The impact of vaccination on incidence and outcomes of SARS-CoV-2 infection in patients with kidney failure in Scotland

Background Patients with kidney failure requiring kidney replacement therapy (KRT) are at high risk of complications and death following SARS-CoV-2 infection with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on incidence of infection, hospitalization and death of COVID-19 infection. Methods Study design was an observational data linkage cohort study. Multiple healthcare datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland, from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses and vaccine effectiveness were calculated. Results As of 19th September 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness against infection and hospitalization was 33% (95% CI 0-52) and 38% (95% CI 0-57) respectively. 9.2% of fully vaccinated individuals died within 28 days of a SARS-CoV-2 positive PCR test (7% dialysis patients and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated Scottish population being admitted to hospital or dying death due to COVID19 during that period. Conclusions These data demonstrate a primary vaccine course of two doses has limited impact on COVID-19 infection and its complications in patients treated with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required.

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Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients

Scientific Reports ◽

10.1038/s41598-021-83274-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thomas Duflot ◽

Charlotte Laurent ◽

Anne Soudey ◽

Xavier Fonrose ◽

Mouad Hamzaoui ◽

...

Keyword(s):

Endothelial Function ◽

Kidney Transplant ◽

Plasma Levels ◽

Renal Allograft ◽

Transplant Recipients ◽

Loss Of Function ◽

Kidney Transplant Recipients ◽

Allograft Dysfunction ◽

Allograft Function ◽

The Impact

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

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Use of Anti-Cytokine Therapy in Kidney Transplant Recipients with COVID-19

Journal of Clinical Medicine ◽

10.3390/jcm10081551 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1551

Author(s):

Marta Bodro ◽

Frederic Cofan ◽

Jose Ríos ◽

Sabina Herrera ◽

Laura Linares ◽

...

Keyword(s):

Kidney Transplant ◽

Ordinal Scale ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Kidney Recipients ◽

Secondary Infections ◽

Statistical Effect ◽

Randomized Control ◽

The Impact ◽

To Receive

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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Temporal Changes in the Impact of HLA Mismatching Among Pediatric Kidney Transplant Recipients

Transplantation Journal ◽

10.1097/tp.0000000000002426 ◽

2019 ◽

Vol 103 (6) ◽

pp. 1267-1271 ◽

Cited By ~ 2

Author(s):

Jessica M. Ruck ◽

Annette M. Jackson ◽

Allan B. Massie ◽

Dorry L. Segev ◽

Niraj Desai ◽

...

Keyword(s):

Kidney Transplant ◽

Temporal Changes ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

The Impact

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Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney transplant recipients: Review of 58 cases

F1000Research ◽

10.12688/f1000research.10414.1 ◽

2016 ◽

Vol 5 ◽

pp. 2893 ◽

Cited By ~ 15

Author(s):

Rossana Rosa ◽

Jose F. Suarez ◽

Marco A. Lorio ◽

Michele I. Morris ◽

Lilian M. Abbo ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Acute Rejection ◽

Clinical Outcomes ◽

Kidney Transplant ◽

Graft Survival ◽

Patient Survival ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Serious Infections ◽

The Impact

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV+ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV- to HIV+ adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% (p=0.06) and 82% vs. 100% (p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV+ kidney transplant recipients.

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Effect of Remdesivir on COVID-19 PCR Positivity and Cycle Threshold in Kidney Transplant Recipients

Transplantology ◽

10.3390/transplantology2030028 ◽

2021 ◽

Vol 2 (3) ◽

pp. 291-293

Author(s):

Ryan J. Winstead ◽

Johanna Christensen ◽

Sara Sterling ◽

Megan Morales ◽

Dhiren Kumar ◽

...

Keyword(s):

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cycle Threshold ◽

Transplant Patients ◽

Kidney Transplant Patients ◽

Polymerase Chain ◽

New Diagnosis ◽

The Impact ◽

Median Change

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR.

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FC 028COVID-19 RELATED MORTALITY IN KIDNEY TRANSPLANT AND DIALYSIS PATIENTS: A COMPARATIVE, PROSPECTIVE REGISTRY BASED STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab145.004 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Alexandre Candellier ◽

Eric Jean Goffin ◽

Priya Vart ◽

Marlies Noordzij ◽

Miha Arnol ◽

...

