scholarly journals Changing of therapeutic trends between the 1st and 2nd wave did not reduce COVID-19 related mortality of renal transplant recipients: a national registry study.

2021 ◽  
Author(s):  
Bastien Berger ◽  
Marc Hazzan ◽  
Nassim Kamar ◽  
Helene Francois ◽  
Marie Matignon ◽  
...  
Keyword(s):  
National Registry ◽  
High Dose ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Changing Trends ◽  
Maintenance Immunosuppression ◽  
Reduction Of Mortality ◽  
Second Wave ◽  
Related Mortality

SARS-CoV-2 pandemic evolved in two consecutive waves over 2020 (for France: 1st wave from March 1 to July 31; and 2nd wave from August 1 to December 31). Improvements in the management of COVID-19 led to a reduction of mortality rates in hospitalized patients during the second wave. Whether this progress also benefited to kidney transplant recipients (KTR), a population particularly vulnerable to severe COVID-19, remained unclear. In France, 957 KTR were hospitalized for COVID-19 in 2020 and their data were prospectively collected in the French SOT COVID registry. The presentation, management, and outcomes of the 359 KTR diagnosed during the 1st wave were compared to those of the 598 of the 2nd wave. Baseline comorbidities were largely similar between KTR of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs 58.4%, p<0.001) or CNI (32.1% vs 16.6%, p<0.001) was less frequent during the 2nd wave. Hydroxychloroquine and azithromycin that were commonly used during the 1st wave (21.7% and 30.9%, respectively) were almost abandoned during the 2nd. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, p<0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, p=0.48). We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality in KTR. Our data indirectly support the importance of vaccination and monoclonal neutralizing anti-SARS-CoV-2 antibodies to protect KTR from severe COVID-19.

scholarly journals Predictors of disease severity and outcome of hospitalized renal transplant recipients with COVID-19 infection: A systematic review of a globally representative sample

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Irtiza Hasan ◽  
Tasnuva Rashid ◽  
Sarah Suliman ◽  
Hatem Amer ◽  
Razvan M.Chirila ◽  
...  
Keyword(s):  
Systematic Review ◽  
Kidney Transplant ◽  
Disease Severity ◽  
Severe Disease ◽  
Disease Outcome ◽  
High Dose ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Aggregated Data

AbstractIntroduction: COVID-19 presents a special challenge to the kidney transplant population.Methods: A systematic review of articles that examined COVID-19 in kidney transplant recipients was performed. Patients’ demographics, clinical, laboratory and radiological presentations, immunosuppression modification, and COVID-19 specific management were abstracted and analyzed. COVID-19 severity was classified into mild, moderate, and severe. Disease outcome was classified by whether the patient was discharged, still hospitalized, or died.Results: 44 articles reporting individual data and 13 articles reporting aggregated data on 149 and 561 kidney transplant recipients respectively with COVID-19 from Asia, Europe and America fulfilled all inclusion and exclusion criteria. Among studies reporting case specific data, 76% of cases had severe disease. Compared to patients with mild/moderate disease, patients with severe disease had higher CRP, LDH, Ferritin, D-dimer and were more likely to have bilateral lung involvement at presentation and longer time since transplantation (P<0.05 for all). Recipients’ age, gender and comorbidities did not impact disease severity. Patients with severe disease had a more aggressive CNI reduction and more antiviral medications utilization. Outcome was reported on 145 cases, of those 34 (23%) died all with severe disease. Longer duration from transplant to disease diagnosis, hypoxia and higher LDH were associated with mortality (P<0.05). Different immunosuppression reduction strategies, high dose parenteral corticosteroids use and various antiviral combinations did not demonstrate survival advantage. Similar finding was observed for studies reporting aggregated data.Conclusion: COVID-19 in kidney transplant patients is associated with high rate of disease severity and fatality. Higher LDH and longer time since transplantation predicted both disease severity and mortality. None of the COVID-19 specific treatment correlated with, or improved disease outcome in kidney transplant recipients.

scholarly journals Conversion from Calcineurin Inhibitor– to Belatacept-Based Maintenance Immunosuppression in Renal Transplant Recipients: A Randomized Phase 3b Trial

2021 ◽  
Vol 32 (12) ◽  
pp. 3252-3264
Author(s):  
Klemens Budde ◽  
Rohini Prashar ◽  
Hermann Haller ◽  
Maria C. Rial ◽  
Nassim Kamar ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Adverse Events ◽  
Kidney Transplant ◽  
De Novo ◽  
Graft Loss ◽  
Graft Function ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Maintenance Immunosuppression

BackgroundCalcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients.MethodsStable adult kidney transplant recipients 6–60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months.ResultsOverall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, −2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m2 with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder.ConclusionsSwitching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA.Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based, NCT01820572

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

scholarly journals 2658. Meningitis in Kidney Transplant Recipients: TransMéninges, a French Multicentric Retrospective Cohort Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S930
Author(s):  
Yanis Tamzali ◽  
Anne Scemla ◽  
Pierre Taupin ◽  
Sunny Randhawa ◽  
Valérie Moal ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Specific Population ◽  
Gram Negative ◽  
Wide Range

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.

scholarly journals Coronavirus disease 2019 in kidney transplant recipients: a systematic review and meta-analysis

2021 ◽  
Author(s):  
QY Ho ◽  
R Sultana ◽  
TL Lee ◽  
S Thangaraju ◽  
T Kee ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Clinical Presentation ◽  
Meta Analysis ◽  
Kidney Injury ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Presenting Symptoms ◽  
Effect Of Treatment ◽  
Dose Corticosteroid

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.

scholarly journals Effects of Rituximab on the Development of Viral and Fungal Infections in Renal Transplant Recipients

