Abstract: FR-PO925
Importance of Integrating Clinical, Serological, Morphological, and Genetic Data to Optimize Care and Prognostication for Patients with Glomerular Diseases
Session Information
- Glomerular Diseases: Potpourri
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Co, Thien Kim Nguyen, Harbor-UCLA Medical Center, Torrance, California, United States
- Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States
- Dai, Tiane, Harbor-UCLA Medical Center, Torrance, California, United States
- Peretz, Ryan, Harbor-UCLA Medical Center, Torrance, California, United States
- Adler, Sharon G., Harbor-UCLA Medical Center, Torrance, California, United States
Introduction
KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Disease states that kidney biopsy is not needed to confirm the diagnosis for patients with nephrotic range proteinuria and a positive anti-PLA2R antibody test, especially if kidney function is normal or if there are contraindications. Our case highlights the importance of integrating clinical information, kidney biopsy findings, serologies, and genetics in patients whose clinical course do not progress as expected.
Case Description
A 63-year-old male with diabetes mellitus type 2 (DM), hypertension and hyperlipidemia was referred for nephrotic range proteinuria (4,311 mcg/mg). Serological evaluation was negative except for positive anti-PLA2R antibody with negative urine/serum protein electrophoresis, Hepatitis B, Hepatitis C, HIV, and RPR. Kidney size was normal. Urine sediment was inactive. Kidney biopsy showed membranous nephropathy (PLA2R positive), focal and segmental glomerulosclerosis with glomerulomegaly, features suggestive of renal vein thrombosis, and mild to moderate arterio- and arteriolosclerosis. Imaging ruled out venous thrombosis. He was treated with Rituximab and steroids, attaining complete serological remission with negative anti-PLA2R antibody after 9 months. However, 12 months after serologic remission, he had persistent proteinuria of ~2-3g, suggesting a secondary process. Given the FSGS with glomerulomegaly, genetic testing was performed (Natera Renasight) which identified a heterozygous likely pathogenic variant in the gene COL4A3 mutation; pathogenic variants in COL4A3 are associated with Alport Syndrome with either autosomal dominant or recessive inheritance patterns. Audiological evaluation revealed reduced hearing. Ophthalmological evaluation is pending.
Discussion
If a kidney biopsy was not pursued, the persistent proteinuria might have been attributed to secondary FSGS or DM. However, the biopsy findings led to genetic testing, which revealed concern for concomitant Alport syndrome. This case underscores the importance of integrating clinical, serological, histological, and genetic information to evaluate an unexpected clinical course. With these advances, we aim to tailor medical therapy and genetic counseling to address each patient’s unique clinical picture.