Keyword(s):

Kidney Transplantation ◽

Replacement Therapy ◽

Kidney Transplant ◽

Hemodialysis Patients ◽

Cox Proportional Hazards ◽

Elderly Subjects ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Kidney Replacement Therapy ◽

Adjusted Model

Abstract Background and Aims Studies examining kidney failure patients with COVID-19 reported higher mortality in hemodialysis patients than in kidney transplant recipients. However, hemodialysis patients are often older and have more comorbidities. This study investigated the association of type of kidney replacement therapy with COVID-19 severity adjusting for differences in characteristics. Method Data were retrieved from the European Renal Association COVID-19 Database (ERACODA), which includes kidney replacement therapy patients diagnosed with COVID-19 from all over Europe. We included all kidney transplant recipients and hemodialysis patients who presented between February 1st and December 1st 2020 and had complete information reason for COVID-19 screening and vital status at day 28. The diagnosis of COVID-19 was made based on a PCR of a nasal or pharyngeal swab specimens and/or COVID-19 compatible findings on a lung CT scan. The association of kidney transplantation or hemodialysis with 28-day mortality was examined using Cox proportional-hazards regression models adjusted for age, sex, frailty and comorbidities. Additionally, this association was investigated in the subsets of patients that were screened because of symptoms or have had routine screening. Results A total of 1,670 patients (496 functional kidney transplant recipients and 1,174 hemodialysis patients) were examined. 16.9% of kidney transplant recipients and 23.9% of hemodialysis patients died within 28 days of presentation. In an unadjusted model, the risk of 28-day mortality was 33% lower in kidney transplant recipients compared with hemodialysis patients (hazard ratio (HR): 0.67, 95% CI: 0.52, 0.85). However, in an age, sex and frailty adjusted model, the risk of 28-day mortality was 29% higher in kidney transplant recipients (HR=1.29, 95% CI: 1.00, 1.68), whereas in a fully adjusted model the risk was even 43% higher (HR=1.43, 95% CI: 1.06, 1.93). This association in patients who were screened because of symptoms (n=1,145) was similar (fully adjusted model HR=1.46, 95% CI: 1.05, 2.04). Results were similar when other endpoints were studied (e.g. risk for hospitalization, ICU admission or mortality beyond 28 days) as well as across subgroups. Only age was found to interact significantly, suggesting that the increased mortality risk associated with kidney transplantation was especially present in elderly subjects. Conclusion In this study, kidney transplant recipients had a greater risk of a more severe course of COVID-19 compared with hemodialysis patients when adjusted for age, sex and comorbidities.

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Iron deficiency after kidney transplantation

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa123 ◽

2020 ◽

Author(s):

Joanna Sophia J Vinke ◽

Marith I Francke ◽

Michele F Eisenga ◽

Dennis A Hesselink ◽

Martin H de Borst

Keyword(s):

Quality Of Life ◽

Heart Failure ◽

Immune System ◽

Iron Deficiency ◽

Patient Outcomes ◽

Excess Mortality ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

The Impact

Abstract Iron deficiency (ID) is highly prevalent in kidney transplant recipients (KTRs) and has been independently associated with an excess mortality risk in this population. Several causes lead to ID in KTRs, including inflammation, medication and an increased iron need after transplantation. Although many studies in other populations indicate a pivotal role for iron as a regulator of the immune system, little is known about the impact of ID on the immune system in KTRs. Moreover, clinical trials in patients with chronic kidney disease or heart failure have shown that correction of ID, with or without anaemia, improves exercise capacity and quality of life, and may improve survival. ID could therefore be a modifiable risk factor to improve graft and patient outcomes in KTRs; prospective studies are warranted to substantiate this hypothesis.

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Paternity in male kidney transplant recipients: a French national survey, the PATeRNAL study

BMC Nephrology ◽

10.1186/s12882-020-02115-x ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Annabel Boyer ◽

◽

Thierry Lobbedez ◽

Mohamed Ouethrani ◽

Angélique Thuillier Lecouf ◽

...

Keyword(s):

General Population ◽

Kidney Transplant ◽

Pregnancy Outcomes ◽

Immunosuppressive Agents ◽

Warning Signal ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Still Births ◽

Male Patients ◽

The Impact

Abstract Background There is concern about the impact of immunosuppressive agents taken by male kidney transplant (KT) recipients on the risk of foetal malformations. The aim of our survey was to estimate the paternity rate and the outcomes of pregnancies fathered by kidney transplanted males. Methods This survey analysed 1332 male KT recipients older than 18 years, followed in 13 centres in France. A self-reported questionnaire was used to collect data on the patients, treatments at the time of conception and the pregnancy outcomes. Results The study included data on 349 children from 404 pregnancies fathered by 232 male KT recipients. The paternity rate was 17% (95% CI [15–20]). There were 37 (9%, 95% CI [7–12]) spontaneous abortions, 12 (3%, 95% CI [2–5]) therapeutic abortions, 2 (0.5%, 95% CI [0.1–1]) still births, and 13 (4%, 95% CI [2–6]) malformations reported. Compared to the general population, there was no difference in the proportion of congenital malformations nor unwanted outcomes whether the father was exposed or not to immunosuppressive agents. Conclusions This survey does not provide any warning signal that pregnancies fathered by male patients exposed to immunosuppressive agents, notably the debated MMF/MPA, have more complications than pregnancies in the general population.

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