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Samir J. Patel ◽  
Jennifer M. Devos ◽  
Richard J. Knight ◽  
Kyle L. Dawson ◽  
Wadi N. Suki ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Odds Ratio ◽  
Viral Infections ◽  
Fungal Infections ◽  
Graft Function ◽  
Deceased Donor ◽  
Infectious Complications ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background. Rituximab is becoming increasingly utilized in renal transplant recipients; however, its association with infections remains unclear. Methods. We reviewed the incidence of viral and fungal infections in kidney transplant recipients treated with () or without () rituximab (RTX) in addition to standard immunosuppression. Results. Infections occurred in 134 (30%) patients, with a greater proportion in RTX versus no RTX patients (47% versus 28%; ). Viral infections occurred in 44% and 27% of RTX and no RTX patients, respectively (). This was largely driven by the frequency of BK viremia and noncytomegalovirus/non-BK viruses in RTX patients (27% versus 13% () and 15% versus 2% (), resp.). Fungal infections also occurred more often in RTX patients (11% versus 3 %; ). Multivariate analysis revealed deceased donor recipient (odds ratio = 2.5; ) and rituximab exposure (odds ratio = 2.2; ) as independent risk factors for infection. Older patients, deceased donor recipients, those on dialysis longer, and those with delayed graft function tended to be at a greater risk for infections following rituximab. Conclusions. Rituximab is associated with an increased incidence of viral and fungal infections in kidney transplantation. Additional preventative measures and/or monitoring infectious complications may be warranted in those receiving rituximab.

scholarly journals COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence

Nephron ◽  
2020 ◽  
pp. 1-7
Author(s):  
Muhammed Ahmed Elhadedy ◽  
Yazin Marie ◽  
Ahmed Halawa
Keyword(s):  
Renal Transplant ◽  
Kidney Transplant ◽  
Therapy Monitoring ◽  
Intensive Therapy ◽  
Current Evidence ◽  
Intensive Care Treatment ◽  
Renal Transplant Recipients ◽  
Supportive Treatment ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

By April 26, 2020, infections related to coronavirus disease 2019 (COVID-19) affected people from 210 countries and caused 203,818 reported deaths worldwide. A few studies discussed the outcome of COVID-19 in kidney transplant recipients. This short series demonstrates our experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence. We report 8 cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females. The most frequently associated comorbidity was hypertension. The most common presenting features were fever and cough. The main radiological investigation was a portable chest X-ray. Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level. Overall, 1 patient was managed as an outpatient, the remaining 7 required hospital admission, 1 of them referred to the intensive therapy unit. Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs. Seven patients recovered and discharged home to self-isolate. One patient required intensive care treatment and mechanical ventilation. Supportive treatment could be sufficient for the management or to be tried first. We also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public.

scholarly journals Infection-Related Mortality in Recipients of a Kidney Transplant in Australia and New Zealand

2019 ◽  
Vol 14 (10) ◽  
pp. 1484-1492 ◽  
Author(s):  
Samuel Chan ◽  
Elaine M. Pascoe ◽  
Philip A. Clayton ◽  
Stephen P. McDonald ◽  
Wai H. Lim ◽  
...  
Keyword(s):  
New Zealand ◽  
T Cell ◽  
General Population ◽  
Kidney Transplant ◽  
Older Age ◽  
Competing Risk ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Female Sex ◽  
Related Mortality

Background and objectivesThe burden of infectious disease is high among kidney transplant recipients because of concomitant immunosuppression. In this study the incidence of infectious-related mortality and associated factors were evaluated.Design, setting, participants, & measurementsIn this registry-based retrospective, longitudinal cohort study, recipients of a first kidney transplant in Australia and New Zealand between 1997 and 2015 were included. Cumulative incidence of infectious-related mortality was estimated using competing risk regression (using noninfectious mortality as a competing risk event), and compared with age-matched, populated-based data using standardized incidence ratios.ResultsAmong 12,519 patients, (median age 46 years, 63% men, 15% diabetic, 6% Indigenous ethnicity), 2197 (18%) died, of whom 416 (19%) died from infection. The incidence of infection-related mortality during the study period (1997–2015) was 45.8 (95% confidence interval [95% CI], 41.6 to 50.4) per 10,000 patient-years. The incidence of infection-related mortality reduced from 53.1 (95% CI, 45.0 to 62.5) per 10,000 person-years in 1997–2000 to 43.9 (95% CI, 32.5 to 59.1) per 10,000 person-years in 2011–2015 (P<0.001) Compared with the age-matched general population, kidney transplant recipients had a markedly higher risk of infectious-related death (standardized incidence ratio, 7.8; 95% CI, 7.1 to 8.6). Infectious mortality was associated with older age (≥60 years adjusted subdistribution hazard ratio [SHR], 4.16; 95% CI, 2.15 to 8.05; reference 20–30 years), female sex (SHR, 1.62; 95% CI, 1.19 to 2.29), Indigenous ethnicity (SHR, 2.87; 95% CI, 1.84 to 4.46; reference white), earlier transplant era (2011–2015: SHR, 0.39; 95% CI, 0.20 to 0.76; reference 1997–2000), and use of T cell–depleting therapy (SHR, 2.43; 95% CI, 1.36 to 4.33). Live donor transplantation was associated with lower risk of infection-related mortality (SHR, 0.53; 95% CI, 0.37 to 0.76).ConclusionsInfection-related mortality in kidney transplant recipients is significantly higher than the general population, but has reduced over time. Risk factors include older age, female sex, Indigenous ethnicity, T cell–depleting therapy, and deceased donor transplantation.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_08_27_CJN03200319.mp3

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