Successful treatment with foscarnet for ganciclovir‐resistant cytomegalovirus infection in a kidney transplant recipient: A case report

Abstract

ABSTRACT:Cytomegalovirus (CMV) infection is the most common infectious complication following solid organ transplantation. Ganciclovir (GCV)-resistant CMV infection may be fatal, and is difficult to treat while avoiding allograft rejection. A 31-year-old woman received a second ABO-incompatible kidney transplant, from her father. Induction therapy consisted of basiliximab and rituximab followed by maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and methylprednisolone. Her CMV serostatus was D + /R -at second transplant and she received prophylactic low-dose valganciclovir (VGCV). BK polyoma virus nephropathy (BKVN) developed 7 months after transplant concurrent with CMV hepatitis and retinitis. VGCV was increased to a therapeutic dose combined with reduced immunosuppression with minimal methylprednisolone (2 mg/day) and everolimus (0.5 mg/day). However, pp65 antigenaemia continued to increase for 6 weeks. Her CMV was defined as ganciclovir (GCV)-resistant. Foscarnet was therefore administered and her CMV disease resolved within 2 weeks. Kidney allograft dysfunction developed 9 months after transplant, and graft biopsy showed tubulointerstitial injury with crystal deposition suggesting foscarnet nephrotoxicity, with no findings of BKVN or rejection. Kidney function recovered after cessation of foscarnet and the patient had good graft function 18 months after transplant. This case demonstrates the successful use of foscarnet to treat GCV-resistant CMV infection after ABO-incompatible kidney transplant complicated with BKVN, without acute allograft rejection. This case further highlights the need to establish appropriate management for CMV D + /R -patients to avoid the acquisition of GCV-resistant gene mutations.

Brincidofovir Use after Foscarnet Crystal Nephropathy in a Kidney Transplant Recipient with Multiresistant Cytomegalovirus Infection

“…FOS nephropathy does not seem to appear during the first days of therapy but rather after several weeks of treatment. Glomerular crystallization seems to be associated with worse acute kidney injury than isolated tubular crystallization [12]. At worst, FOS nephropathy led to kidney graft loss.…”

Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review

“…It is a CD20‐specific monoclonal antibody which depletes peripheral blood B cells and can also cause prolonged hypogammaglobuinaemia, predisposing to infections . All reported cases of necrotising retinitis in patients who were on rituximab had complicating factors such as concurrent other intensive immunosuppression and corticosteroid therapy . Most cases were of CMV retinitis, with one case each of ARN and PORN .…”

“…Systemic immunosuppression should be addressed in consultation with the patient's treating teams. The precipitating drug/s may be able to be discontinued, the intensity of immunosuppression decreased or an alternative therapy considered . Ongoing, possibly lifelong, reviews are necessary and patients should be made aware of the need for prompt ophthalmic evaluation with new symptomatology.…”

“…148 All reported cases of necrotising retinitis in patients who were on rituximab had complicating factors such as concurrent other intensive immunosuppression and corticosteroid therapy. 91,[163][164][165][166][167][168][169] Most cases were of CMV retinitis, [163][164][165][166]168 with one case each of ARN 169 and PORN. 91 Lymphopenia was a common feature and all patients were HIV-negative.…”

“…Anti-T-cell biologics such as anti-thymocyte globulin (ATG, Thymoglobulin ® ) and basiliximab (Simulect ® ) have been associated with CMV retinitis. 41,168,[170][171][172] Alemtuzumab (Campath ® , Lemtrada) is a recombinant DNA-derived humanised monoclonal antibody against CD52, an antigen present on both B and T lymphocytes in addition to other immune cells. 173 Iatrogenic immunosuppression is thought to be secondary to depletion of CD4+ and CD8+ T-lymphocytes.…”