scholarly journals The Impact of SARS-CoV-2 Infection, and Application of Immunosuppressive Agents in Kidney Transplant Recipients Suffering from COVID-19

2021 ◽  
Vol 14 (10) ◽  
pp. 1054
Author(s):  
Horng-Ta Tseng ◽  
Xiang-Chi Wu ◽  
Chun-Yao Huang ◽  
Chun-Ming Shih ◽  
Yi-Wen Lin ◽  
...  

In December 2019, the COVID-19 pandemic began to ravage the world quickly, causing unprecedented losses in human life and the economy. A statistical study revealed that the proportion of solid organ transplant (SOT) recipients with severe symptoms and deaths after being infected by SARS-CoV-2 is considerably higher than that of non-SOT recipients, and the prognosis is relatively poor. In addition, the clinical manifestation of SOT recipients suffering from COVID-19 is different from that of general COVID-19 patients. Acute kidney injury (AKI) is a common complication in COVID-19 patients, and it is likely more common among SOT recipients infected with SARS-CoV-2. Clinical experts consider that SOT recipients have long-term treatment with immunosuppressants, and the comorbidities are driven by a high rate of severe symptoms and mortality. Orthotopic kidney allograft transplantation is an effective treatment for patients suffering from end-stage kidney disease/kidney failure through which they can easily extend their life. Indeed, kidney transplant recipients have suffered significant damage during this pandemic. To effectively reduce the severity of symptoms and mortality of kidney transplant recipients suffering from COVID-19, precise application of various drugs, particularly immunosuppressants, is necessary. Therefore, herein, we will collate the current clinical experience of treating COVID-19 infection in kidney transplant recipients and discuss the adjustment of patients using immunosuppressive agents in the face of COVID-19.

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Annabel Boyer ◽  
◽  
Thierry Lobbedez ◽  
Mohamed Ouethrani ◽  
Angélique Thuillier Lecouf ◽  
...  

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.


2020 ◽  
Author(s):  
Annabel Boyer ◽  
Thierry Lobbedez ◽  
Mohamed Ouethrani ◽  
Angélique Thuillier Lecouf ◽  
Nicolas Bouvier ◽  
...  

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.


2020 ◽  
Author(s):  
Annabel Boyer ◽  
Thierry Lobbedez ◽  
Mohamed Ouethrani ◽  
Angélique Thuillier Lecouf ◽  
Nicolas Bouvier ◽  
...  

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.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12021-e12021
Author(s):  
Caio Silverio De Souza ◽  
Sergio D. Simon ◽  
Ana Valeria Melo Mendes ◽  
Helena Fragata Torralvo ◽  
Luciene Fabres Ziviani ◽  
...  

e12021 Background: Immunosuppression, whether caused by chronic use of immunosuppressive agents in solid organ transplant or by infection with human immunodeficiency virus (HIV), increases the risk of developing malignancies compared with the general population. This study aims to describe the profile of solid malignancies in immunosuppressed patients followed at the oncology clinic of the Federal University of São Paulo. Methods: Data were collected directly from the medical records of immunosuppressed patients followed in the Department of Clinical Oncology HSP / UNIFESP from January 2001 to January 2011 regarding sex, age, date of cancer diagnosis, tumor histology, primary site, time from beginning of immunosuppression, etiology of immunosuppression and survival,. Results: There were 46 patients (71.7% men). Median age was 47.1 years, 61% kidney transplant recipients and 39% HIV positive. The average time from the start of immunosuppression to the diagnosis of malignancy was 3.75 years in renal transplant recipients and 2.8 years in HIV positive patients. The most prevalent solid tumor in kidney transplant recipients was Kaposi's sarcoma (39.3%) followed by tumors of the gastrointestinal (GI) tract (21.4%) and genitourinary (GU) tract (14.2%). Kaposi's sarcoma was also the most prevalent cancer in HIV positive patients (44.4%) followed by head and neck (H&N) (22.2%) and GU tumors (11.1%). More than 50% of patients are alive and in follow-up. Conclusions: Kaposi's sarcoma, GI, GU and H&N tumors were the most prevalent solid neoplasms in immunosuppressed patients, in both organ transplanted and HIV patients.


Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0005652020
Author(s):  
Sherry G Mansour ◽  
Divyanshu Malhotra ◽  
Michael Simonov ◽  
Yu Yamamoto ◽  
Tanima Arora ◽  
...  

