Assessing T-Cell Immunity in Kidney Transplant Recipients with Absent Antibody Production after a 3rd Dose of the mRNA-1273 Vaccine.

The vulnerable population of kidney transplant recipients (KTRs) are low responders to COVID-19 vaccines, so specific immune surveillance is needed. The interferon-gamma (IFN-γ) release assay (IGRA) is effective in assessing T cell-mediated immunity. We assessed SARS-CoV-2-directed T cell responses in KTRs with absent antibody production after a third dose of the mRNA-1273 vaccine, using two different IGRAs. A cohort of 57 KTRs, who were actively followed up, received a third dose of the mRNA-1273 vaccine. After the evaluation of humoral immunity to SARS-CoV-2, 14 seronegative patients were tested with two commercial IGRAs (SD Biosensor and Euroimmun). Out of 14 patients, one and three samples were positive by IGRAs with Euroimmun and SD Biosensor, respectively. The overall agreement between the two assays was 85.7% (κ = 0.444). In addition, multivariate linear regression analysis showed no statistically significant association between the IFN-γ concentration, and the independent variables analyzed (age, gender, years since transplant, total lymphocytes cells/mcl, CD3+ cells/mcl, CD3+ CD4+ cells/mcl, CD3+ CD8+ cells/mcl, CD19+ cells/mcl, CD3-CD16+CD56+ cells/mcl) (p > 0.01). In a vulnerable setting, assessing cellular immune response to complement the humoral response may be advantageous. Since the two commercial IGRAs showed a good agreement on negative samples, the three discordant samples highlight the need for further investigations.

Thrombotic Microangiopathy as a Life-Threatening Complication of Long-Term Interferon Beta Therapy for Multiple Sclerosis: Clinical Phenotype and Response to Treatment-A Literature Review.

Thrombotic microangiopathy (TMA) has been observed in some patients receiving interferon beta (IFNß) therapy for relapsing-remitting multiple sclerosis, but little is known about its clinical features and outcomes. We searched the literature to identify cases with IFNß-related TMA and assessed their pattern of organ involvement, the presence of prodromal manifestations, the treatments used, and the outcomes. Thirty-five articles met the inclusion criteria, and data of 67 patients were collected. The median duration of IFNß therapy before the diagnosis of TMA was 8 years, and 56/67 (84%) presented with acute kidney injury (AKI), of which 33 required acute dialysis. All but three patients had manifestations during the four weeks before TMA onset, including flu-like symptoms, headache, and worsening blood pressure control. In only two patients, ADAMTS13 activity was reduced, while 27% had low C3 levels. However, none showed causative genetic mutations associated with development of atypical hemolytic uremic syndrome. All patients discontinued IFNß, 34 (55%) also received plasma exchange, and 12 (18%) received eculizumab. Complete renal recovery was achieved by 20 patients (30%), while 13 (20%) developed end-stage renal disease. Among those with AKI requiring dialysis, eculizumab therapy was associated with a significantly reduced risk of ESRD compared with plasma exchange. Therefore, TMA with features of aHUS mainly occurs after prolonged treatment with IFNß and is preceded by prodromes, which may lead to an early diagnosis before life-threatening complications occur. Eculizumab appears beneficial in cases with severe kidney involvement, which supports a role of the complement system in the pathogenesis of these forms.

De novo collapsing glomerulopathy after kidney transplantation: Description of two cases.

BACKGROUND: Among different forms of de novo focal segmental glomerulosclerosis (FSGS), which can develop after kidney transplantation (KTx), collapsing glomerulopathy (CG) is the least frequent variant, but it is associated with the most severe form of nephrotic syndrome, histological findings of important vascular damage, and a 50% risk of graft loss. Here, we report two cases of de novo post-transplant CG. CLINICAL PRESENTATION: A 64-year-old White man developed proteinuria and worsening of renal function 5 years after KTx. Before the KTx, the patient was affected by an uncontrolled resistant hypertension, despite multiple antihypertensive therapies. Blood levels of calcineurin inhibitors (CNIs) were stable, with intermittent peaks. Kidney biopsy showed the presence of CG. After introduction of angiotensin receptor blockers (ARBs), urinary protein excretion progressively decreased in 6 months, but subsequent follow-up confirmed a progressive renal function decline. A 61-year-old White man developed CG 22 years after KTx. In his medical history, he was hospitalized twice to manage uncontrolled hypertensive crises. In the past, basal serum cyclosporin A levels were often detected above the therapeutic range. Low doses of intravenous methylprednisolone were administered due to the histological inflammatory signs shown on renal biopsy, followed by a rituximab infusion as a rescue therapy, but no clinical improvement was seen. DISCUSSION AND CONCLUSION: These two cases of de novo post-transplant CG were supposed to be mainly caused by the synergic effect of metabolic factors and CNI nephrotoxicity. Identifying the etiological factors potentially responsible for de novo CG development is essential for an early therapeutic intervention and the hope of better graft and overall survival.

