The treatment for chronic active antibody-mediated rejection (CAMR) remains controversial. We investigated the efficacy of rituximab (RTX) and intravenous immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m2) and IVIg (0.4 g/kg) for 4 days. The efficacy of RTX/IVIg combination therapy (RIT) was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR) before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18), and overall ΔeGFR decreased significantly to 0.4 ± 1.7 mL·min−1
·1.73 m−2 per month 6 months after RIT compared to that observed 6 months before RIT (1.8 ± 1.0, P < 0.05). Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5 ± 2.5 versus 7.0 ± 3.5 protein/creatinine (g/g), P < 0.001). The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT.
BackgroundNephrotic syndrome (NS) and proteinuria are uncommon, often unrecognized manifestations of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Only a few isolated case reports and case series involving smaller number of patients who developed NS after HSCT have been published.MethodsWe reviewed the renal histopathological examination findings and clinical records of 15 patients who developed proteinuria after HSCT at Seoul and Yeouido St. Mary′s Hospital (Seoul, Korea). We also measured the anti-PLA2R antibodies (M-type phospholipase A2 receptor) in the serum samples from the seven patients at the time of renal biopsy.ResultsAll patients had GVHD. The most common indication for biopsy was proteinuria (>1 g/day), with nine patients having nephrotic range proteinuria. The most common histopathological finding was membranous nephropathy (MN; n = 12). Other findings were membranoproliferative glomerulonephritis, C1q nephropathy, and diabetic nephropathy. Eleven patients were treated with immunosuppressive agents, and three patients were treated only with angiotensin II receptor blocker. The overall response rate, including complete remission (urinary protein level <0.3 g/day) and partial remission (urinary protein level = 0.31–3.4 g/day), was 73%. The mean follow-up period was 26 months, and none of the patients developed end-stage renal disease. All of the seven patients with MN had negative findings for anti-PLA2R antibodies, measured using an enzyme-linked immunosorbent assay kit.ConclusionIn this study the findings of 15 renal biopsies were analyzed and to our knowledge this is the largest clinicopathological study of GVHD-related biopsy-proven nephropathy. Approximately 80% of the patients were MN and 73% responded either partially or completely to immunosuppressive treatment. Currently, there is an increase in the incidence of GVHD-mediated renal disease, and therefore, renal biopsy is essential for diagnosing the nephropathy and preventing the progression of renal disease.
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