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1.
Transpl Int ; 35: 10448, 2022.
Article in English | MEDLINE | ID: covidwho-1917242

ABSTRACT

The routine surveillance of kidney transplant allografts has relied on imperfect non-invasive biomarkers such as creatinine and urinary indices, while the gold standard allograft biopsy is associated with risk of bleeding, organ injury and sampling errors. Donor derived cell free DNA (dd-cfDNA) is being employed as a biomarker that addresses limitations of these surveillance methods, albeit has inherent drawbacks. This review provides an update on the enhanced understanding of dd-cfDNA and its expanded use beyond the conventional indication of detecting allograft rejection.


Subject(s)
Cell-Free Nucleic Acids , Kidney Transplantation , Biomarkers , Graft Rejection/diagnosis , Humans , Kidney Transplantation/adverse effects , Tissue Donors
4.
Transplant Direct ; 8(1): e1268, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1583924

ABSTRACT

BACKGROUND: Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. METHODS: We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. RESULTS: In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. CONCLUSIONS: Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

5.
Transplant Proc ; 53(4): 1202-1206, 2021 May.
Article in English | MEDLINE | ID: covidwho-1014862

ABSTRACT

Kidney transplant recipients who develop coronavirus disease 2019 (COVID-19) are at increased risk of life-threatening illness, which often requires reducing immunosuppression despite the potential risk of causing an allograft rejection. Herein, we describe the clinical presentation and course of a kidney transplant recipient who acquired COVID-19 and was hospitalized with severe symptoms and hypoxemia. Upon admission, the patient was found to have elevated de novo donor-specific antibodies (DSA) yielding a positive cytotoxicity crossmatch and concurrent elevated plasma donor-derived cell-free DNA (dd-cfDNA) level, indicating a possible ongoing rejection despite improvement in his serum creatinine. Because of persistent positive COVID-19 tests and stable serum creatinine, a kidney allograft biopsy was initially deferred and his dd-cfDNA and DSA were monitored closely postdischarge. Three months later, because of persistent elevated dd-cfDNA and positive DSA, a kidney allograft biopsy was performed, which showed chronic active antibody-mediated rejection. Accordingly, the patient was treated with intravenous immunoglobulin and his maintenance immunosuppressive regimen was increased.


Subject(s)
COVID-19/diagnosis , Graft Rejection/prevention & control , Kidney Transplantation , Antibodies/blood , Antibodies/immunology , COVID-19/complications , COVID-19/virology , Cell-Free Nucleic Acids/blood , Creatinine/blood , Graft Rejection/diagnosis , HLA-DR7 Antigen/immunology , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Oxygen Inhalation Therapy , SARS-CoV-2/isolation & purification , Tacrolimus/blood , Tacrolimus/therapeutic use
6.
Am J Transplant ; 21(7): 2498-2508, 2021 07.
Article in English | MEDLINE | ID: covidwho-960766

ABSTRACT

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < .001), hypertension (69% vs. 44%, p = .001), HIV (7% vs. 1.4%, p = .024), and peripheral vascular disorders (19% vs. 8%, p = .018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = .13), length-of-stay (sHR: 0.9 1.11.4 , p = .5), or mortality (sHR: 0.1 0.41.6 , p = .19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3-4]) (p = .042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.76 0.810.86 , p < .001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.


Subject(s)
COVID-19 , Organ Transplantation , Humans , Inpatients , Organ Transplantation/adverse effects , Pandemics , Retrospective Studies , SARS-CoV-2 , Transplant Recipients
7.
Transplant Proc ; 52(9): 2620-2625, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-899626

ABSTRACT

Kidney transplant recipients who develop symptoms consistent with coronavirus disease 2019 (COVID-19) are bringing unique challenges to health care professionals. Telemedicine has surged dramatically since the pandemic in effort to maintain patient care and reduce the risk of COVID-19 exposure to patients, health care workers, and the public. Herein we present reports of 3 kidney transplant recipients with COVID-19 who were managed using telemedicine via synchronous video visits integrated with an electronic medical record system, from home to inpatient settings. We demonstrate how telemedicine helped assess, diagnose, triage, and treat patients with COVID-19 while avoiding a visit to an emergency department or outpatient clinic. While there is limited information about the duration of viral shedding for immunosuppressed patients, our findings underscore the importance of using telemedicine in the follow-up care for kidney transplant recipients with COVID-19 who have recovered from symptoms but might have persistently positive nucleic acid tests. Our experience emphasizes the opportunities of telemedicine in the management of kidney transplant recipients with COVID-19 and in the maintenance of uninterrupted follow-up care for such immunosuppressed patients with prolonged viral shedding. Telemedicine may help increase access to care for kidney transplant recipients during and beyond the pandemic as it offers a prompt, safe, and convenient platform in the delivery of care for these patients. Yet, to advance the practice of telemedicine in the field of kidney transplantation, barriers to increasing the widespread implementation of telemedicine should be removed, and research studies are needed to assess the effectiveness of telemedicine in the care of kidney transplant recipients.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/therapy , Kidney Transplantation/adverse effects , Pneumonia, Viral/therapy , Postoperative Complications/therapy , Telemedicine/methods , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Female , Humans , Immunocompromised Host/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Postoperative Complications/diagnosis , Postoperative Complications/immunology , SARS-CoV-2
8.
Curr Transplant Rep ; 7(4): 366-378, 2020.
Article in English | MEDLINE | ID: covidwho-898184

