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Walter Atwood

Publications and source records attributed to Walter Atwood.

3 recordsLinked to original sources
PubMed2006

Treatment of renal allograft polyoma BK virus infection with leflunomide.

BACKGROUND: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals. METHODS: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy. RESULTS: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added. CONCLUSIONS: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

Aniline Compounds↗
PubMed2004

Basic and clinical research in polyomavirus nephropathy.

Over the last decade, polyomavirus nephropathy (PVN) has emerged as an important cause of renal allograft dysfunction and graft loss. PVN occurs with a prevalence of 1%-8% in renal transplant recipients and is most commonly reported within the first 12 months posttransplant. The human polyomavirus, BK virus, is thought to be the primary etiologic agent of PVN. Risk factors for PVN are not well defined and are most likely a result of a complex interaction between multiple donor and recipient factors. Definitive diagnosis of PVN is made through histological assessment of a renal allograft biopsy. Recent studies have also evaluated noninvasive urine and serum markers for screening of BK virus replication and as adjunct tools in PVN diagnosis and monitoring. The principal treatment for PVN is immunosuppression reduction, but this must be balanced against the risks of rejection. If rejection occurs concurrently with PVN, a brief increase in immunosuppression to treat the rejection episode followed by a subsequent reduction in immunosuppression is recommended. No antiviral treatments for PVN have been approved by the Food and Drug Administration. Although the antiviral drug cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Small series of patients treated with leflunomide and intravenous immune globulin therapy for PVN have also recently been reported. Retransplantation after graft loss due to PVN is feasible, but experience is limited. Current research is focusing on identifying PVN risk factors, refining screening, diagnostic and monitoring methods, and developing therapy for prophylaxis and treatment of PVN with the goals of decreasing the prevalence of PVN and improving allograft outcomes in renal transplant recipients diagnosed with PVN. This review will present recent advances in basic and clinical research related to PVN and renal transplantation.

Humans↗