Pre-Dialysis B-Line Quantification at Lung Ultrasound Is a Useful Method for Evaluating the Dry Weight and Predicting the Risk of Intradialytic Hypotension.

Intradialytic hypotension (IDH) is a frequent and well-known complication of hemodialysis, occurring in about one third of patients. An integrated approach with different methods is needed to minimize IDH episodes and their complications. In this prospective observational study, recruited patients underwent a multiparametric evaluation of fluid status through a lung ultrasound (LUS) with the quantification of B-lines, a physical examination, blood pressure, NT-proBNP and chest X-rays. The evaluation took place immediately before and at the end of the dialysis session, and the patients were divided into IDH and no-IDH groups. We recruited a total of 107 patients. A pre-dialysis B-line number ≥ 15 showed a high sensitivity in fluid overload diagnosis (94.5%), even higher than a chest X-ray (78%) or physical examination (72%) alone. The identification at the beginning of dialysis of <8 B-lines in the overall cohort or <20 B-lines in patients with NYHA 3−4 class are optimal thresholds for identifying those patients at higher risk of experiencing an IDH episode. In the multivariable analysis, the NYHA class, a low pre-dialysis systolic BP and a low pre-dialysis B-line number were independent risk factors for IDH. At the beginning of dialysis, the B-line quantification at LUS is a valuable and reliable method for evaluating fluid status and predicting IDH episodes. A post-dialysis B-line number <5 may allow for an understanding of whether the IDH episode was caused by dehydration, probably due to due to an overestimation of the dry weight.

Lung ultrasound may help in the differential diagnosis of suspected oligosymptomatic COVID-19 patients on hemodialysis: A case report.

INTRODUCTION: Considering that patients on dialysis showed a poor outcome during COVID-19 pandemic, and that COVID-19 symptoms in dialysis patients are often mild or absent, each dialysis unit should implement local strategies to early recognize patients affected by COVID-19. However, many available SARS-CoV-2 diagnostic tests demonstrated a moderate sensitivity, 70%-80% is probably a reasonable estimate. Consequently, having useful tools for differential diagnosis becomes essential. In this scenario, lung ultrasound (LUS) may have an important role in the evaluation of lung involvement in hemodialysis patients during COVID-19 pandemic. METHODS: We present two cases of hemodialysis patients with COVID-19 pneumonia in whom LUS had a central role in the diagnostic process. Ultrasound images of COVID-19 pneumonia show a typical bilateral pattern characterized by multiple or confluent B-lines with spared areas, thickened and irregular pleural line, and rare subpleural consolidations. LUS showed high accuracy in diagnosing COVID-19 pneumonia. FINDINGS: Despite both patients appeared clinically euvolemic and afebrile, they presented with acute diarrhea and oxygen saturation level of 92%-93%. Although clinical manifestations were mild and not specific in both patients, LUS raised suspicion on the possible COVID-19 diagnosis which was confirmed by a positive nasopharyngeal RT-PCR. DISCUSSION: There are many reasons for a patient on dialysis to present shortness of breath, fever, and multiple B-lines at LUS assessment (such as heart failure, fluid overload, vascular access infection, interstitial pneumonia) but the recognition of typical ultrasound patterns of the COVID-19 pneumonia is helpful for differential diagnosis. LUS may have an important role in the screening process of hemodialysis patients during the COVID-19 pandemic, especially in oligosymptomatic patients before the SARS-CoV-2 diagnostic tests, and in those with suspected symptoms and/or known exposure with unexpected negative SARS-CoV-2 diagnostic tests.