Ischemia-reperfusion injury (IRI) upon transplantation is one of the most impactful events that the kidney graft suffers during its life. Its clinical manifestation in the recipient, delayed graft ...function (DGF), has serious prognostic consequences. However, the different definitions of DGF are subject to physicians' choices and centers' policies, and a more objective tool to quantify IRI is needed. Here, we propose the use of donor-derived cell-free DNA (ddcfDNA) for this scope.
ddcfDNA was assessed in 61 kidney transplant recipients of either living or deceased donors at 24 h, and 7, 14 and 30 days after transplantation using the AlloSeq cfDNA Kit (CareDx, San Francisco, CA, USA). Patients were followed-up for 6 months and 7-year graft survival was estimated through the complete and functional iBox tool.
Twenty-four-hour ddcfDNA was associated with functional DGF 7.20% (2.35%-15.50%) in patients with functional DGF versus 2.70% (1.55%-4.05%) in patients without it, P = .023 and 6-month estimated glomerular filtration rate (r = -0.311, P = .023). At Day 7 after transplantation, ddcfDNA was associated with dialysis duration in DGF patients (r = 0.612, P = .005) and worse 7-year iBox-estimated graft survival probability (β -0.42, P = .001) at multivariable analysis. Patients with early normalization of ddcfDNA (<0.5% at 1 week) had improved functional iBox-estimated probability of graft survival (79.5 ± 16.8%) in comparison with patients with 7-day ddcfDNA ≥0.5% (67.7 ± 24.1%) (P = .047).
ddcfDNA early kinetics after transplantation reflect recovery from IRI and are associated with short-, medium- and long-term graft outcome. This may provide a more objective estimate of IRI severity in comparison with the clinical-based definitions of DGF.
In an overwhelming demand scenario, such as the SARS-CoV-2 pandemic, pressure over health systems may outburst their predicted capacity to deal with such extreme situations. Therefore, in order to ...successfully face a health emergency, scientific evidence and validated models are needed to provide real-time information that could be applied by any health center, especially for high-risk populations, such as transplant recipients. We have developed a hybrid prediction model whose accuracy relative to several alternative configurations has been validated through a battery of clustering techniques. Using hospital admission data from a cohort of hospitalized transplant patients, our hybrid Data Envelopment Analysis (DEA)—Artificial Neural Network (ANN) model extrapolates the progression towards severe COVID-19 disease with an accuracy of 96.3%, outperforming any competing model, such as logistic regression (65.5%) and random forest (44.8%). In this regard, DEA-ANN allows us to categorize the evolution of patients through the values of the analyses performed at hospital admission. Our prediction model may help guiding COVID-19 management through the identification of key predictors that permit a sustainable management of resources in a patient-centered model.
Introduction
Given the increased COVID-19 observed in kidney transplant recipients (KTRs) and haemodialysis patients, several studies have tried to establish the efficacy of mRNA vaccines in these ...populations by evaluating their humoral and cellular responses. However, there is currently no information on clinical protection (deaths and hospitalizations), a gap that this study aims to fill.
Methods
Observational prospective study involving 1,336 KTRs and haemodialysis patients from three dialysis units affiliated to Hospital Clínic of Barcelona, Spain, vaccinated with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccines. The outcomes measured were SARS-CoV-2 infection diagnosed by a positive RT-PCR fourteen days after the second vaccine dose, hospital admissions derived from infection, and a severe COVID-19 composite outcome, defined as either ICU admission, invasive and non-invasive mechanical ventilation, or death.
Results
Six per cent (18/302) of patients on haemodialysis were infected, of whom four required hospital admission (1.3%), only one (0.3%) had severe COVID-19, and none of them died. In contrast, 4.3% (44/1034) of KTRs were infected, and presented more hospital admissions (26 patients, 2.5%), severe COVID-19 (11 patients, 1.1%) or death (4 patients, 0.4%). KTRs had a significantly higher risk of hospital admission than HD patients, and this risk increased with age and male sex (HR 3.37 and 4.74, respectively).
Conclusions
The study highlights the need for booster doses in KTRs. In contrast, the haemodialysis population appears to have an adequate clinical response to vaccination, at least up to four months from its administration.
Graphical abstract
We aimed to ascertain the interaction and effects of combined reactivations of BK virus and cytomegalovirus on kidney graft function. All consecutive kidney transplant recipients (KTR) between 2003 ...and 2016 were included. Of 1976 patients who received a kidney transplant, 23 (1.2%) presented BKV-associated nephropathy (BKVAN). Factors independently associated with BKVAN were diabetes mellitus (odds ratios (OR) 3.895%, confidence intervals (CI) (1.4–10.5)), acute allograft rejection (OR 2.8 95%, CI (1.1–7.6)) and nephrostomy requirement (OR 4.195%, CI (1.3–13)). Cytomegalovirus infection was diagnosed in 19% of KTR patients. Recipients with BKVAN presented more frequently with cytomegalovirus (CMV) infection compared to patients without BKVAN (39% vs. 19%, p = 0.02). Acute allograft rejection (OR 2.95%, CI (1.4–2.4)) and nephrostomy requirement (OR 2.95%, CI (1.2–3)) were independently associated with CMV infection. Sixteen patients (69%) with BKVAN had graft dysfunction at one-year post-transplant and eight of them (35%) lost their graft. Patients presenting with BKVAN and graft loss presented more frequently a cytomegalovirus infection (OR 2.295%, CI (1.3–4.3)). In conclusion, we found a relation between CMV infection and graft loss in patients presenting BKVAN, suggesting that patients with CMV reactivation should be actively screened for BKV.
Herpes virus infections is not uncommon in solid organ transplantation patients. We report 3 cases with primary Herpes simplex virus type-1 (HSV1) infection with acute liver failure (ALF). This is a ...rare and potentially fatal entity that could be a donor-derived infection. Although the initial clinical presentation is non-specific, it should be considered as a differential diagnosis in HSV-negative serology patients with liver failure and empirical treatment must be started in combination with a drastic reduction of immunosuppression. A strategy of HSV prophylaxis for pre-transplant HSV seronegative patients must be stablished in order to reduce the risk of clinical disease.
•HSV hepatitis is a rare and fatal entity that can be a donor-derived infection.•It should be suspected in highly immunosuppressed transplant patients who develop acute liver failure.•The treatment delay is associated with higher fatality.•In transplant patients with negative HSV serology, prophylaxis is recommended if they are not with prophylaxis for CMV.
In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which included patients from March to May 2020. An inverse probability of treatment weighting from a propensity score to receive AT was used in all statistical analyses, and we applied a bootstrap procedure in order to calculate an estimation of the 2.5th and 97.5th percentiles of odds ratio (OR). outcomes were measured using an ordinal scale determination (OSD). A total of 33 kidney recipients required hospitalization and 54% of them received at least one AT, mainly tocilizumab (42%), followed by anakinra (12%). There was no statistical effect in terms of intensive care unit (ICU) admission, respiratory secondary infections (35% vs. 7%) or mortality (16% vs. 13%) comparing patients that received AT with those who did not. Nevertheless, patients who received AT presented better outcomes during hospitalization in terms of OSD ≥5 ((OR 0.31; 2.5th, 97.5th percentiles (0.10; 0.72)). These analyses indicate, as a plausible hypothesis, that the use of AT in kidney transplant recipients presenting with COVID-19 could be beneficial, even though multicenter randomized control trials using these therapies in transplanted patients are needed.
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