COVID-19 in renal-transplanted recipients: a narrative review

COVID-19 is an emerging disease mainly associated with Severe Acute Respiratory Syndrome (SARS). This disease causes a cytokine storm release in response to viral infection, and can lead to several systemic complications. Acute kidney injury (AKI) is one of these complications and renal replacement therapy may be necessary for the infected patient. In this context, renal-transplanted recipients (RTR) and patients with chronic kidney diseases are in the risk groups for COVID-19 due to their increased inflammatory state and endothelial dysfunction. Furthermore, maintenance immunosuppressive therapy in RTR can also be another complicating factor, since it influences the response from the immune system against pathogens, including SARS-CoV-2. However, it is believed that the worst outcomes of COVID-19 are mainly caused by an exaggerated inflammatory response than to the direct virus action; therefore, in a hyper-inflammatory state, immunosuppression therapy could be beneficial. This narrative review aims to present the main clinical and laboratory findings of 22 studies involving RTR affected by COVID-19. This review can contribute to the management of COVID-19 and its consequences in this risk group.

Pulmonary fibrosis in dyskeratosis congenita: a case report with a PRISMA-compliant systematic review

Background Dyskeratosis congenita (DC) is a rare genetic disorder of poor telomere maintenance. Pulmonary fibrosis (PF) related to DC is rarely reported. Case presentation A 23-year-old student presented with a four-year history of progressive cough and exertional dyspnea. Physical examination was remarkable for typical mucocutaneous abnormalities. Chest computerized tomography scan revealed interstitial fibrosis. Testing of peripheral blood leukocytes confirmed that his telomeres were 30th percentile of age-matched controls. A heterozygous missense mutation located in exon 22 of PARN gene was identified in the patient by whole exome sequencing. The patient refused danazol therapy and lung transplantation, and died of respiratory failure 2 years later. In addition, this case and 26 reported cases of DC-related PF identified through the comprehensive search of PubMed, Web of Science, WANFANG and CNKI were reviewed. Later-onset PF was observed in 11 patients (40.7%). Radiological usual interstitial pneumonia (UIP) pattern or possible UIP pattern was noted only in half of patients. However, histopathological UIP or probable UIP patterns were found in 63.6% of patients. Age at bone marrow failure (BMF) and the frequency of normal to mild thrombocytopenia in later-onset patients was significantly higher than in early-onset patients (p = 0.017 and p = 0.021, respectively). Age at PF and age at BMF in DC patients with TERC/TERT variants was significantly higher than in those with TINF2 variants or DKC1/NHP2 variants (p = 0.004 and p = 0.003, respectively). The patients with TERT/TERC/RTEL1/PARN variants had a significantly better transplant-free survival than those with TINF2 variants or DKC1/NHP2 variants (p < 0.05). Patients who underwent surgical lung biopsy had significantly worse transplant-free survival than those without lung biopsy (p = 0.042). Worse survival was found in patients with immunosuppression therapy than in those without (p = 0.012). Conclusions It is common for DC-associated PF to occur later in life without significant hematological manifestations. Mutations in the genes encoding different components of the telomere maintenance pathway were associated with clinical phenotypes and prognosis. PF caused by DC should be kept in mind by clinicians in the differential diagnosis of patients with unexplained PF and should be excluded before diagnostic surgical lung biopsy is undertaken or empirical immunosuppression therapy is prescribed.

Different reverse remodelling between left ventricle and right ventricle in fulminant heart failure due to giant cell myocarditis: a case report

Background Giant cell myocarditis (GCM) is a rare cause of fulminant heart failure (HF). The most common presentation is progressive hemodynamic deterioration, and a few cases present with idiopathic complete atrioventricular block (cAVB). The prognosis of GCM is poor, and GCM patients usually die of HF and ventricular arrhythmia unless cardiac transplantation is performed. Few reports have described the effects of treatments such as immunosuppression and detailed reverse remodelling in GCM patients. Case summary A 69-year-old female presented with cAVB. Transvenous pacemaker was implanted via the left subclavian vein. One and a half months later, she exhibited left ventricular dyssynchrony and lower left ventricular ejection fraction (LVEF), resulting in hospitalization for HF. She received cardiac resynchronization therapy; however, this had no apparently positive effects on her cardiac function. To investigate the cause of the lower LVEF, an endomyocardial biopsy was taken from the right ventricular septum. She was diagnosed with GCM and immediately received immunosuppression therapy with prednisolone and ciclosporin. This resulted in the functional recovery of the right ventricle; on the other hand, the left ventricle had still not recovered based on transthoracic echocardiography. Fortunately, she successfully recovered from severe HF without recurrence. Discussion This is a case of fulminant HF due to GCM which initially presented as cAVB. Moreover, this case demonstrates the quite difference of the functional recovery between the left ventricle and the right ventricle with immunosuppression therapy.

