Effect of mTOR inhibitors during CMV disease in kidney transplant recipients: Results of a pilot retrospective study

Abstract

AbstractmTOR inhibitors exert a preventive effect on cytomegalovirus (CMV) disease in CMV seropositive (R+) kidney transplant recipients, but their impact during the curative treatment of CMV disease in high‐risk kidney transplant recipients has not been investigated. We aimed to evaluate the efficacy and tolerance of mTOR inhibitors compared with mycophenolic acid in 63 consecutive kidney transplant recipients (80% of D+R−) suffering from CMV disease with a persistent or a recurrent CMV DNAemia. In this monocentric retrospective study, 16 had their treatment converted to mTOR inhibitors and 47 did not. The Kaplan–Meier curves did not show any significant differences in CMV DNAemia eradication (77% vs. 88% respectively; hazard ratio (HR), 1.648 [95% confidence interval (CI), 0.913–2.973]; log‐rank test, P = .132), DNAemia recurrence (36% vs. 47%; HR, 1.517 [95% CI, 0.574–4.007]; log‐rank test, P = .448) and CMV clinical recurrence (17% vs. 27%; HR, 1.375 [95% CI, 0.340–5.552]; log‐rank test, P = .677) between patients who received mTOR inhibitors and those who did not. These results were confirmed in uni‐ and multivariate time‐dependent Cox regressions. In summary, conversion from mycophenolic acid to mTOR inhibitors seems inadequate for improving CMV clearance or in better preventing CMV recurrences during severe or persistent CMV disease.

Case Report: Management of a Multidrug-Resistant CMV-Strain in a Renal Transplant Recipient by High-Dose CMV-Specific Immunoglobulins, Modulation in Immunosuppression, and Induction of CMV-Specific Cellular Immunity

“…This case report shows that high-dose CMV-IVIG may represent a valuable alternative in patients with multidrug-resistant strains, which has shown efficacy as adjunct therapy of CMV infections ( 10 ). In addition, although mTOR inhibitors may be more effective in CMV prevention than control ( 11 , 12 ), early conversion of immunosuppressive drugs to a regimen containing an mTOR inhibitor may have at least in part contributed to viral control in our patient ( 11 , 13 ). This may be related to its direct antiviral activity ( 4 ).…”

The incidence of cytomegalovirus and BK polyomavirus infections in kidney transplant patients receiving mTOR inhibitors: A systematic review and meta‐analysis

“…But another study showed that switching to mTORI seemed inadequate for improving CMV clearance or preventing CMV recurrences. 4 When converting from mycophenolate mofetil (MMF) to EVR, a trend was demonstrated toward improved viral clearance, but did not reach statistical significance, in BKPyV infection. 5 A trial evaluating switching RTxRs from TAC/MMF to either EVR with reduced calcineurin inhibitor (CNI) or MMF with reduced CNI to treat BK polyomavirus infection resulted in no difference between the combination therapy and MMF with reduced CNI in the combined end point of resolution of BK viremia or 50% reduction in viruria.…”

“…In particular, the incidence of CMV and BKPyV infections was lower in the EVR group compared with the MPA group (CMV: 3.6% versus 13.3%, p < 0.001; BKPyV: 4.3% versus 8.0%, p < 0.001, respectively). But another study showed that switching to mTORI seemed inadequate for improving CMV clearance or preventing CMV recurrences 4 . When converting from mycophenolate mofetil (MMF) to EVR, a trend was demonstrated toward improved viral clearance, but did not reach statistical significance, in BKPyV infection 5 .…”