Yasunobu Ishikawa

Transplantation-associated thrombotic microangiopathy after steroid pulse therapy for polyserositis related to graft-versus-host disease.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a rare but devastating syndrome that occurs in allogeneic hematopoietic stem cell transplant recipients, and is associated with a variety of transplantation-related factors, including conditioning regimens, immunosuppressive agents, graft-versus-host disease (GVHD) and opportunistic infections. TA-TMA has an unfavorable prognosis and responds poorly to conventional treatment including plasma exchange (PE). We present a case of a 37-year-old man with membranous nephropathy (MN) and polyserositis caused by GVHD after hematopoietic stem cell transplantation. He developed TA-TMA after steroid pulse therapy for polyserositis. We treated the patient with PE and mycophenolate mofetil (MMF) after which the TA-TMA successfully improved and the MN underwent complete remission. The present case suggests that corticosteroids with severe GVHD might increase the risk of TA-TMA, and that PE in combination with MMF may be a valuable therapy to improve the prognosis.

A case of adefovir-induced membranous nephropathy related to hepatitis B caused by lamivudine-resistant virus after liver transplant due to Byler’s disease

We report on how adefovir-induced membranous nephropathy related to hepatitis B was caused by lamivudine-resistant virus after a liver transplant due to Byler’s disease. In 1980, a 2-year-old girl was diagnosed with Byler’s disease (familial progressive familial intrahepatic cholestasis). In 1994 (at the age of 14 years) she underwent a liver transplant with her father as the donor. In 2003, hematuria and proteinuria appeared and shortly afterwards her renal function rapidly decreased. A renal biopsy showed atypical membranous nephropathy, which suggested the possibility of a secondary renal disease. The patient had suffered from chronic hepatitis type B (HBV). In 2001 she was administered lamivudine which is an antiviral drug; it was around this time that hematuria and proteinuria appeared as well as an increase of the virus titer. We believed the HBV-related membranous nephropathy was the cause of the virus titer and the renal histology. We concluded that the patient’s condition had become resistant to lamivudine medication. Therefore, in February 2004 we administered adefovir, a new drug at the time, to treat the HBV. In April 2004, the HB virus titer decreased and the hematuria and proteinuria decreased. The patient’s renal function also showed improvement. HBV-associated nephropathy is caused by HBV antigen deposition in the glomeruli. Generally the first choice of treatment is antivirus therapy. There are many reports demonstrating that administration of interferon and lamivudine are effective; however, there are few reports that show adefovir as an effective treatment for HBV-associated nephropathy.