Clinical characteristics, risk factors and outcome of severe Norovirus infection in kidney transplant patients: a case-control study.

BACKGROUND: Human Norovirus (HuNoV) has recently been identified as a major cause of diarrhea among kidney transplant recipients (KTR). Data regarding risk factors associated with the occurrence of HuNoV infection, and its long-term impact on kidney function are lacking. METHODS: We conducted a retrospective case-control study including all KTR with a diagnosis of HuNoV diarrhea. Each case was matched to a single control according to age and date of transplantation, randomly selected among our KTR cohort and who did not develop HuNoV infection. Risk factors associated with HuNoV infection were identified using conditional logistic regression, and survival was estimated using Kaplan-Meier estimator. RESULTS: From January 2012 to April 2018, 72 cases of NoV diarrhea were identified among 985 new KT, leading to a prevalence of HuNoV infection of 7.3%. Median time between kidney transplantation and diagnosis was 46.5 months (Inter Quartile Range [IQR]:17.8-81.5), and the median duration of symptoms 40 days (IQR: 15-66.2). Following diagnosis, 93% of the cases had a reduction of immunosuppression. During follow-up, de novo Donor Specific Antibody (DSA) were observed in 8 (9%) cases but none of the controls (p = 0.01). Acute rejection episodes were significantly more frequent among cases (13.8% versus 4.2% in controls; p = 0,03), but there was no difference in serum creatinine level at last follow-up between the two groups (p = 0.08). Pre-transplant diabetes and lymphopenia below 1000/mm3 were identified as risks factors for HuNoV infection in multivariate analysis. CONCLUSION: HuNoV infection is a late-onset and prolonged infection among KTR. The current management, based on the reduction of immunosuppressive treatment, is responsible for the appearance of de novo DSA and an increase in acute rejection episodes.