scholarly journals Immunosuppressant Management in Renal Transplant Patients with COVID-19

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Elham Ahmadian ◽  
Sepideh Zununi Vahed ◽  
Shakar Mammadova ◽  
Sima Abediazar

The coronavirus disease 2019 (COVID-19) pandemic poses a special risk for both immunosuppressed patients, especially transplant recipients. Although the knowledge about this infection is growing, many uncertainties remain, particularly regarding the kidney. Kidney transplant recipients (KDRs) should be considered immunocompromised hosts since a potential risk for infection, comorbidity, and immunosuppression exposure exists. Additionally, the management of immunosuppressive agents in KDRs remains challenging. Potential drug interactions with immunosuppressive treatment escalated the risk of unwanted side effects. In this review, we aimed to attain an augmented awareness and improved management immunosuppressant for COVID-19 KDRs.

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Theresa Dornieden ◽  
Benjamin Wilde ◽  
Johannes Korth ◽  
Kai Werner ◽  
Peter A. Horn ◽  
...  

Kidney transplantation is the therapy of choice for patients with end stage renal disease. Due to immunosuppressive treatment, patients are at risk for opportunistic infections. Cytomegalovirus (CMV) reactivation is highly relevant in kidney transplant recipients because it occurs—depending on the serological constellation of the donor and recipient—in more than half of the patients and influences patient outcome. Patients with CMV reactivation show decreased allograft and overall survival. Previous studies could demonstrate that transplant patients often show weak CMV-specific immunity. Besides immunosuppressive treatment, additional mechanisms may reduce CMV-specific immunocompetence such as enhanced negative costimulation. Hence, the aim of this study was to investigate if the function of CMV-specific cells of kidney transplant recipients could be restored by a modulation of costimulatory molecules. To address this question, lymphocytes of kidney transplant patients were stimulated with CMV-specific antigens and incubated with programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), or B- and T-lymphocyte attenuator (BTLA) antibodies. Afterwards, the IFN-γ, IL-21, and IL-17A production was measured by the ELISpot assay. It could be shown that a blockade of the ligand PD-L1 resulted in an increased CMV-specific IFN-γ, IL-21, and IL-17A secretion. The blockade of the receptor PD-1 distinctly enhanced the production of IL-21. BTLA antibodies, however, led only to a marginal increase of CMV-specific IFN-γ and of IL-21 production. Experiments in healthy controls could confirm the results of the kidney transplant recipients. Furthermore, they could demonstrate that treatment with the immunosuppressive drug tacrolimus resulted in decreased CMV-specific IFN-γ and of IL-21 production. Thus, our study could show for the first time that the blockade of the PD-L1/PD-1 pathway also modulates CMV-specific Th21 and Th17 cell function in kidney transplant recipients. Further studies are mandatory to clarify the role of Th21 and Th17 cells in CMV control of these patients.


Author(s):  
Burcu Kaya ◽  
Dilek Barutcu Atas ◽  
Elif Tigen Tükenmez ◽  
Ebru Asicioglu ◽  
Hakki Arikan ◽  
...  

Aim: Kidney transplant patients are amongst the high-risk groups for severe Covid 19. To date, no specific antiviral agent has been found uniformly effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Favipiravir, the recommended drug by The Turkish Ministry of Health, was uniformly supplied to all patients diagnosed to have COVID 19 with a positive nasopharyngeal swap PCR test. The aim of our study was to retrospectively compare our kidney transplant recipients who developed COVID-19 infection started on Favipiravir to those who did not use Favipiravir for the clinical course of the disease with a special emphasis on the occurrence of side effects/adverse events. Methods: Thirty-seven consecutive KT recipients with a median age of 46 years and of whom 62.2% were women; 8 deceased /29 living related donor, with a 8.0 (5.5-12.5) years median duration of transplantation were included in the study. Results: Twenty-six (70.3%) patients received Favipiravir, 11(29.7%) did not. There was no statistical significance in baseline demographic, clinical and laboratory findings between the groups except that the Favipiravir group was older and had a higher requirement of oxygen treatment. There was no statistically significant difference in the course and outcome of COVID-19 infection, in the occurrence of side effects/adverse events related to Favipiravir between the two groups. Laboratory data at baseline, day7 and 30 were also comparable between the groups. Conclusion: Although the efficacy of Favipiravir in the treatment of COVID-19 infection is currently controversial, Favipiravir can safely be used in kidney transplant patients.


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.


