COVID-19 in Renal Transplant Patients: Epidemiology and Clinical Characteristics
COVID-19 has posed a significant risk to renal transplant recipients, with higher infection rates compared to the general population. Studies have highlighted the prevalence, complications, and patient characteristics associated with COVID-19 in this vulnerable group.
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Presentation Transcript
COVID19 u pacijenata s transplantiranim bubregom Mirna Ale kovi -Halilovi UKC Tuzla
Coronavirus disease 2019 (COVD-19) emerged as a pandemic in December 2019. Infection has spread quickly (A total of >229million people have been diagnosed and > 4,5 million died) Renal transplant (RTx) recipients considered a population at high risk of infection, complications and infection-related death.
The number of RTx patients diagnosed with COVID-19 was higher than in the general population, but the lower threshold for testing may have contributed to its better identification. Toapanta et al., CKJ 2021
ERA-EDTA study from the French and Spanish registry yielded an average infection rate of 14/1000 transplants Jager KJ et al. Kidney Int, 2020 Similar incidences from multicentre studies- USA, Italy and Spain Cravedi P et al., Am J Transplant 2020 Fava` A et al., Am J Transplant 2020 The incidence was 2 5 times higher in renal transplants than in the general population De Meester J et al, J Am Soc Nephrol 2020
Federacija BiH Sarajevo 16/102 Tx pacijenta (15,69%) Tuzla 23/164 (14,2%)
CLINICAL PRESENTATION AND PATIENT CHARACTERISTICS
Fever, cough and shortness of breath in >60% of patients GI symptoms 1/3 of patients Crespo M et al, Transplantation 2020 COVID-19 RTx pts- mean age ~60, males 2/3 and comorbidities (HTA >80%, DM >25%) -correlates with the characteristics of RTx pts Toapanta et al., CKJ 2021
Very frequent major complications: acute kidney injury (hypoperfusion, cytokine storm, and multiorgan failure ) and acute respiratory distress syndrome... Toapanta et al., CKJ 2021
AKI HISTOLOGY ATN- the main finding Su H et al, Kidney Int 2020 High proportion of proteinuria (44 66%) and microhaematuria (27 42%), suggesting direct cytopathic effect Xia P et al., J Am Soc Nephrol 2020 In severe proteinuria, collapsing glomerulopathy, minimal change disease, thrombotic microangiopathy, pauci-immune crescentic glomerulonephritis and cortical necrosis Deshmukh S et al., Renal Fail 2020 Gupta RK et al, BMC Nephrol 2020 Very few cases of T cell or ABMR. May COVID-19 enhance the alloimmune response? Akilesh S et al., Am J Kidney Dis 2020 Chen N et al., Lancet 2020
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) Acute systemic inflammatory response caused by direct or indirect insults to the lung. Incidence in the general population 12 31%, severe in 56 79% Chen N et al., Lancet 2020; Wang D et al., JAMA 2020] Age and the presence of comorbidities the main risk factors Wu C et al., JAMA Intern Med 2020
Federacija BiH Pribli no jednak procenat Tx pacijenata sa lak om klini kom slikom (19%) i onih koji su hospitalizirani (18%) 6% je primljeno u ICU Isti procenat pacijenata sa umjerenom te kom i te kom klini kom slikom (10%)
Management of transplant recipients has been challenging for clinicians and suggested and used strategies are not based on high-quality evidence.
Remdesivir In general population- decreases in-hospital stay, no effect on mortality. Contraindicated if eGFR<30mL/min/1.73 m2 Untily recently, no studies in transplanted population. Multicenter cohort study (51 Tx pts)- well tolerated and safe in renal and hepatic toxicity; randomized trial needed for efficacy Toapanta et al., CKJ 2021 Buxeda et al., KI, 2021
Cytokine storm plays an important role in COVID-19 disease and is associated with death Oto et al. BMC Nephrology 2021 Xu Z et al. Lancet Respir Med. 2020 Efforts have been made to mitigate the immune response with immunomodulators
Tocilizumab may reduce need for mechanica ventilation, but did not improve survival Salama C et al., N Engl J Med 2021 RECOVERY trial- dexamethasone 28-day mortality if oxygen or invasive mechanical ventilation needed, but not if no respiratory support needed RECOVERY Collaborative Group. N Engl J Med 2020 Focus- optimal timing of such immunomodulatory interventions to maximize the therapeutic effect Rizk JG et al., Drugs 2020
IVIG in deteriorating COVID-19 pts- to counteract inflammation and endothelial activation Cao W et al., Open Forum Infect Dis 2020 Convalescent plasma- to transfer passive immunity- the most promising novel therapeutic approaches Shen C et al., JAMA 2020 Maggiore et DESCARTES Working Group, NDT 2020
The most widely used-modification of immunosuppression reducing or suspending the antimetabolite or mToRi CNI was suspended in patients at risk for interaction with protease inhibitors Fava` A et al., Am J Transplant 2020 Chaudhry ZS et al., Am J Transplant 2020 No evidence on optimal management of immunosuppression Above approach like that of other serious viral infections safe- associated with very low incidences of acute rejection