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect any human host, but kidney transplant recipients (KTR) are considered more susceptible based on previous experience with other viral infections. We evaluated rates of hospital complications between SARS-CoV-2 positive KTR and comparator groups. Methods. We extracted data from the electronic health record on hospitalized patients with SARS-CoV-2 testing at six hospitals from March 4th through September 9th, 2020. We compared outcomes between SARS-CoV-2 positive KTR and controls: SARS-CoV-2 positive non-KTR, SARS-CoV-2 negative KTR and SARS-CoV-2 negative non-KTR. Results. Of 31,540 inpatients, 3213 tested positive for SARS-CoV-2. There were 32 SARS-CoV-2 positive and 224 SARS-CoV-2 negative KTR. SARS-CoV-2 positive KTR had higher ferritin levels [1412 (748,1749) vs. 553 (256,1035), p<0.01] compared to SARS-CoV-2 positive non-KTR. SARS-CoV-2 positive KTR had higher rates of ventilation (34% vs. 14%, p<0.01; vs. 9%, p<0.01; vs. 5%, p<0.01), vasopressor use (41% vs. 16%, p<0.01; vs. 17%, p<0.01; vs. 12%, p<0.01) and acute kidney injury (AKI) (47% vs. 15%, p<0.01; vs. 23%, p<0.01; vs. 10%, p<0.01) compared to SARS-CoV-2 positive non-KTR, SARS-CoV-2 negative KTR, and SARS-CoV-2 negative non-KTR, respectively. SARS-CoV-2 positive KTR continued to have increased odds of ventilation, vasopressor use and AKI compared to SARS-CoV-2 positive non-KTR independent of Elixhauser score, Black race and baseline eGFR. Mortality was not significantly different between SARS-CoV-2 positive KTR and non-KTR, but there was a notable trend towards higher mortality in SARS-CoV-2 positive KTR (25% vs. 16%, p=0.15, respectively). Conclusion. Hospitalized SARS-CoV-2 positive KTR had a high rate of mortality and hospital complications such as requiring ventilation, vasopressor use, and AKI. Additionally they had higher odds of hospital complications compared to SARS-CoV-2 positive non-KTR after adjusting for Elixhauser score, Black race and baseline eGFR. Future studies with larger sample size of KTR need to validate our findings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas Duflot ◽  
Charlotte Laurent ◽  
Anne Soudey ◽  
Xavier Fonrose ◽  
Mouad Hamzaoui ◽  
...  

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.


2021 ◽  
Vol 10 (8) ◽  
pp. 1551
Author(s):  
Marta Bodro ◽  
Frederic Cofan ◽  
Jose Ríos ◽  
Sabina Herrera ◽  
Laura Linares ◽  
...  

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.


2019 ◽  
Vol 103 (6) ◽  
pp. 1267-1271 ◽  
Author(s):  
Jessica M. Ruck ◽  
Annette M. Jackson ◽  
Allan B. Massie ◽  
Dorry L. Segev ◽  
Niraj Desai ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2893 ◽  
Author(s):  
Rossana Rosa ◽  
Jose F. Suarez ◽  
Marco A. Lorio ◽  
Michele I. Morris ◽  
Lilian M. Abbo ◽  
...  

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.


Author(s):  
QY Ho ◽  
R Sultana ◽  
TL Lee ◽  
S Thangaraju ◽  
T Kee ◽  
...  

Introduction: The clinical presentation and outcomes of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs) have not been well studied. Methods: We performed a meta-analysis to examine the presenting features, outcomes and the effect of treatment on outcomes of KTRs with COVID-19. Database search was performed up to 5 September 2020 through PubMed, EMBASE, Web of Science, SCOPUS, and CENTRAL. Results: Overall, 23 studies (1373 patients) were included in the review and meta-analysis. The most common presenting symptoms included fever (74.0%, 95% confidence interval [CI] 65.3–81.1), cough (63.3% 95% CI 56.5–69.6) and dyspnoea (47.5%, 95% CI 39.6–55.6). Pooled rates of mortality and critical illness were 21.1% (95% CI 15.3-28.4) and 27.7% (95% CI 21.5–34.8) respectively. Acute kidney injury occurred in 38.9% (95% CI 30.6–48.1) and dialysis was required in 12.4% (95% CI 8.3–18.0) of the cases. Discussion: KTRs with COVID-19 have a similar clinical presentation as the general population but have higher morbidity and mortality. It is uncertain whether high dose corticosteroid or hydroxychloroquine reduces the risks of mortality in KTRs with COVID-19.


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