JMS SKIMS ◽  
2020 ◽  
Vol 23 (3) ◽  
Author(s):  
Mohmad Hussian Mir ◽  
Tariq Ahmad Bhat ◽  
Khalid Parvez Sofi ◽  
Imtiyaz Ahmad Wani ◽  
Muzafar Maqsood Wani

Immune check point inhibitors (ICPIs) are a new class of anti-neoplastic agents being increasingly used by oncologists to treat various malignancies. These drugs have been associated with varied side effects and have a nephrotoxic potential. Many cases of ICPI induced acute kidney injury are increasingly being reported. Their use in CKD patients on dialysis as well as in kidney transplant recipients is associated with various challenges. This review discusses the use of ICPIs in CKD, dialysis and renal transplant patients and their nephrotoxic potential  


2021 ◽  
Vol 2 (3) ◽  
pp. 253-263
Author(s):  
Het Patel ◽  
Nikhil Agrawal ◽  
Voravech Nissaisorakarn ◽  
Ridhi Gupta ◽  
Francesca Cardarelli

Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S332-S332
Author(s):  
Anna Hardesty ◽  
Aakriti Pandita ◽  
Yiyun Shi ◽  
Kendra Vieira ◽  
Ralph Rogers ◽  
...  

Abstract Background Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19. Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses. To our knowledge, no case-control study of COVID-19 in OTR has been published to-date. Methods We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020. After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls). All patients were discharged from the hospital or died. Results 16 KTR had COVID-19. All 3 KTR off IS, who were excluded from further analyses, survived. Median age was 54 (range: 34–65) years; 5/13 KTR (38.4%) were men. Median time from transplant was 41 (range: 1–203) months. Two KTR, both transplanted >10 years ago, were managed as outpatients. IS was reduced in 12/13 (92.3%), most often by discontinuation of the antimetabolite. IL6 levels were >1,000 (normal: < 5) pg/mL in 3 KTR. Tacrolimus or sirolimus levels were >10 ng/mL in 6/9 KTR (67%) (Table 1). Eleven KTR were hospitalized (84.6%) and matched with 44 controls. One KTR, the only one treated with hydroxychloroquine, died (CFR 5.8%; 7.6% in KTR on IS; 9% in hospitalized KTR on IS). Four controls died (CFR: 9%; state CFR: 5.2%; inpatient CFR: 16.6%). There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls. Four KTR (30.7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab. KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2). Table 1 Table 2 Conclusion Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients. Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction. Extremely high IL6 levels were common. The role of IS and potential benefits from investigational treatments remain to be elucidated. A larger multi-institutional study is underway. Disclosures All Authors: No reported disclosures


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S930
Author(s):  
Yanis Tamzali ◽  
Anne Scemla ◽  
Pierre Taupin ◽  
Sunny Randhawa ◽  
Valérie Moal ◽  
...  

Abstract Background The management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population. Methods We retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected. Results Meningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%). The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively. Conclusion Meningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population. Disclosures All authors: No reported disclosures.


2021 ◽  
Vol 2 (3) ◽  
pp. 291-293
Author(s):  
Ryan J. Winstead ◽  
Johanna Christensen ◽  
Sara Sterling ◽  
Megan Morales ◽  
Dhiren Kumar ◽  
...  

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.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anupma Kaul ◽  
Dharmendra Bhaduria ◽  
Narayan Prasad ◽  
Amit Gupta

Abstract Background and Aims Rituximab is an anti CD 20 agent used widely in renal transplant recipients. Its use is associated with various infections;however, its association with Tuberculosis (TB) is not well established and has not been studied in post renal transplantation patients. Method This is a single centre, retrospective analysis of 56 renal transplant recipients who received rituximab for various reasons and 287 post renal transplant patients who did not receive rituximab during the study period from January 2013 to June 2017. The association between use of rituximab and incidence of TB was studied. Other factors associated with tuberculosis were also investigated. Results Baseline characteristics were similar in both the groups. Mean time for occurrence of TB was 18.4 + 10.6 months after renal transplantation. Rituximab use was not significantly associated with tuberculosis or any other infection. Higher number of rejection episodes (60% vs 32.72%, p=0.029) was the only factor associated with greater incidence of TB. However, no specific type of rejection was associated with tuberculosis. Use of plasmapheresis in post transplant period for treatment of humoral rejections was associated with significantly higher incidence of TB (33.33% vs 13.41%, p=0.031), however when pre- transplant plasmapheresis was also considered, there was no significant difference. The choice of induction agent was not associated with higher incidence of TB. Conclusion Use of rituximab is not associated with higher incidence of TB when compared to other immunosuppressive agents. Routine screening and prophylaxis may not be advisable especially in a country like India with high prevalence of TB; as it will further delay transplantation and may adversely affect the outcome of the patients.


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