In vitro efficacy of Cy A and FK506 to inhibit the replication of SARS-CoV-1 and other human coronaviruses has been reported; but no clinical evidence for preventing severe COVID-19 or treat cytokine storm Carbajo-Lozoya J et al., Virus Res 2012 In a Turkish cohort (40 RTx pts), previous antirejection treatment was an independent predictor for mortality and the use of Cy as a maintenance immunosuppressant was associated with better survival Demir E et al., Transpl Infect Dis 2020 Study that included 29 RTx pts- Cy based immunosuppression experienced less mortality compared with immunosuppression minimization Rodriguez-Cubillo B et al., Am J Transplant 2020
Spanish registry 423 RTx pts, mortality 28%... after adjusting for age and gender, mortality declined to 15.8%... baseline characteristics rather than the immunosuppressive state or the transplant itself had a remarkable effect on survival. no differences in baseline immunosuppression, but in pts with ARDS, mortality was lower if antimetabolite discontinued Coll E et al., Am J Transplant 2020
not associated with mortality type of transplantation (L vs D donor) time post-transplantation (<1 versus >1 year) comorbidities type of immunosuppression. any treatment strategy with antivirals Nosocomial SARS-CoV-2 infection had the highest mortality rate (77.8%) Cravedi P et al., Am J Transplant 2020
Mortality in SOT recipients is higher than the normal population (between 18 and 30%) Alberici F et al., Kidney Int. 2020 Pereira MR et al., Am J Transplant. 2020 Unclear whether mortality in SOT recipients is higher vs general inpatient population. Large cohort study in hospitalized pts- mortality, ICU care, and mechanical ventilation rates similar between SOT recipients and general non-transplant patients 482 SOT recipients- overall mortality similar to the general population with similar comorbidities Kates OS et al., Clin Infect Dis. 2020 Oto et al., BMC Nephrology 2021
A Belgium study, 46 RTx pts- mortality similar to general population (14% versus 15.3%), but much lower than in dialysis pts (14% versus 29%) De Meester J et al., J Am Soc Nephrol 2020 ERACODA, 305 RTx pts- 28-day mortality 21.3% vs 25% in dialysis pts, older age predominant risk factor for mortality in renal recipients Hilbrands LB et al, NDT 2020
EARLY POSTTx MORTALITY scarce information on early Tx recipients. early Tx recipients subgroup <6 months or <1 year, mortality not different , but with trend towards a higher mortality for the early group Fava` A et al., Am J Transplant 2020 A recent report- 24 recipients within 60 days postTx- mortality 46% Recipients who died were older (61 versus 70 years), received high-dose steroids less frequently (25% versus 82%) and usually needed ventilation support (15% versus 78%) Pascual J et al., Eur Urol 2020 Study with 237 pts, first-year post-Tx, mortality rate 37% Clarke C et al., Kidney Int Rep 2020
OUTCOMES IN KIDNEY RECIPIENTS VS PATIENTS ON THE WAITING LIST Recommended avoiding living-donor Tx and reserving deceased-donor Tx for life-threatening conditions or for hypersensitized patients with a suitable donor Ahn C et al., Transplantation 2020 Registry-based study from France- RTx pts and pts on waiting list, an increase in deaths was detected in both populations (44% vs 42%), explained by COVID-19. Interestingly, the increase was similar in high-risk geographic areas, but in low risk areas the risk for wait-listed pts was 4- fold higher, no additional risk for RTx pts- transplant programmes should not be suspended in geographic areas with a low spread of infection Thaunat O et al., Kidney Int 2020
Federacija BiH Preminulo 8/39 oboljelih Tx pts (20,51%) (COVID19 neg Tx 0,75%) Gubitak grafta u COVID19 poz Tx 5,1%
The COVID-19 pandemic has been challenging for kidney transplantation programmes around the world, with a big impact on transplant policies and in the management of infected and uninfected patients. The rate of infected transplants was high in geographic areas with widespread infection and patient outcomes were compromised due to high rates of complications and COVID-19-related deaths.
In managing infected patients during the pandemic, only the use of steroids and remdesivir has been demonstrated to be useful after performing randomized controlled clinical trials. Since chronic immunosuppression may influence a patient s outcome, different changes based on art and theory were applied. Thus, in the absence of trial-based evidence, we should include transplant patients in prospective studies and registries to help guide optimal care
Kidney transplant recipients experience a high mortality rate compared with the general population, especially during the very early post-transplant period. Despite the fact that some studies report more favourable outcomes in patients with a kidney transplant than in patients on the kidney waiting list, the higher mortality described in the very early post- transplant period would advise against performing a kidney transplant in areas where the spread of infection is high, especially in recipients >60 years of age.
