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.

BK virus-associated nephropathy (BKVN) has become recognized as an important cause of allograft dysfunction in renal transplant recipients and despite reduction in immunosuppression, 30-40% of recipients ultimately progress to allograft loss. Cidofovir is an antiviral agent that demonstrates in vitro activity against murine polyomavirus and has been proposed for treatment of BKVN in renal allograft recipients. We describe the clinical course, renal function, serial renal histology and urine and blood viral load measurements in two consecutive patients with refractory BKVN who were treated with low-dose cidofovir (0.25 mg/kg IV). In each case, renal dysfunction and BK viral load progressed despite reduced immunosuppression, and persistent BK virus infection was documented in serial renal allograft biopsy specimens. Administration of lowdose cidofovir was associated with clearance of BK virus DNA from blood and allograft, and stabilization of renal function in both patients, without significant toxicity. These preliminary data suggest that low-dose cidofovir may be tolerated, even among renal transplant recipients with significant renal dysfunction due to BKVN. Prospective, controlled trials are warranted to further define the optimal dose, toxicity and potential role of cidofovir in renal transplant recipients with BK virus nephropathy.

Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.

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SummaryBackground and objectives This study characterizes the pathologic and clinical relationships of thrombotic microangiopathy (TMA) to antibody-mediated rejection (AMR) in renal allograft biopsies.Design, setting, participants, & measurements Consecutive renal allograft biopsies, routinely stained for C4d over a period of 51 months (n ϭ 1101), were reviewed. For comparative analysis of histology and clinical features, additional patients with TMA and peritubular capillary (PTC) C4d (n ϭ 5) were combined with those identified in the 51-month period of review (n ϭ 6).Results One hundred eighty-two of 1073 adequate biopsies from 563 allografts had PTC C4d in the study period. Six of 37 biopsies with TMA had PTC C4d (five at Յ90 days and one at 213 days). Early (Յ90 days) C4dϩ biopsies (n ϭ 5) had more frequent TMA (11.9% C4dϩ versus 3.4% C4dϪ; odds ratio, 3.84; P ϭ 0.03). Graft loss was significantly greater in an early C4dϩTMAϩ group (n ϭ 5 study ϩ 2 archival patients) than in C4dϩ controls without TMA (n ϭ 21) (57% versus 9.5%; P ϭ 0.02). Early TMAϩC4dϩ biopsies had more severe glomerulopathy and less severe arteriolopathy than TMAϩC4dϪ and had more frequent neutrophilic capillaritis than TMAϪC4dϩ biopsies.Conclusions TMA was infrequent in this series of unselected, consecutive, renal allograft biopsies (3.4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. TMA in allografts with suspected AMR may portend a higher risk of graft loss.