ABSTRACT

PURPOSE OF REVIEW: Insufficient knowledge about COVID-19 and the potential risks of COVID-19 are limiting organ transplantation in wait-listed candidates and deferring essential health care in solid organ transplant recipients. In this review, we expand the understanding and present an overview of the optimized management of COVID-19 in solid organ transplant recipients. RECENT FINDINGS: Transplant recipients are at an increased risk of severe COVID-19. The unique characteristics of transplant recipients can make it more difficult to identify COVID-19. Based on the COVID-19 data to date and our experience, we present testing, management, and prevention methods for COVID-19. Comprehensive diagnostic tests should be performed to determine disease severity, phase of illness, and identify other comorbidities in transplant recipients diagnosed with COVID-19. Outpatients should receive education for preventative measures and optimal health care delivery minimizing potential infectious exposures. Multidisciplinary interventions should be provided to hospitalized transplant recipients for COVID-19 because of the complexity of caring for transplant recipients. SUMMARY: Transplant recipients should strictly adhere to infection prevention measures. Understanding of the transplant specific pathophysiology and development of effective treatment strategies for COVID-19 should be prioritized.

9.
BMC Nephrol ; 21(1): 449, 2020 10 27.
Article in English | MEDLINE | ID: covidwho-894994

ABSTRACT

The pandemic of coronavirus disease 2019 (CoVID-19) has been an unprecedented period. The disease afflicts multiple organ systems, with acute kidney injury (AKI) a major complication in seriously ill patients. The incidence of AKI in patients with CoVID-19 is variable across numerous international studies, but the high incidence of AKI and its associated worse outcomes in the critical care setting are a consistent finding. A multitude of patterns and mechanisms of AKI have been elucidated, and novel strategies to address shortage of renal replacement therapy equipment have been implemented. The disease also has had consequences on longitudinal management of patients with chronic kidney disease and end stage kidney disease. Kidney transplant recipients may be especially susceptible to CoVID-19 as a result of immunosuppression, with preliminary studies demonstrating high mortality rates. Increased surveillance of disease with low threshold for testing and adjustment of immunosuppression regimen during acute periods of illness have been recommended.


Subject(s)
Acute Kidney Injury/etiology , Betacoronavirus , Coronavirus Infections/complications , Kidney Failure, Chronic/therapy , Kidney Transplantation , Pneumonia, Viral/complications , Renal Insufficiency, Chronic/drug therapy , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Age Factors , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Critical Care , Healthcare Disparities , Humans , /methods , Incidence , Kidney Failure, Chronic/complications , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Kidney Transplantation/mortality , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Renal Insufficiency, Chronic/complications , Renal Replacement Therapy/instrumentation , Risk Factors , SARS-CoV-2 , Sex Factors , Transplant Recipients , Vulnerable Populations
10.
Transplantation ; 105(1): 170-176, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-889649

ABSTRACT

BACKGROUND: Kidney transplant recipients have higher risk of infectious diseases due to their reliance on immunosuppression. During the current COVID-19 pandemic, some clinicians might have opted for less potent immunosuppressive agents to counterbalance the novel infectious risk. We conducted a nationwide study to characterize immunosuppression use and subsequent clinical outcomes during the first 5 months of COVID-19 pandemic in the United States. METHODS: Using data from the Scientific Registry of Transplant Recipients, we studied all kidney-only recipients in the United States from January 1, 2017, to March 12, 2020 ("prepandemic" era; n = 64 849) and from March 13, 2020, to July 31, 2020 ("pandemic" era; n = 5035). We compared the use of lymphocyte-depleting agents (versus basiliximab or no induction) and maintenance steroids (versus steroid avoidance/withdrawal) in the pandemic era compared with the prepandemic era. Then, we compared early posttransplant outcomes by immunosuppression regimen during the pandemic era. RESULTS: Recipients in the pandemic era were substantially less likely to receive lymphocyte-depleting induction agents compared with their prepandemic counterparts (aOR = 0.400.530.69); similar trends were found across subgroups of state-level COVID-19 incidence, donor type, and recipient age. However, lymphocyte-depleting induction agents were associated with decreased rejection during admission (aOR = 0.110.230.47) but not with increased mortality in the pandemic era (aHR = 0.130.471.66). On the other hand, the use of maintenance steroids versus early steroid withdrawal remained similar (aOR = 0.711.071.62). CONCLUSIONS: The use of lymphocyte-depleting induction agents has decreased in favor of basiliximab and no induction during the COVID-19 pandemic. However, this shift might have resulted in increases in rejection with no clear reductions in posttransplant mortality.


Subject(s)
COVID-19/epidemiology , Kidney Transplantation/methods , SARS-CoV-2 , Adult , Female , Humans , Immunosuppressive Agents/administration & dosage , Lymphocyte Depletion , Male , Middle Aged
11.
Clin Transplant ; 34(12): e14118, 2020 12.
Article in English | MEDLINE | ID: covidwho-852259

ABSTRACT

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008-2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR,1.12 1.963.42 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,1.00 1.813.29 , p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR,1.02 1.542.31 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,1.03 1.311.68 , p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.


Subject(s)
Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Lupus Erythematosus, Systemic/drug therapy , Maintenance Chemotherapy/methods , Scleroderma, Systemic/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Drug Therapy, Combination , Female , Graft Rejection/prevention & control , Graft Survival , Humans , Information Storage and Retrieval , Insurance, Health , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/mortality , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/mortality , Male , Middle Aged , Registries , Retrospective Studies , Scleroderma, Systemic/complications , Scleroderma, Systemic/mortality , Treatment Outcome , United States , Young Adult
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