a pilot study of low-dose fludarabine in membranous nephropathy refractory to therapy.

NLM AIDSLINE A pilot study of low-dose fludarabine in membranous nephropathy refractory to therapy. Boumpas DT; Tassiulas IO; Fleisher TA; Vaughan E; Piscitelli S; Kim Y;
December 30, 1999

Clin Nephrol. 1999 Aug;52(2):67-75. Unique Identifier : AIDSLINE BACKGROUND: Lymphocytes are believed to play a role in the induction and perpetuation of membranous nephropathy. Fludarabine is a purine nucleoside analog with selective activity against both dividing and resting lymphocytes. We evaluated the tolerance, toxicity, pharmacokinetics, immunologic, and clinical effects of fludarabine in patients with membranous nephropathy in an single arm pilot study. PATIENTS AND METHODS: Eight patients with idiopathic (n = 7) or lupus (n = 1) membranous nephropathy who had failed high-dose prednisone (n = 8) and/or alkylating agents (n = 2), or cyclosporine (n = 1) were treated with 6-monthly cycles of fludarabine (cycles 1-2, 20 mg/m2/day x 2 days, cycles 3-6, 20 mg/m2/day x 3 days). Mean proteinuria was 9 g/day with a mean duration of disease of 25 months (range 12-48). Proteinuria, GFR and effective renal plasma flow were compared before and after completing the treatment. RESULTS: Seven patients completed the protocol. CD3, CD4, CD8 and B cell counts decreased by 53%, 46%, 61% and 84%, respectively, at the end of treatment and remained at lower than pretreatment levels 6 months after completing the trial. Despite lymphopenia, serum immunoglobulin levels remained unchanged. Both naive (CD45RA+) and memory CD4+ T cells (CD45RO+) were reduced (naive > memory). Proteinuria decreased by > or = 50% in 5 out of 7 patients (p = 0.11). Filtration fraction improved in all patients with decreased filtration fraction at baseline. The only side-effect observed was one episode of acute bacterial sinusitis that responded promptly to antibiotic therapy. CONCLUSION: We conclude that low-dose fludarabine treatment in patients with membranous nephropathy is well tolerated and results in significant lymphopenia involving B more than T cells. In this pilot study improvement in proteinuria and filtration rate were observed. Additional studies are required to determine the optimal dose and clinical efficacy of fludarabine. JOURNAL ARTICLE Adult Alkylating Agents/THERAPEUTIC USE Anti-Inflammatory Agents, Steroidal/THERAPEUTIC USE B-Lymphocytes/DRUG EFFECTS Comparative Study Cyclosporine/THERAPEUTIC USE CD4-Positive T-Lymphocytes/DRUG EFFECTS CD8-Positive T-Lymphocytes/DRUG EFFECTS Drug Administration Schedule Female Follow-Up Studies Glomerular Filtration Rate/DRUG EFFECTS Glomerulonephritis, Membranous/DRUG THERAPY/IMMUNOLOGY Human IgG/BLOOD Immunologic Memory/DRUG EFFECTS Immunosuppressive Agents/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/ PHARMACOKINETICS/THERAPEUTIC USE Lupus Nephritis Lymphocyte Count/DRUG EFFECTS Lymphocytes/DRUG EFFECTS Male Middle Age Pilot Projects Prednisone/THERAPEUTIC USE Proteinuria/DRUG THERAPY/URINE Renal Plasma Flow, Effective/DRUG EFFECTS Sinusitis/MICROBIOLOGY Vidarabine/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/PHARMACOKINETICS/THERAPEUTIC USE

Most Read: Latest Added Related Topics White House LGBT Conference on HIV/AIDS UNITED STATES: White House in Atlanta: LGBT AIDS Conference No more single-theme conferences: global HIV prevention conference planned FHI 360 Senior Scientist Lut Van Damme Receives International Microbicide Conference Lifetime Achievement Award Equatorial Guinea Ministry of Health and Social Welfare and UNICEF Refute Erroneous AIDS Prevalence Figures Photographs from A Day with HIV Now Online Bulgaria urges Libya to investigate AIDS nurses case Engineers enter fight against AIDS in Africa Gilead’s Complera® Non-Inferior to Atripla® Among Treatment-Naive HIV Patients UN chief Ban calls world leaders to end Aids by 2020 Positive living Lawyer: NY man at center of HIV scare not positive Zimbabwe activist: Prisoners denied AIDS drugs Youth organizations form a pact for social transformation in the AIDS response CountyCare Offers Historic Opportunity to Improve Care for People with HIV International AIDS Advocates Demand China Give $1 Billion to Global Fund Kingdom of Bahrain and UNAIDS commit to intensify cooperation CANADA: Celibate Homosexual Men Now Allowed to Donate Blood in Canada AFRICA: UN: AIDS Deaths Down, Treatment Up in Africa MICHIGAN: STD Fee for Jackson County Walk-In Clinic Takes Effect June 3 Study Finds Vitamin C Can Kill Drug-Resistant TB CONNECTICUT: Yale Researchers Urge More Street Work When Studying People With Both HIV, Hepatitis C NEVADA: Clinics Offer Low-Cost Care for those Lacking Insurance UNITED STATES: Triple Therapy for Hepatitis C is Effective After Liver Transplantation, but Side-Effects Are Common KENTUCKY: Northern Kentucky Health Department Ready to Give Low-Cost Hepatitis B Vaccines to Adults Researchers from Albert Einstein College of Medicine Report Details of New Studies and Findings in the Area of HIV/AIDS NanoPass Technologies Supports a CDC-Sponsored Phase 3 Study of Polio Vaccine in Infants as Part of its Global Health Initiative House strikes down pilot drug needle exchange Uganda: Breastfeeding Lowers HIV Transmission - Study Study Results from Eunice Kennedy Shriver National Institute of Child Health and Human Development Provide New Insights into HIV/AIDS
Information in this article was accurate in December 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.