Chronic kidney disease (CKD) is a major health condition affecting 10% of the global population. It is characterized by a gradual loss of kidney function over time, which can ultimately lead to kidney failure, requiring dialysis or kidney transplantation to sustain life. Despite the beneficial effects of organ transplantation and improved survival rates, kidney transplant recipients are at high risk of developing opportunistic infections, which, in turn, are associated with an increased risk of acute rejection episodes, decreased graft survival, a higher incidence of chronic allograft nephropathy, and decreased patient survival.
Cytomegalovirus (CMV) is defined as the isolation of the virus or the detection of viral proteins (antigens) or nucleic acids in any body fluid or tissue sample. CMV is a common virus, with manifestations ranging from asymptomatic to severe organ dysfunction in immunocompromised patients and congenital CMV infection. Patients who have undergone hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOLT) are at higher risk of CMV infection. Among patients who have undergone pancreas or kidney-pancreas transplantation, the incidence of CMV infection is approximately 50%.
Over the past two decades, significant advances have been made in the diagnosis and treatment of CMV in organ transplant patients, enabling the development of new diagnostic methods for detecting the virus and promising clinical trials evaluating the efficacy and safety of new antiviral drugs. The prognosis for most patients with CMV is favorable unless they are immunosuppressed. Alas, patients with comorbidities and immunosuppression, which weaken the immune system, have a poor prognosis, as immunosuppressive therapy is a common cause of CMV reactivation.
In this retrospective study we aimed to determine the incidence of CMV infection in renal transplant recipients in the era of IS, to determine the incidence of CMV recurrence in renal transplant recipients, and to identify potentially modifiable predictors (risks) of CMV infection in the affected population. The data was retrospectively collected from London Health Sciences Center (LHSC). This study included data from 233 patients who underwent kidney transplantation, with a mean age of 46.7 years. Of the included data, 73% received transplants from deceased donors, and 27% from living donors. In more than a third (34.1%) of all patients, the underlying cause of end-stage renal disease (ESRD) was diabetic nephropathy (DN), followed by glomerulonephritis (19%), and hypertension (7%). Reflux nephropathy, obstructive nephropathy, tubulointerstitial disease, and hereditary kidney disease were evenly distributed among the remaining 40%.
As part of triple immunosuppressive therapy, almost all patients received mycophenolate mofetil (MMF); three patients received triple therapy consisting of prednisolone, tacrolimus, and sirolimus. Less than half (45%) of patients received antibody therapy during the study period. Patients with B-cell cross-matching were considered at high risk of acute rejection and received immunosuppressive therapy with antithymocyte globulin (ATG) induction. The CMV incidence was 14.6%, and 41% of patients had a negative CMV serology result, of whom 56% received kidneys from donors with a positive CMV serology result.
Available data suggest that several factors may contribute to the lower incidence of CMV infection, including CMV seroprevalence in the population, organ donor and recipient serologic status, type and intensity of immunosuppressive drug exposure, and diagnostic methods. In our study, we found that the lower incidence of CMV infection has several possible explanations: (i) most kidney transplant recipients received CMV prophylaxis in the early posttransplant period, with many of these patients receiving long-term oral ganciclovir; (ii) the use of intravenous ganciclovir/oral valganciclovir during antibody treatment of rejection episodes; (iii) lower target levels of cyclosporine and tacrolimus; and (iv) limited use and lower doses of ATG for rejection prophylaxis and treatment.
In this study, no patients with CMV infection relapsed during the follow-up period, and only CMV D/R serologic status and B-cell crossmatch (BXM) were associated with an increased risk of developing CMV infection. We also found that antibody induction therapy was not associated with a higher risk of developing CMV infection in kidney transplant recipients. However, the smaller sample size may explain the lack of association between the studied variables. Alternative explanations should also be considered, such as the increased risk observed in previous studies, possibly due to confounding factors. The lack of association may also be related to lower doses of ATG for induction therapy.
In conclusion, we confirm a lower incidence of CMV infection among kidney transplant recipients in the first 2–5 years after transplantation and that a positive B-cell response to transplantation is being strongly associated with an increased risk of CMV disease after adjusting for all known potential confounders of the association between donor and recipient CMV serostatus and CMV disease.