Two-year post-transplantation cytomegalovirus DNAemia in asymptomatic kidney transplant recipients: incidence, risk factors, and outcome.

BACKGROUND: The incidence and the impact of asymptomatic cytomegalovirus (CMV) DNAemia occurring after the first year post transplantation is unknown. METHODS: In this retrospective cross-sectional study, we analyzed the incidence, risk factors, and impact of 2-year post-transplantation asymptomatic CMV DNAemia (2YCD) on graft function. We included 892 consecutive asymptomatic kidney transplant recipients transplanted for at least 2 years and all were monitored using whole blood CMV quantitative nucleic acid amplification testing (CMV-QNAT). RESULTS: Twenty-eight patients displayed 2YCD (3.1%). Using multivariate analysis in 578 patients, we found that female gender (odds ratio [OR] = 2.57, P = 0.02), a past history of CMV drug-resistance mutation (OR = 8.73, P = 0.005), and corticosteroid use (OR = 2.37, P = 0.03) were independently associated with an increased risk of 2YCD. 2YCD was associated with an increased incidence of subsequent CMV disease over the year following its diagnosis (7% vs. 0.6%, P = 0.02). Patients with 2YCD also exhibited a declining estimated glomerular filtration rate more frequently (77%) than patients with a negative CMV-QNAT (56%, P = 0.02). CONCLUSION: 2YCD appears to be a rare entity, which appears to be associated with chronic graft dysfunction.

Hepatitis E virus infection as a new probable cause of de novo membranous nephropathy after kidney transplantation.

Hepatitis E virus (HEV) has been identified as a cause of chronic viral hepatitis in immunocompromised patients. Some glomerular diseases were found to be associated with this infection. We report the first case, to our knowledge, of a kidney transplant recipient who developed an HEV infection and de novo membranous nephropathy (MN) concomitantly. The patient displayed a hepatic cytolysis first and a nephrotic syndrome occurred 3 months later. HEV infection was diagnosed upon positive polymerase chain reaction on plasma and stool samples, and renal allograft biopsy revealed de novo MN. Typical causes of MN were definitively excluded. A 3-month course of ribavirin monotherapy allowed the patient to mount a sustained viral response that was rapidly followed by complete remission of the nephrotic syndrome. The chronology of the onset and remission of both diseases is highly suggestive of a causal relationship between hepatitis E and MN.

Cytomegalovirus DNAemia Requiring (Val)Ganciclovir Treatment for More Than 8 Weeks Is a Key Factor in the Development of Antiviral Drug Resistance.

Background: Prolonged (val)ganciclovir [(V)GCV] exposure for ≥6 weeks is a known predisposing factor for cytomegalovirus (CMV) drug resistance. However, the selection of this threshold was based on limited data. In this study, we sought to reappraise the risk factors for the development of (V)GCV resistance through a specific focus on kidney transplant recipients (KTRs). Methods: This single-center retrospective study included 313 consecutive KTRs treated for a first CMV episode. Adjusted Cox multivariate regression analysis was used for identifying independent risk factors. Results: Antiviral drug resistance was identified in 20 (6%) KTRs. A cumulative (V)GCV exposure for more than 6 weeks (regardless of the viral load) was not associated with antiviral drug resistance (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 0.33-18.30, P = .38). In contrast, persistent CMV DNAemia requiring (V)GCV treatment for more than 8 weeks was the main independent risk factor for antiviral drug resistance (HR = 11.68, 95% CI = 2.62-52.01, P = .001). The (V)GCV treatment for more than 8 weeks was given to 9% and 18% of patients who had persistent or recurrent CMV DNAemia, respectively. These scenarios were associated with the occurrence of drug resistance in 39% and 12% of cases, respectively. Conclusions: Cumulative (V)GCV exposure ≥6 weeks regardless of the viral load is not associated with antiviral drug resistance. In contrast, prolonged exposure to (V)GCV during CMV replication (with a cutoff ³8 weeks) seems to be a key factor.