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Novel Treatment of ANCA Negative de novo Crescent Glomerulonephritis after Liver Transplantation using Rituxan
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Veröffentlicht: | 24. April 2015 |
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Introduction: Crescent glomerulonephritis (GN) has a poor prognosis. Cytoxan is the first line treatment in combination with steroids. We report trreatment of ANCA negative glomerulonethritis with Rituxan. While there have been sparse reports about treatment of recurrent glomerulonephritis with Rituxan, we report for the first time using this drug in ANCA negative GN. The rationale for chosing Rituxan over methotrexate was the fact that the patient had just received a liver transplantation for alcoholic cirrhosis 6 weeks prior. We felt that Cytoxan would be too unspecific and likely would result in poor outcome secondary to infectious complicatuions in our immunosuppressed patient.
Material and methods: The patient is a 62-year-old black man who had been transfered from an outside hospital with end stage liver disease secondary to alcoholic cirrhosis and a MELD of 37. While being evaluated for liver transplantation he developed hepatorenal syndrom (urine sodium <20 mmol/l) requiring dialysis (mostly CVVH). His base line creatinine just a few weeks prior to transfer had been 1.5 mg/dl. Three weeks after listing he received a compatible donor graft. The procedure went well, immunosuppression consisted of mycophenolate mofetil, Simulect and several days of steroids. Tacrolimus was started later in order to give the kidneys a chance to recover. Four weeks after transplantation his renal function recovered and he came off dialysis (creatinine down to 1.3 mg/dl). Just seven days later, however, his urine output decreased and his creatinine increased. He was yet again requiring dialysis and the biopsy revealed crescent glomerulonephritis. 26/31 glomeruli had glomerulonephritis, and 7/26 showed crescents and necrosis. 30% of arterioles were sclerosed. Steroid pulses (1 gram solumedrol x three days) did not improve urine output nor creatinine. 7 days after reinitiation of dialysis we decided to give Rituxan (325 mg/m2 x 2 doses, 10 days apart).
Results: Within 24 hours the urine output increased, and the last dialysis was 5 days after the first Rituxan infusion. He has now been stable for 4 months, there has not been the need for repeat biopsy. However, his baseline creatinine is elevated at 1.9 mg/dl. We are aiming for a tacrolimus trough level of 4 ng/ml or less. The plan is is to repeat a renal biopsy to assess for ongoing glomerulonephritis.
Conclusion: The administration of Rituxan in ANCA negative glomerulonephritis prooved to be safe and effective. This patient had a poor prognosis in terms of maintaining his renal function as well as quoad vitam. Rituxan showed to be effective even in ANCA negative GN. It remains to be seen if and in what intervals further doses might be required to maintain this good outcome.