Introduction: C5 inhibition with eculizumab/ravulizumab is recently well-established treatment for thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS) and for C3 nephropathy, but its use in kidney transplant patients has still not been widely reported.
Method: We retrospectively analyzed the records of kidney transplant patients from the University Medical Centre Ljubljana, treated with eculizumab and/or ravulizumab, including their clinical, laboratory, and histological characteristics and outcomes.
Results: From 2018 to the end of 2023, we treated 12 patients after kidney transplantation with anticomplement therapy, 7 men, 5 women, average age 44 years. The indications were primary aHUS in one patient, secondary aHUS in 7, chronic antibody-mediated rejection (AMR) in one and C3 nephropathy in 3 patients.
In a 22-year-old woman with primary aHUS (homozygous deletion of the CFHR1 and CFHR3 genes and positive anti-factor H antibodies), eculizumab was introduced immediately prior to a deceased-donor kidney transplantation. A surveillance kidney biopsy after one year showed no signs of TMA. She is currently being treated with ravulizumab and has no laboratory signs of TMA. Serum creatinine is 130 µmol/L and anti-factor H antibodies are negative.
Seven patients were treated in the early post-transplant period. 4 of them due to de novo TMA in association with ischemia-reperfusion injury and/or calcineurin inhibitor toxicity, 3 had AMR with atypical presentation. In addition to graft dysfunction, 4 of 7 patients had laboratory signs of TMA that resolved after short-term treatment with eculizumab. Kidney function recovered in 5 of 7 patients (71%), while 2 progressed to end-stage kidney failure (one without and one with AMR). One patient had an early recurrence of TMA and is being treated chronically with ravulizumab. Genetic results were positive in 2, negative in 2, not available in 2 patients and we are still waiting for results in one patient.
One woman was successfully treated with eculizumab (in addition to other immunosuppressive therapies) 8 years after transplantation for chronic active AMR without TMA, genetic results are not available.
Two patients were diagnosed with recurrence of C3 nephropathy approximately 1 year after transplantation (genetic analysis in progress), and one patient developed de novo disease almost 2 years after transplantation (presence of homozygous risk haplotype CFH-H1). All continue to be treated with ravulizumab, with a decrease in proteinuria and serum creatinine observed in two patients.
No infections with encapsulated organisms occurred during the follow-up.
Conclusion: C5 inhibition with eculizumab and ravulizumab is effective and safe in kidney transplant patients with primary aHUS, de novo TMA (with or without AMR) and C3 nephropathy.