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Background Norovirus (NoV) infection frequently progresses to chronic disease after kidney transplant (KTx). This study aims to assess potential risk factors helping to determine patients at risk of chronic NoV infection and to analyse the effect of NoV on allograft outcome. Additionally, we assessed the effectiveness of intravenous immunoglobulin (IVIg) therapy for chronic NoV infection. Methods The study enrolled 60 KTx patients requiring hospitalization because of NoV infection. Clinical parameters, severity of NoV infection and potential risk factors were evaluated. Outcome parameters were clinical symptoms, rehospitalizations, persistent shedding of virus and effects on allograft function. Results Patients were divided into 2 groups: 29 had acute NoV infection only, 31 progressed to chronic NoV infection. Chronic NoV infection was defined as a recurrence of clinical symptoms plus redetection of NoV in stool. Lymphocyte-depleting induction therapy and diabetes mellitus were independent risk factors for chronic infection. For patients with chronic NoV infection, length of stay in hospital was significantly prolonged (p= 0.024). Allograft function remained impaired in the chronic NoV group 6 and 12 months after initial admission.IVIg was administered to 18 patients with chronic NoV infection. No further clinical symptoms of NoV infection occurred in 13 (72%) of these patients. However, NoV was still detectable in stool specimens from 10 (77%) of these patients. Conclusions Chronic NoV infection is associated with reduced allograft function. Administration of IVIg to patients with chronic NoV infection seems beneficial in achieving freedom from clinical symptoms, despite limited effects on shedding of virus.

The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) promotes transplant tolerance as well as viral immune escape. HLA-G expression is associated with regulatory elements targeting certain single nucleotide polymorphisms (SNPs) in the HLA-G 3′ untranslated region (UTR). Thus, we evaluated the impact of HLA-G 3′UTR polymorphisms as surrogate markers for BK polyomavirus (BKPyV) replication or nephropathy (PyVAN) and acute cellular and antibody mediated rejection (ACR/AMR) in 251 living-donor kidney-transplant recipient pairs. After sequencing of the HLA-G 3′UTR, fourteen SNPs between +2960 and +3227 and the 14 bp insertion/deletion polymorphism, which arrange as UTR haplotypes, were identified. The UTR-4 haplotype in donors and recipients was associated with occurrence of BKPyV/PyVAN compared to the other UTR haplotypes. While the UTR-4 recipient haplotype provided protection against AMR, the UTR-2 donor haplotype was deleteriously associated with ACR/AMR. Deduction of the UTR-2/4 haplotypes to specific SNPs revealed that the +3003C variant (unique for UTR-4) in donors as well as in recipients is responsible for BKPyV/PyVAN and also provides protection against AMR; whereas the +3196G variant (unique for UTR-2) promotes allograft rejection. Thus, HLA-G 3′UTR variants are promising genetic predisposition markers both in donors and recipients that may help to predict susceptibility to either viral infectious complication of BKPyV or allograft rejection.

Background Transplanting kidneys from deceased donors with hepatitis C virus (HCV) viremia has been controversial for some time. Direct-acting antiviral agents have been shown to be highly effective in treating HCV infection. We report our experience with transplanting kidneys from HCV-positive donors with detectable viremia into HCV-negative recipients, followed by early treatment with a sofosbuvir-based antiviral regimen. Methods Data were collected from seven HCV-negative recipients receiving kidneys from five deceased HCV-viremic donors. Before transplantation, all intentional transplanted recipients had given informed consent regarding the acceptance of an HCV-viremic kidney. Recipients were closely monitored after transplant with measurements of HCV viremia, liver and renal function, and trough levels of immunosuppressive drugs. Results Four donors were infected with HCV genotype 1; the other with HCV genotype 3a. HCV viremia was detectable in all seven renal transplant recipients within 3 days after transplant. After determination of HCV genotype, antiviral treatment with a sofosbuvir-based regimen (sofosbuvir/ledipasvir, n = 4; sofosbuvir/velpatasvir, n = 3) was initiated within a median of 7 days after transplantation and was continued for 8 to 12 weeks. For all recipients, viral load was below the level of detection at the end of treatment, and all exhibited a sustained virologic response 12 weeks later. All recipients exhibited normal liver enzyme activity at the end of treatment. Renal allograft function and trough levels of tacrolimus remained stable. Conclusions Early administration of a sofosbuvir-based regimen to HCV-negative recipients of kidneys from HCV-viremic donors is feasible and safe. The definition of an optimal therapeutic approach warrants further investigation.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a major impact on transplant recipients, with mortality rates up to 20%. Therefore, the effect of established messenger RNA (mRNA)-based SARS-CoV-2 vaccines have to be evaluated for solid organ transplant patients (SOT) since they are known to have poor responses after vaccination. We investigated the SARS-CoV-2 immune response via SARS-CoV-2 IgG detection in 23 renal transplant recipients after two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol. The antibody response was evaluated once with an anti-SARS-CoV-2 IgG CLIA 15.8 +/− 3.0 days after the second dose. As a control, SARS-CoV-2 IgG was determined in 23 healthcare workers (HCW) and compared to the patient cohort. Only 5 of 23 (22%) renal transplant recipients were tested positive for SARS-CoV-2 IgG antibodies after the second dose of vaccine. In contrast, all 23 (100%) HCWs were tested positive for antibodies after the second dose. Thus, the humoral response of renal transplant recipients after two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech, Kronach, Germany) is impaired and significantly lower compared to healthy controls (22% vs. 100%; p = 0.0001). Individual vaccination strategies might be beneficial in these vulnerable patients. OA Förderung 2021

