ABSTRACT
BACKGROUND: The introduction of combination therapy with glucocorticoids (GC) and cyclophosphamide (CYC) or rituximab (RTX) has resulted in remission rates exceeding 90% in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, early treatment-related mortality remains a major concern and has driven the search for safer induction regimens exploring minimization or avoidance of GC and CYC. Most trials have excluded patients with severe renal disease. We report the outcomes of AAV patients with severe renal disease treated with sequential therapy (ST) starting with (GC) and oral (CYC) followed by transition to (RTX). METHODS: Patients with new or relapsing severe AAV who presented with severe renal disease and/or rapidly progressive glomerulonephritis (RPGN) were identified. RPGN was defined as at least a 20% decrease in estimated glomerular filtration rate (eGFR) over a 2-week period along with hematuria and proteinuria. Induction treatment included pulse (GC) for 3 days followed by oral prednisone tapered to 5 mg by month 6, oral (CYC) adjusted for GFR until improvement in Birmingham Vasculitis Activity Score (BVAS), and serum creatinine at which point (CYC) was stopped and induction dose of (RTX) was given. Use of plasmapheresis (PLEX) was allowed. The primary outcome was complete remission defined as BVAS of zero by 6 months. Descriptive data are presented as median with range and mean with SD. RESULTS: Nine patients met the inclusion criteria. Median age at diagnosis was 63 years. The majority were females, myeloperoxidase ANCA positive, and had a new diagnosis. The mean nadir (SD) eGFR was 12 (5) with 3 requiring dialysis. The median BVAS at the time of diagnosis was 15. All patients received ST and 3 received PLEX. The median exposure to oral CYC was 35 days. The mean (SD) eGFR and median BVAS were 26 (12) and 3, respectively, at the time of switching to RTX. The median prednisone dose at 6M was 5 mg. The median follow-up was 44 months. All patients achieved remission. One patient with relapsing disease reached ESRD. The mean (SD) eGFR in the remaining 8 patients at last FU was 37 (27), and the mean (SD) eGFR rise at 1 year was 26 (25). Adverse events included 2 patients with pneumonia and 3 with bone marrow suppression. There were no deaths. CONCLUSION: ST with GC and CYC followed by RTX is effective for in AAV patients with severe renal disease. Therapy-related adverse events are comparable to other studies, and further modification in ST with decrease in GC dosage should be explored.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Glomerulonephritis/drug therapy , Immunosuppressive Agents/administration & dosage , Remission Induction/methods , Adult , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Female , Glomerular Filtration Rate/drug effects , Glomerular Filtration Rate/immunology , Glomerulonephritis/diagnosis , Glomerulonephritis/immunology , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Rituximab/administration & dosage , Rituximab/adverse effects , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: Pediatric en bloc kidneys are considered marginal for transplantation into adults. We aimed to compare the long-term outcomes of pediatric en bloc versus living donor kidney transplantation. METHODS: A retrospective review was undertaken on pediatric en bloc and living donor kidney transplants performed at our center between 1990 and 2001. The outcomes compared between the groups included 25 year graft survival and longitudinal glomerular filtration rate. RESULTS: There were 72 pediatric en bloc and 75 living donor kidney recipients included in the analysis. Pediatric donors were 16.9 ± 11.2 months old and weighed 10.7 ± 3.8 kg with terminal serum creatinine of 0.50 ± 0.45 mg/dL. Living donors were 40.1 ± 9.4 years old and serum creatinine was 0.90 ± 0.16 mg/dL at the time of donation. En bloc kidney recipients had higher dialysis vintage (23.0 ± 29.2 months vs 14.3 ± 14.7 months; P = 0.03), and longer cold ischemia time (30.5 ± 9.8 hours vs 2.6 ± 0.9 hours, P < 0.001). Kaplan-Meier estimate revealed similar graft survival between the groups up to 27 years of follow up (log rank P = 0.78). Estimated glomerular filtration rate was significantly higher in pediatric en bloc kidney recipients from years 5 through 17 posttransplantation. CONCLUSIONS: Pediatric en bloc kidneys conferred long-term graft survival similar to living donor kidneys over a 25-year period after transplantation along with superior graft function. These findings support improved utilization of pediatric kidneys for transplantation into adults which not only helps to alleviate organ shortage but also provide excellent long-term function.