Vasculitis ANCA: Alternativas de tratamiento y las expectativas en los pacientes

<b>Background:</b> The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. <b>Methods:</b> A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. <b>Results:</b> Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (<i>n</i> = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], <i>I</i>² = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). <b>Conclusion:</b> This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

Nocardiosis in glomerular disease patients with immunosuppressive therapy

Background Glomerular disease patients have a high risk of infection, which contributes to the progression of disease per se and mortality, especially in those with long-term use of glucocorticoids and (or) immunosuppressive agents. Cases of sporadic nocardiosis have been reported in glomerular disease patients, and this observation was conducted to comprehensively understand the manifestations of and treatments for nocardiosis, which is commonly misdiagnosed as pneumonia or tuberculosis or even as lung cancer or metastatic tumors in glomerular disease patients. Methods We reviewed the demographic characteristics, laboratory abnormalities, radiological features, and treatments of 7 patients with nocardiosis and glomerular disease receiving steroids and immunosuppression therapy at the nephrology department of the Second Xiangya Hospital between 2012 and 2019. Results It was found that all 7 patients had been receiving methylprednisolone for renal disease at a median dose of 20 mg per day and a median duration of 4 months before developing nocardiosis. There were 4 males and 3 females, and the median age was 52.14 years. All 7 patients had hypoalbuminemia at the time of admission. In addition, various cystic abscesses in the subcutaneous tissue, with or without lung and brain involvement, were observed in these patients. Encouragingly, body temperatures returned to normal, and subcutaneous abscesses diminished or disappeared with compound sulfamethoxazole treatment alone or in combination with linezolid, imipenem and mezlocillin/sulbactam. Conclusions It was shown that multisite abscesses, including subcutaneous, pulmonary and cerebral abscesses, were the common manifestations of nocardiosis in glomerular disease patients. Sulfonamide was the first-line antibiotic therapy for nocardiosis, and combinations of other antibiotics were also needed in some serious cases.

Abstract 17238: Taper With Caution: A Case Report of Treatment Response of a Patient With Cardiac Sarcoidosis to Tapering of Steroid Therapy and Initiation of Methotrexate

Introduction: We present a case of a patient with systemic sarcoidosis with cardiac involvement who presented with palpitations and was noted to be in non-sustained ventricular tachycardia (NSVT) after being tapered down the prednisone dose and being started on methotrexate. Clinical Course: 49-year-old female presented with symptoms of palpitations for 10 day prior to presentation with associated lightheadedness. Her past medical history included cardiac sarcoidosis, atrial tachycardia and complete heart block with a pacemaker placement. Upon checking her remote pacemaker interrogation during the current admission she was found to have recurrent episodes of non-sustained ventricular tachycardia. Patient was diagnosed with sarcoidosis 4 months prior to presentation and was started on 50 mg of prednisone which was tapered down to 30 mg 2 months prior to patient’s presentation due to weight gain along with initiation of methotrexate therapy .Patient was started on amiodarone 200 mg daily with a loading dose of 400 TID while admitted. Her prednisone was increased temporarily and weekly methotrexate was continued. The patient was found to have resolution of symptoms and did not have recurrence of arrhythmia on telemetry. She was upgraded to ICD placement during the same admission and was discharged with follow up. Conclusions: Ventricular tachycardia (VT) resulting from myocardial inflammation is the most common arrhythmia in cardiac sarcoidosis (CS), found in up to 23% of the patients. Antiarrhythmic drugs such as amiodarone are standard treatment for VT in patients with CS. However, corticosteroid therapy has shown to be beneficial for ventricular arrhythmias (VA) as demonstrated in some studies while even worsening ventricular arrhythmias in minority of the patients. In our patient, the tapering of the prednisone dose despite introduction of methotrexate resulted in the recurrence of ventricular tachycardia which eventually resolved with the re-administration of the original dose of prednisone. This indicates that more definitive immunosuppression therapy guidelines are required for patients with CS.

Different clinical presentations of two renal transplant recipients with coronavirus disease 2019: a case report

Background The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus-2 has spread rapidly worldwide and disease spread is currently increasing. Data on the clinical picture of transplant recipients and management of the anti-rejection immunosuppressive therapy on COVID-19 infection are lacking. Case presentation We report two cases of COVID-19 infection in renal transplant recipients with variable clinical presentations. The first patient presented with mild respiratory symptoms and a stable clinical course. The second patient had more severe clinical characteristics and presented with severe pneumonia and multi-organ failure. Both patients received a combination therapy including antiviral treatment and reduced immunosuppression therapy and finally recovered. Conclusions We report COVID-19 infection in two renal transplant recipients with a favorable outcome but different clinical courses, which may provide a reference value for treating such patients.