Abstract: SA-PO819
Rapidly Progressive Glomerulonephritis Due to Dense Deposit Disease Overlapping Alport Syndrome
Session Information
- C3G, TMA, MGRS, Amyloidosis, and More
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Author
- Sahota, Ruchi Jalota, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Introduction
Alport's syndrome is a rare X-linked mutation resulting in structural abnormalities in the glomerular basement membrane. C3 glomerulonephritis (C3GN), specifically dense deposit disease (DDD) is unique due to complement dysregulation of the alternative pathway. There are few cases reported of co-existance of Alport’s with DDD. We will be discussing a case of Alport’s syndrome complicated by rapidly progressive glomerulonephritis (RPGN) in the setting of DDD.
Case Description
21 year old male diagnosed with X-linked COL4A5 Alport’s variant admitted for hematuria, nephrotic range proteinuria, and elevated creatinine developed RPGN which resulted in the initiation of dialysis. Serology workup was negative for ANA, ANCA, anti-GBM, cryoglobulin, hepatitis, and HIV. Complements, Factor B and Factor H antigen were normal. Biopsy showed crescentic glomerulonephritis in setting of C3GN favoring DDD along with previous glomerular basement changes. Results were compatible with alternative pathway hyperactivation and C3GN was treated with Eculizumab as he had failed immmunosuppression and prednisone trial.
Discussion
Alport’s nephropathy has a broad range of progression from advanced age with normal kidney function to rapidly progressive renal failure depending on sex and COL4A genotype. Initial management for both Alport’s and C3GN require angiotensin-converting enzyme inhibitor (ACE-I); non-specific therapies include immunosuppressants, steroids, or plasmapheresis. Goal of the immunosuppression is to inhibit cellular immune response to decrease C3a and C5a production; early treatment with immunosuppression can have 100% renal recovery in C3GN. Currently, studies are ongoing for eculizumab and ravulizumab which bind with high affinity to C5 to prevent activation of MAC and C5a. This is one of the unique presentations where DDD occured upon Alport's and patient failed all conservative therapies, leaving renal transplant as the last option.