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Trials ; 24(1): 213, 2023 Mar 22.
Article in English | MEDLINE | ID: covidwho-2262440


BACKGROUND: Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. METHODS: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. DISCUSSION: The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents. TRIAL REGISTRATION: EU CT-Number: 2022-500024-30-00.

Kidney Transplantation , Torque teno virus , Adult , Humans , Tacrolimus/adverse effects , Kidney Transplantation/adverse effects , Quality of Life , Immunosuppression Therapy , Graft Rejection/diagnosis , Graft Rejection/prevention & control , Immunosuppressive Agents/adverse effects
Clin Kidney J ; 13(4): 550-563, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1109189


BACKGROUND: Acute kidney injury (AKI) can affect hospitalized patients with coronavirus disease 2019 (COVID-19), with estimates ranging between 0.5% and 40%. We performed a systematic review and meta-analysis of studies reporting incidence, mortality and risk factors for AKI in hospitalized COVID-19 patients. METHODS: We systematically searched 11 electronic databases until 29 May 2020 for studies in English reporting original data on AKI and kidney replacement therapy (KRT) in hospitalized COVID-19 patients. Incidences of AKI and KRT and risk ratios for mortality associated with AKI were pooled using generalized linear mixed and random-effects models. Potential risk factors for AKI were assessed using meta-regression. Incidences were stratified by geographic location and disease severity. RESULTS: A total of 3042 articles were identified, of which 142 studies were included, with 49 048 hospitalized COVID-19 patients including 5152 AKI events. The risk of bias of included studies was generally low. The pooled incidence of AKI was 28.6% [95% confidence interval (CI) 19.8-39.5] among hospitalized COVID-19 patients from the USA and Europe (20 studies) and 5.5% (95% CI 4.1-7.4) among patients from China (62 studies), whereas the pooled incidence of KRT was 7.7% (95% CI 5.1-11.4; 18 studies) and 2.2% (95% CI 1.5-3.3; 52 studies), respectively. Among patients admitted to the intensive care unit, the incidence of KRT was 20.6% (95% CI 15.7-26.7; 38 studies). Meta-regression analyses showed that age, male sex, cardiovascular disease, diabetes mellitus, hypertension and chronic kidney disease were associated with the occurrence of AKI; in itself, AKI was associated with an increased risk of mortality, with a pooled risk ratio of 4.6 (95% CI 3.3-6.5). CONCLUSIONS: AKI and KRT are common events in hospitalized COVID-19 patients, with estimates varying across geographic locations. Additional studies are needed to better understand the underlying mechanisms and optimal treatment of AKI in these patients.