The therapeutic effect of switching from tacrolimus to low-dose cyclosporine A in renal transplant recipients with BK virus nephropathy

Abstract

Background: There is no effective therapy for BK virus (BKV) nephropathy (BKVN). Cyclosporine A (CsA) has a lower immunosuppressive effect than tacrolimus. In vitro studies have shown that CsA inhibits BKV replication. The present study aimed to evaluate the effectiveness of switching from tacrolimus to low-dose CsA in renal transplant recipients with BKVN. Methods: Twenty-four patients diagnosed with BKVN between January 2015 and December 2016 were included. Tacrolimus was switched to low-dose CsA, and patients were followed for 24 months. Primary end points were BKV clearance in blood and graft. Secondary end points were urine specific gravity, serum creatinine, and graft loss. Results: The viremia in all patients cleared at a mean of 2.7 ± 2.0 months after switching to CsA. Urine specific gravity at 3 months after switching to CsA increased significantly compared with that at diagnosis (P=0.002). The timing and trend of urine specific gravity increase was consistent with the timing and trend of blood and urine viral load decrease. Repeated biopsies at a median of 11.2 months (range: 9.1–12.5 months) after switching to CsA showed that 8 patients (42.1%) were negative for BKV, and 11 patients (58.9%) had a decrease in BKV load (P<0.001). There was no statistical difference in the serum creatinine level between the time of diagnosis and 24 months of CsA therapy (P=0.963). The graft survival rate was 100%. Only two patients (8.3%) suffered from acute rejection. Conclusion: Switching from tacrolimus to low-dose CsA may be an effective therapy for BKVN.

<p>Clinical Efficacy of Intravenous Immunoglobulin for BK Polyomavirus-Associated Nephropathy After Living Kidney Transplantation</p>

“…5,10 For a certain number of patients, conversion of TAC to lowdosage CsA is effective to lower the severity of BKPyVAN since the immunosuppressive strength of CsA is weaker than that of TAC. 11 Anti-viral drugs, leflunomide or cidofovir had a certain effect on BKPyVAN. 12 However, it is difficult to use these drugs since these are nephrotoxic for patients with unstable renal function and have low selectivity for BKPyV.…”

Diagnostic utility of urine cytology in detection of decoy cells in renal transplant patients: Report of five cases and review of literature

“…Currently, the estimated incidence is 10% of transplant recipients have BK virus nephropathy (BKVN) with 50% result in graft loss of those affected. 12,13 The diagnosis may be complicated with the coexistence of acute rejection since overlapping histological findings may hinder any differentiation between the two processes. This also turns out to be a double-edged sword in a complex clinical condition, since treating one will aggravate the clinical course of the other.…”

“…Urine with large numbers of decoy cells (>10 cells/cytospin), inflammatory sediments, and biopsy proven PVN have been noted to have significantly greater deterioration of renal function than patients with no evidence of PVN. 1,13,19 Decoy cells should not be mistaken for malignant cells. The former are medium-sized basophilic cells with comet tail cytoplasm and nuclei with ground glass chromatin, while the later have unevenly distributed hyperchromatic chromatin with irregular nuclear membrane and little cytoplasm.…”

“…Other than PV BK strain in decoy cells, there can be JC strain and adeno virus also 5. Currently, the estimated incidence is 10% of transplant recipients have BK virus nephropathy (BKVN) with 50%result in graft loss of those affected 12,13. Patient with suppressed immunity, pregnant women (3%), patients with malignancies (13%), diabetics (3%), renal allograft recipients without any dysfunction (23%) and cardiacF I G U R E 3 Cytospin smear showing intranuclear inclusion with irregular halo (arrow-"cytomegalovirus (CMV)" like type II inclusion).…”

<p>BK Virus Nephropathy: Prevalence, Impact and Management Strategies</p>

“…Switching to Cyclosporine A (CsA) has been shown to have some benefit as well. 45 Switching from Tacrolimus to CsA is a common approach used in our center in patients with persistent viremia; However, a higher incidence of biopsy-proven acute rejection is seen with this approach. 46 Failure of reduction in viral load should prompt reduction of mycophenolate mofetil (MMF) by 50%, or discontinuation of MMF or switching to an mTOR inhibitor.…”