Background The number of patients on waiting lists for repeated kidney transplantation has increased. However, retransplanted patients have a greater surgical and immunological risk than first-time kidney recipients. Methods We retrospectively analysed all kidney recipients that underwent third, fourth or fifth kidney transplantation (Group 3+) at the University Hospital Essen, Essen, Germany from October 1973 to January 2017. A historical cohort of recipients retransplanted with a second kidney (Group 2) served as the control. Donor and recipient demographic data, cold ischaemia time (CIT), warm ischaemia time, overall operation time and methods, transplantectomy of previous kidney grafts, incidence of surgical and immunological complications as well as patient- and death-censored survival were analysed. Results We identified 108 recipients transplanted with the third, fourth or fifth renal allograft. Patients with more than one transplantation had significantly higher surgical risk due to atherosclerosis (P = 0.002) and higher immunological risk due to higher panel reactive antibody levels preoperatively (current panel reactive antibody P = 0.004; highest panel reactive antibody value P = 0.0001). Group 3+ patients had more often undergone previous transplant nephrectomy (P = 0.0001). There was a significant difference in CIT (P = 0.009), overall operative time (P = 0.0001) and post-transplantation thrombotic events (P = 0.02). We could not demonstrate any differences in graft and patient survival. Conclusion Third, fourth and fifth transplant recipients are a high-risk patient cohort. Our results suggest that patient survival after more than three renal transplantations is similar to that of second graft recipients. This supports the concept of repeated kidney retransplantations.

The interaction of major histocompatibility complex class I chain-related protein A (MICA) and its cognate activating receptor natural killer (NK) group 2 member D (NKG2D) receptor plays a significant role in viral immune control. In the context of kidney transplantation (KTx), cytomegalovirus (CMV) frequently causes severe complications. Hypothesizing that functional polymorphisms of the MICA/NKG2D axis might affect antiviral NK and T cell responses to CMV, we explored the association of the MICA-129 Met/Val single nucleotide polymorphism (SNP) (affecting the binding affinity of MICA with the NKG2D receptor), the MICA rs2596538 G/A SNP (influencing MICA transcription), and the NKG2D rs1049174 G/C SNP (determining the cytotoxic potential of effector cells) with the clinical outcome of CMV during the first year after KTx in a cohort of 181 kidney donor-recipients pairs. Univariate analyses identified the donor MICA rs2596538 G allele status as a protective prognostic determinant for CMV disease. In addition to the well-known prognostic factors CMV high-risk sero-status of patients and the application of lymphocyte-depleting drugs, the donor MICA rs2596538 G allele carrier status was confirmed by multivariate analyses as novel-independent factor predicting the development of CMV infection/disease during the first year after KTx. The results of our study emphasize the clinical importance of the MICA/NKG2D axis in CMV control in KTx and point out that the potential MICA transcription in the donor allograft is of clinically relevant importance for CMV immune control in this allogeneic situation. Furthermore, they provide substantial evidence that the donor MICA rs2596538 G allele carrier status is a promising genetic marker predicting CMV viremia after KTx. Thus, in the kidney transplant setting, donor MICA rs2596538 G may help to allow the future development of personal CMV approaches within a genetically predisposed patient cohort. OA Förderung 2018