Background and objectivesThe median kidney transplant half-life is 10–15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list.Design, setting, participants, & measurementsIn this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980–2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies “retransplant” versus “remain waitlisted with maintenance dialysis” are reported for different waiting times after first graft loss.ResultsSecond kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, −14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively.ConclusionsSecond kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.

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The authors compared the rate of SARS-CoV-2 infection in kidney transplant recipients among those who did and did not receive a messenger RNA vaccine in the Czech Republic between February and May 2021 while the Alpha variant was predominant.

<b><i>Background:</i></b> Preclinical studies suggested that pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) by ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) may increase local angiotensin-converting enzyme 2 (<i>ACE2</i>) expression. <b><i>Methods:</i></b> In this study, we evaluated the effect of ACEi or ARB treatment on expression of <i>ACE2</i>, <i>ACE</i>, and <i>AGTR1</i> in 3-month protocol kidney allograft biopsies of stable patients using RT-qPCR (<i>n</i> = 48). Protein ACE2 expression was assessed using immunohistochemistry from paraffin sections. <b><i>Results:</i></b> The therapy with RAAS blockers was not associated with increased <i>ACE2, ACE</i>, or <i>ATGR1</i> expression in kidney allografts and also ACE2 protein immunohistochemistry did not reveal differences among groups. <b><i>Conclusions:</i></b> ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.

Of all kidney transplants, half are still lost in the first decade after transplantation.Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss.In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p = .043 and p = .042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p < .001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10-polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.

Letter to the Editor V.P., I.Z., and O.V. participated in research design and performance, data acquisition, data analysis, and article article. I.M. participated in research design, data acquisition, and data analysis. M.R., M.F., J.M., and P.H. participated in data analysis and data acquisition. A.P. participated in data acquisition, data analysis, and article writing. M.M. participated in data acquisition. A.S. participated in sample acquisition and preparation. I.S. participated in data analysis, data acquisition, and article writing.

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