Intermediate‐dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy

Abstract

BK virus allograft nephropathy (BKVAN) is a rising complication in kidney transplant recipients. Reducing immunosuppression has been the initial form of therapy in most cases, but is not always associated with improvement in graft function. Anti-viral therapy with low-dose cidofovir (0.25-0.42 mg/kg/dose) has been used successfully in some patients, but dose-related nephrotoxicity has limited its use. We present our experience with 3 kidney transplant recipients diagnosed with BKVAN who received intermediate-dose cidofovir (0.75-1.0 mg/kg/dose) without probenecid, and without concomitant nephrotoxicity. Three female patients, ages 8, 19 and 20 yr, presented with elevated serum creatinine (SCr) values, BK virus stain positive on renal biopsy and high plasma BK viral loads. As a result of viral loads being >2 million copies/ml in two patients and a lack of response to reduction in immunosuppression in the third, we initiated therapy with low-dose cidofovir. Because of persistent positive BK stain and positive plasma viral load, we then administered intermediate-dose cidofovir, without probenecid, for several subsequent doses (seven to 15 infusions till date). All patients tolerated the intermediate-dose cidofovir with no significant rise in SCr during the course of the infusions. The most recent SCr values in all three patients were improved from those at the initial diagnosis of BKVAN. All three patients showed a marked drop in BK viral loads when on intermediate-dose cidofovir, with complete clearing of viremia in two patients. In our experience, intermediate-dose cidofovir without probenecid, used judiciously, is not associated with additional nephrotoxicity and may provide an additional alternative for treatment.

BK Virus Nephropathy in Pediatric Renal Transplant Recipients

“…Biopsy-proven rejection after immunosuppression reduction is reported in up to 25% of patients (29), which compares to 32% seen in the NAPRTCS cohort. Although there have been no controlled trials, antiviral therapy with cidofovir has been reported in cases in which immunosuppression reduction is not sufficient (13,14,30). In our study, cidofovir was used in six (24%) of 25 cases.…”

Polyomavirus-associated nephropathy

“…However, results evidenced a scarce, if any, significant effect in clearing viruria or viremia [75][76][77][78] . Other studies reported clearance of viremia in 50% to 100% of the cases [75,[79][80][81][82] . The effect of cidofovir on renal function was variable, with some studies evidencing stabilization of creatinine [79][80][81] and others Table 4 Recommended treatment of polyomavirus-associated nephropathy by reduction or switching of immunosuppression [49] …”

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“…The use of cidofovir, leflunomide, ciprofloxacin, and immunoglobulins remain questionable. [3][4][5][6][7][8] Our audit confirms that reducing immunosuppression appears to be the best approach for treating BKVN until a safe antiviral agent becomes available to treat this condition.…”

“…1 Although these drugs are meant to prevent or reduce the incidence of acute rejections, and prolong the survival of the transplanted graft, the harm these drugs are causing is debatable. 2,3 Much research has shown that BKVN is selflimiting in many cases; however, some cases might need strategic interventions to eliminate the virus while preserving the transplanted kidney functions. 1,2 Starting with reduction of immunosuppressive agents; which is the criterion standard-to using other agents (eg, quinolone antibiotics, intravenous immunoglobulins, and leflunomide).…”

“…[4][5][6][7][8] Additionally some centers also use cidofovir as an antiviral. 3 It is important to consider treating BKVN, as untreated BKV infections lead to graft dysfunction or loss. The challenge that faces most centers with patients having BKVN is that there is no standard antiviral agent, and all the above-mentioned agents are used off-label.…”