Abstract: PO1553
Early Recurrence of C3 Glomerulopathy (C3G) in the Allograft
Session Information
- Glomerular Diseases: Clinical Features and Outcomes in Nephrotic Syndromes and Complement-Mediated Diseases
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Peleg, Yonatan A., Columbia University Irving Medical Center, New York, New York, United States
- Robbins-Juarez, Shelief, Columbia University Irving Medical Center, New York, New York, United States
- Chang, Jae Hyung, Columbia University Irving Medical Center, New York, New York, United States
- Crew, Russell J., Columbia University Irving Medical Center, New York, New York, United States
- Cohen, David J., Columbia University Irving Medical Center, New York, New York, United States
- Dube, Geoffrey K., Columbia University Irving Medical Center, New York, New York, United States
- Husain, Syed Ali, Columbia University Irving Medical Center, New York, New York, United States
- Mohan, Sumit, Columbia University Irving Medical Center, New York, New York, United States
- Morris, Heather K., Columbia University Irving Medical Center, New York, New York, United States
- Batal, Ibrahim, Columbia University Irving Medical Center, New York, New York, United States
- Bomback, Andrew S., Columbia University Irving Medical Center, New York, New York, United States
Background
C3G encompasses both C3 glomerulonephritis (C3GN) and Dense Deposit Disease (DDD), a rare group of kidney diseases associated with alternative complement pathway dysregulation that commonly recurs in the allograft. How early recurrence occurs is underexplored.
Methods
We reviewed cases of recurrent C3G in the allograft at CUIMC. Protocol biopsies were encouraged for transplanted C3G patients (PTS) at 6 months if a for-cause biopsy (bx) had not already been performed. Median (range) reported.
Results
13 PTS (9 C3GN, 4 DDD) were included (Table 1). 6 PTS (46%) had previous allografts fail due to C3G recurrence. Age at transplant was 32 years (18-71). Time from transplant to histologic recurrence was 54 days (5-472). 4 PTS (31%) had bland urine at first recurrence. 7 PTS (54%) had histologic recurrence at first allograft bx,15 days (5-56) after transplant. After 2.3 years (0.33-10.1), 11 PTS (85%) remained with functioning allografts; 5 PTS (46%) had creatinine > 2 mg/dl. 2 DDD PTS had allograft failure. 6 PTS (43%) had acute T cell mediated rejection. 2 PTS received eculizumab- both were without clinical recurrence.
Conclusion
This series highlights earlier histologic recurrence of C3G in the allograft than previously reported, partly due to protocol bx. Many PTS were without urinary abnormalities. At last follow up, majority of PTS had significant transplant CKD and 2 lost their allografts. Future study is needed to better understand if early detection of recurrence, coupled with anti-complement therapies, improves outcomes.
Summary of Clinicopathologic Course After Histologic Recurrence
| Patient ID | Transplant Type | Native Disease | Days to Histologic Recurrence | Protocol vs For Cause | Immunosuppression at Histologic Recurrence | Serum Creatinine (SCR) at Biopsy (mg/dl) | LM Findings at First Recurrence | Most Severe LM Findings on Follow Up | Most Severe Rejection on Follow Up | Allograft outcome | Eculizumab at last follow up | Follow Up Time OR Time to Allograft Failure (Years) |
| 1 | DDKT | DDD | 24 | For Cause | Tacrolimus, IVIG, Myfortic | 2.0 | Mild Mesangial Proliferative | Mild Mesangial Proliferative | 1A ACR | SCR 2.2, No hematuria, No proteinuria | Yes | 4.2 |
| 2 | LDKT | C3GN | 12 | For Cause | Tacrolimus, Myfortic, Prednisone, Eculizumab | 4.7 | Mild Mesangial Proliferative | Mild Mesangial Proliferative | 1B ACR | SCR 1.1, No hematuria, No proteinuria | Yes | 3.4 |
| 3 | LDKT | C3GN | 5 | Protocol | PLEX, Rituximab, IVIG (DSA+), Tacrolimus, Myfortic, Prednisone | 4.3 | Mild Mesangial Proliferative | Diffuse Mesangial Proliferative with Mild Endocapillary Hypercellularity | 1B ACR | SCR 2.9, Hematuria, Proteinuria | No | 3.2 |
| 4 | LDKT | DDD | 472 | Protocol | Tacrolimus, Myfortic | 1.5 | LM negative, IF/EM+ | LM negative, IF/EM+ | None | SCR 1.4, No hematuria, No proteinuria | No | 4 |
| 5 | DDKT | C3GN | 466 | For Cause | Tacrolimus, Myfortic | 3.2 | Mild Mesangial Proliferative | Mild Mesangial and Membranoproliferative, Severe Sclerosing | None | SCR 3.6, No hematuria, proteinuria | No | 9.7 |
| 6 | LDKT | C3GN | 84 | Protocol | Tacrolimus, MMF, Prednisone | 1.5 | LM negative, IF/EM+ | Mild Mesangial Proliferative | None | SCR 1.5 No hematuria No proteinuria | No | 2.1 |
| 7 | LRKT | DDD | 356 | Protocol | Tacrolimus, MMF | 1.9 | Diffuse Mesangial Proliferative & Sclerosing | Mesangial and membranoproliferative proliferative, endocapillary proliferative, cellular crescents, severe sclerosing | 2A ACR | Failed allograft, re-transplanted | No | 10.1 |
| 8 | DDKT | C3GN | 54 | For Cause | Belatacept, MMF | 1.9 | LM negative, IF/EM+ | LM negative, IF/EM+ | Chronic Active T Cell Mediated Rejection (borderline) | SCR 1.8, No hematuria, No proteinuria | No | 2 |
| 9 | DDKT | C3GN | 21 | For Cause | Tacrolimus, MMF | 4.0 | LM negative, IF/EM+ | Mild Mesangial Proliferative | None | SCR 1.5, No hematuria, No proteinuria | No | 2.3 |
| 10 | LDKT | C3GN | 8 | For Cause | Tacrolimus, MMF | 2.2 | LM negative, IF/EM+ | LM negative, IF/EM+ | None | SCR 2.1 | No | 1.1 |
| 11 | LDKT | C3GN | 120 | Protocol | N/A | 2.0 | LM negative, IF/EM+ | Mild Mesangial Proliferative | Chronic Active T Cell Mediated Rejection (2A) | SCR 2.1 | No | 1 |
| 12 | DDKT | DDD | 56 | For Cause | Tacrolimus, Myfortic | 2.1 | LM negative, IF/EM+ | Focal Necrotizing and Crescentic GN | None | Failed Allograft, on HD | No | 0.33 |
| 13 | LDKT | C3GN | 15 | For Cause | Tacrolimus, Myfortic | 1.6 | LM negative, IF+ | Mild Mesangial Proliferative | None | SCR 1.5, Hematuria, Proteinuria | No | 1 |