A3/COL4A4 in 47.5%/52.5% respectively) had at least one staging record with a median follow-up time of 22.5 months (IQR 35.5 months). CKD stage distribution at first timepoint was 12.2%, 17.6%, 45.7%, 10.8%, 13.7% for stages 1-5, respectively. Median rwPFS was 22.6 months, with no difference observed across age groups, and 52.9 and 7.2 months in stage 1 and 5, respectively. The 2-year rwPFS rate was 48.3% overall; 63.3%, 59.2%, 51.7%, 34.0%, 30.0% in stages 1-5 respectively. Median rwDFS overall was not reached given dialysis was recorded for <50% of the cohort. The 2-year rwDFS rate was 86.8% overall; 98.7%, 98.5%, 95.8%, 80.4%, 43.1% in stages 1-5 respectively.
CONCLUSIONS: This study demonstrates the value of incorporating real-world data with renal genetic test results in a CKD population by offering an approach to measure rwPFS and rwDFS. Future studies will expand these findings with lab values and additional endpoints, such as proteinuria, to further understand the natural progression of ADAS.
METHODS: A retrospective analysis selected de-identified cases with one pathogenic or likely pathogenic variant in the COL4A3 or COL4A4 gene. Progression events were defined as an advance in CKD stage or a dialysis procedure. Age and stage-stratified real-world progression-free and dialysis-free survival (rwPFS;rwDFS) were calculated from earliest CKD stage to the subsequent event or dialysis procedure, respectively and Kaplan-Meier analyses were performed.
RESULTS: Of 3952 patients with ADAS, 769 (55.3% females, median age 52.3 y, COL4A3/COL4A4 in 47.5%/52.5% respectively) had at least one staging record with a median follow-up time of 22.5 months (IQR 35.5 months). CKD stage distribution at first timepoint was 12.2%, 17.6%, 45.7%, 10.8%, 13.7% for stages 1-5, respectively. Median rwPFS was 22.6 months, with no difference observed across age groups, and 52.9 and 7.2 months in stage 1 and 5, respectively. The 2-year rwPFS rate was 48.3% overall; 63.3%, 59.2%, 51.7%, 34.0%, 30.0% in stages 1-5 respectively. Median rwDFS overall was not reached given dialysis was recorded for <50% of the cohort. The 2-year rwDFS rate was 86.8% overall; 98.7%, 98.5%, 95.8%, 80.4%, 43.1% in stages 1-5 respectively.
CONCLUSIONS: This study demonstrates the value of incorporating real-world data with renal genetic test results in a CKD population by offering an approach to measure rwPFS and rwDFS. Future studies will expand these findings with lab values and additional endpoints, such as proteinuria, to further understand the natural progression of ADAS.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
RWD67
Topic
Real World Data & Information Systems
Topic Subcategory
Health & Insurance Records Systems
Disease
SDC: Rare & Orphan Diseases, SDC: Urinary/Kidney Disorders