Abstract: SA-PO0788
The Second Hit: Systemic Lupus Erythematosus and Sjögren Overlap Syndrome as a Trigger for APOL1-Associated Collapsing Glomerulopathy
Session Information
- Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
October 24, 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
- Pant, Abhishek, Stony Brook University Hospital, Stony Brook, New York, United States
- Ali, Selma, Stony Brook University Hospital, Stony Brook, New York, United States
- Khan, Sobia, Stony Brook University Hospital, Stony Brook, New York, United States
Introduction
Collapsing glomerulopathy (CG) is a rare and aggressive variant of focal segmental glomerulosclerosis characterized by segmental or global collapse of glomerular capillaries, podocyte hyperplasia, and prominent tubulointerstitial injury. Clinically, it presents with marked proteinuria and rapidly progressive kidney disease. We present a case of APOL1-associated CG in a patient with systemic lupus erythematosus (SLE)/Sjögren’s overlap syndrome.
Case Description
A 54-year-old African American woman with SLE/Sjögren’s overlap syndrome on prednisone and mycophenolate mofetil therapy (MMF), and CKD III presented with worsening renal function. Serum creatinine increased from a baseline of 2.0 mg/dL to 5.7 mg/dL over seven months. Urinalysis revealed new nephrotic-range proteinuria of 5.2 g/day without hematuria; prior proteinuria had been <500 mg/day. Immunologic studies were notable for positive ANA (1:1280), elevated SSA (>8), SSB (4.6), and anti-dsDNA (6 IU/ml) antibodies, low complement levels (C3 50 mg/dL, C4 9 mg/dL), and negative anti-Smith, anti-RNP antibodies. Hepatitis B, hepatitis C, HIV were negative. Genetic testing identified homozygous APOL1 G1 risk alleles. Kidney biopsy demonstrated collapsing glomerulopathy with pseudocrescent formation and microcystic tubular changes, consistent with APOL1-associated nephropathy. Mild mesangial proliferation and immune-complex deposition suggested Class II lupus nephritis without histologic features of active glomerulonephritis. Despite treatment with high-dose corticosteroids, MMF, and belimumab, renal function did not recover.
Discussion
Lupus nephritis (LN) and CG can be histologically difficult to distinguish, particularly in differentiating true cellular crescents from pseudocrescents. The absence of proliferative lupus features, together with microcystic tubular changes, supported APOL1-associated CG rather than active LN. In this case, SLE/Sjögren’s overlap syndrome potentially triggered APOL1 mediated injury. Evidence-based treatment options for CG are limited, and many patients progress to ESKD despite therapy. This case highlights the importance of evaluating genetic contributors beyond the apparent trigger to aid prognostication and familial risk counseling.