RESUMEN
A 75-year-old woman, with hypertension and atrial fibrillation but no prior renal history, presented to the hospital for chest discomfort and dyspnea. She was found to be in acute renal failure, with a serum creatinine of 5.1, increased from a baseline of 0.9, and urine analysis revealing proteinuria and hematuria with dysmorphic red blood cells. Subsequent work up was significant for positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and myeloperoxidase antibodies. She underwent a renal biopsy, which revealed necrotizing crescents in 12 of 14 glomeruli, and she was diagnosed with rapidly progressive glomerulonephritis due to microscopic polyangiitis. Despite aggressive treatment with plasmapheresis, high-dose prednisone, and rituximab infusions, renal function worsened, and she required initiation of hemodialysis. She was ultimately discharged after a three-week admission, with plans to continue rituximab infusions and three times weekly hemodialysis in the outpatient setting. Due to her poor response to traditional therapies, initiation of a new targeted immunomodulator known as avacopan, a complement 5a receptor antagonist, was considered. Such targeted immunomodulators are also of particular interest as possible ways to reduce the risk of severe infection associated with current broad immunosuppressive modalities. In addition, when used in place of steroids, they reduce the morbidity associated with cumulative glucocorticoid toxicity. For patients with ANCA-associated vasculitis refractory to standard therapies, targeted immunomodulators such as avacopan should be considered as alternative or adjunct therapy.
RESUMEN
BACKGROUND: Despite ubiquitous exposure to sensitizing events, most Fontan PLE patients have low panel reactive antibodies (PRA). To assess whether they are at risk for donor-specific antibody (DSA) memory response following heart transplantation (HT) when their PLE resolves, DSA profiles, incidence of rejection, and graft outcomes in Fontan recipients with and without PLE were compared. METHODS: Patient characteristics, appearance of newly detected DSA (nDSA), and graft outcomes were compared between patients with and without PLE using Wilcoxon rank-sum and Chi-squared tests. DSA burden was quantified using titers and time to nDSA, incidence of rejection, and graft outcomes were compared using Kaplan-Meier curves and the log-rank test. RESULTS: Characteristics of patients with and without PLE were similar. Lymphocyte and albumin levels were lower in the PLE group, and flow PRA were comparable. Graft failure, CAV, and ACR were similar between the two groups, but AMR occurred more frequently in the PLE group (p = .03). Nearly 50% of PLE patients experienced class II nDSA by 1-year post-HT, compared to 30% of non-PLE patients, but this difference was statistically not significant. Antibody burden did not differ between groups. CONCLUSIONS: In this cohort, PLE was associated with AMR within the first-year post-HT, despite no significant difference in nDSA. Small patient numbers limited statistical comparison of nDSA in this cohort. PLE may be a risk factor for AMR post-HT, and the possibility of a clinically important DSA memory response remains. Larger studies are necessary to better understand these preliminary findings.