Second Chances in C3 Glomerulopathy: Successful Kidney Retransplantation in Dense Deposit Disease

Dense Deposit Disease (DDD), a prototypical C3 glomerulopathy, represents a rare complement-mediated renal disorder characterized by dysregulation of the alternative pathway. It frequently recurs following kidney transplantation and is associated with premature allograft loss. Current therapeutic options remain limited, rendering retransplantation in such patients a formidable clinical challenge.

We present the case of a 29-year-old male who, in 2011, developed nephrotic syndrome. Renal biopsy established the diagnosis of dense deposit disease (DDD). He was subsequently managed with cyclophosphamide in combination with high-dose methylprednisolone pulse therapy. Despite these interventions, renal function steadily declined, culminating in the initiation of maintenance hemodialysis.

In 2013, the patient underwent a living-related kidney transplantation from his mother under standard triple immunosuppression. Pre-transplant genetic testing revealed no abnormalities in the Factor H, Factor I, or MCP genes, and the C3NeF test was negative. Complement analysis demonstrated normal Factor H and Factor I function, with no anti–Factor H antibodies or C3 convertase–stabilizing activity detected.

Within the first post-transplant year, recurrent DDD was histologically confirmed, prompting initiation of rituximab therapy at six-month intervals. By 2016, graft function had deteriorated irreversibly, with biopsy revealing recurrent DDD, polyomavirus-associated nephropathy, and extensive tubular atrophy, necessitating a return to dialysis.

In 2021, the patient was diagnosed with acute hepatitis B virus infection and commenced on Vemlidy (tenofovir alafenamide) 25 mg administered after each hemodialysis session. Antiviral therapy achieved HBsAg seroconversion, allowing treatment discontinuation in 2022.

Flow cytometric crossmatch demonstrated strong class I positivity (captured bead 1, HLA I 92.4%), while class II reactivity (captured beads 2 and 3, HLA IIa and IIb) remained negative. Ongoing immune activity identified through laboratory assessment prompted graft nephrectomy in 2022. In 2023, a virtual crossmatch was performed in preparation for a proposed living-donor kidney transplantation. The crossmatch result was negative, although a weak class I donor-specific antibody (B49, MFI 847) was detected.

Following multidisciplinary evaluation, a retransplantation strategy was formulated, incorporating preoperative rituximab and induction with antithymocyte globulin (ATG) due to the patient’s sensitized status and prior graft loss, aiming to reduce the risk of early rejection. Standard triple immunosuppression was initiated, targeting tacrolimus trough levels of 8–9 ng/mL. In February 2024, he received a second living-donor kidney transplant, which proceeded uneventfully. Post-transplant follow-up was notable for transient BK viremia, effectively controlled by judicious immunosuppression minimization. Surveillance biopsies demonstrated only mild, reversible tubulointerstitial injury with negative staining for polyomavirus and C4d, and without histological evidence of DDD recurrence. Renal function remains stable, with a baseline creatinine of 96 µmol/L.

Dense deposit disease (DDD) is associated with a high incidence of post-transplant recurrence, often leading to graft failure. Comprehensive pre-transplant evaluation should include detailed complement profiling and genetic testing to assess recurrence risk. In this case, careful pre-emptive immunomodulation, combined with rigorous virological surveillance and protocol-based biopsies, enabled early detection and effective management of complications. This outcome demonstrates that, even in the setting of prior graft loss and complex comorbidities, successful retransplantation can be achieved through an individualized and multidisciplinary approach.

Kidney retransplantation in patients with dense deposit disease (DDD) remains high risk but can achieve favorable outcomes when guided by individualized immunosuppressive strategies, vigilant infection monitoring, and meticulous post-transplant follow-up. This case highlights the feasibility of successful retransplantation in C3 glomerulopathies when managed within a structured and multidisciplinary clinical framework.