Abstract: FR-PO0709
A Double-Edged Sword: Gene Therapy as a Potential Second-Hit for APOL1-Mediated Kidney Disease
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- McNaughton, Lauren Maryse, Nationwide Children's Hospital, Columbus, Ohio, United States
- Gartstein, Evelyn C., Nationwide Children's Hospital, Columbus, Ohio, United States
- Rangarajan, Hemalatha, Nationwide Children's Hospital, Columbus, Ohio, United States
- Bignall, O. N. Ray, Nationwide Children's Hospital, Columbus, Ohio, United States
Introduction
Over seven million individuals globally live with sickle cell disease (SCD), a group of hemoglobinopathies with significant systemic and end organ effects. Patients with SCD are at increased risk for sickle cell nephropathy (SCN), including focal segmental glomerulosclerosis (FSGS). In individuals of sub-Saharan African ancestry, co-inheritance of high-risk Apolipoprotein 1 (APOL1) alleles may further increase susceptibility to progressive chronic kidney disease (CKD), known as APOL1 mediated kidney disease (AMKD). Although curative gene therapies (GT) for SCD are transforming clinical outcomes, their impact on kidney health in genetically susceptible individuals remains poorly understood.
Case Description
In this case report we discuss a 21-year-old patient with SCD who was referred to nephrology six months following GT after his eGFR declined from a baseline of 131 ml/min/1.73m2 to 75 ml/min/1.73m2 along with nephrotic range proteinuria and hypertension. Subsequent diagnostic evaluation revealed SCN, kidney biopsy-confirmed glomerulosclerosis (pictured), genetic testing revealing two high-risk alleles for APOL1, and AMKD. Despite management with Angiotensin II Receptor Blocker (ARB) and Sodium Glucose Co-Transporter 2 (SGLT-2) inhibitor therapies, his renal function could not be salvaged.
Discussion
We hypothesize that this patient’s AMKD was caused by a “second-hit” from underlying SCD, the stress of GT, or both. We consider the increased risk GT may pose for AMKD in this patient population weighed together with the transformative benefits of curative therapy for SCD. Ultimately, this case emphasizes the importance of collaboration between nephrology and hematology for patients with SCD and the value of implementing standardized practices for early identification, referral, and management of individuals with evidence of SCN to optimize care.
Acknowledgment
We would like to thank Drs. Susan Creary, Keisha Gibson, Shamlal Mangray, Keia Sanderson, and Anthony Villella. We would also like to thank our patient and his family for their contributions.