ABSTRACT
Cellular immunotherapy consists in using the cells of the immune system as a therapeutic weapon. In this constantly evolving field, the therapeutic strategies developed at the University Hospital of Liege are hematopoietic stem cell transplantation, mesenchymal stromal cells and targeted therapy with CAR-T cells (Chimeric Antigen Receptor T cells). The first two modalities represent a form of non-targeted cell therapy that has been developed over the past decades. While hematopoietic stem cell transplantation is established as the reference treatment for many hematological diseases, mesenchymal stromal cells are still under investigation in various pathologies (notably Crohn's disease, organ transplantation, COVID-19 and pulmonary fibrosis). By contrast, CAR-T cells represent a recently developed and extremely promising targeted immunotherapy. This therapeutic approach has already revolutionized the treatment of B-cell lymphopathies, and has the potential to do the same for many other diseases in the near future.
ABSTRACT
BACKGROUND AND AIMS: Kidney damage has been reported in COVID-19 patients. Despite numerous reports about COVID-19-associated nephropathy, the factual presence of the SARS-CoV-2 in the renal parenchyma remains controversial. METHOD: We consecutively performed 16 immediate (≤3h) post-mortem renal biopsies in patients diagnosed with COVID-19. Kidney samples from 5 patients who died from sepsis and were free from COVID-19 were used as controls. Samples were methodically evaluated by 3 pathologists. Virus detection in the renal parenchyma was performed in all samples by bulk RNA RT-PCR (E and N1/N2 genes), immunostaining (nCoV2019 N-Protein), fluorescent in situ hybridization (nCoV2019-S) and electron microscopy. The first (overview) and second (targeted zoom) columns display positive signal for viral RNA in different renal compartments, including proximal and distal tubules, glomeruli and vessels. nCoV2019-S RNA is in green;Lotus tetragonolobus lectin (LTL) is in red;DAPI is in blue. RESULTS: The mean age of our COVID-19 cohort was 68.2±12.8 years, most of whom were males (68.7%). Proteinuria was observed in 53.3% of cases, while acute kidney injury occurred in 60% of cases. Acute tubular necrosis of variable severity was found in all cases, with no tubular or interstitial inflammation. There was no difference in acute tubular necrosis severity between the patients with COVID-19 versus control samples. Congestion in glomerular and peri-tubular capillaries was respectively observed in 56.3 and 87.5% of patients with COVID-19 compared to 20% of controls, with no evidence of thrombi. The nCoV2019 N-Protein was detected in proximal tubules and also at the basolateral pole of scattered cells of the distal tubules in 9/16 cases. In situ hybridization confirmed these findings. RT-PCR of kidney total RNA detected SARS-CoV-2 N gene in one case. Electron microscopy did not show typical viral inclusions. CONCLUSION: Our immediate post-mortem kidney samples from patients with COVID-19 highlight a congestive pattern of acute kidney injury, with no significant glomerular or interstitial inflammation. Immunostaining and in situ hybridization suggest that SARS-CoV-2 is present in various segments of the nephron.
ABSTRACT
BACKGROUND AND AIMS: Proteinuria, hematuria and acute kidney injury (AKI) are frequently observed in hospitalized patients with COVID-19. However, few data are available on these parameters after hospital discharge. METHOD: This retrospective, observational and monocentric study included 153 hospitalized patients, in whom urine total proteinuria and a1-microglobulin (a marker of tubular injury) were measured. Thirty patients died. Among the 123 survivors, follow-up urine and creatinine analyses were available for 72 patients (after a median of 51 [19;93] days following hospital discharge). RESULTS: The median proteinuria at hospitalization and follow-up (n=72) was 419 [239;748] and 79 [47;129] mg/g, respectively (p<0.0001). The median concentrations of urinary a1-microglobulin (n=66) were 50 [25;81] and 8 [0;19] mg/g, respectively (p<0.0001). Estimating glomerular filtration rate (eGFR) was lower during the hospitalization compared to the follow-up: 81 [62;92] versus 87 [66;98] mL/min/ 1.73m2 (p=0.0222). At follow-up, a decreased renal function was observed in 10/72 (14%) of patients, with 50% of them presenting decreased renal function before COVID-19 hospitalization and others developing severe AKI and/or proteinuria during hospitalization. CONCLUSION: In most hospitalized patients with COVID-19, proteinuria and eGFR significantly improved after hospital discharge. Only patients who developed severe AKI and/or heavy proteinuria will require a specific follow-up by nephrologists.
ABSTRACT
The SARS-CoV-2 virus causes a respiratory distress syndrome, the main symptom of COVID-19 (for "COronaVIrus Disease 2019"). This infectious disease has been causing a major health and socio-economic pandemic since December 2019. The pulmonary alveolus is regarded as the main target of SARS-CoV-2. However, this coronavirus is capable of directly or indirectly affecting other organs, including the kidneys. Here, we summarize the presumed pathophysiology of COVID-19 renal disease. The incidence of acute kidney injury ranges from 0,5 to 22 % of all patients infected with SARS-CoV-2. The need for renal replacement therapy is reported in 5-9 % of patients in intensive care. Histological analysis of renal biopsies mainly shows acute tubular necrosis of varying severity, as well as the congestion of glomerular and peri-tubular capillaries. Endothelitis has been described in few cases. Evidence for a factual inflammation of the glomerulus remains controversial. The medium/long term consequences of COVID-19 nephropathy are unknown and will deserve a tight follow-up.
ABSTRACT
The breakthrough of the secrets of hypertension and the renin-angiotensin-aldosterone system (RAAS) is one of the legends of medicine. The first chapter is the one of Tigerstedt's experiments about renin, and Loesch and Gollblatt's model of renal hypertension. The race to elucidate the mechanisms of angiotensin, angiotensinogen and the angiotensin conversion enzyme cascade, by Braun Menendez and Page teams, is a second chapter. The puzzle of this elegant cascade is completed by aldosterone isolation by the collaboration of Tait spouses and Tadeus Rechstein. As a corollary of these findings, Conn made the first description of primary hyperaldosteronism. The elucidation of RAAS pathophysiology naturally led to the synthesis of the antihypertensive captopril by Ondetti and Cushman, thereby opening the modern era of ACE inhibitors and ARII blockers. In March 2020, a viral pandemic caused by SARS-Cov-2 ignites the entire planet. This new coronavirus uses the RAAS angiotensin conversion enzyme type 2 (ACE-2) as a gateway. The SARS-CoV-2/ACE-2 signalling pathway and its pathological effects on the cardio-respiratory and renal system of these patients initiate a new chapter. The interaction of SARS-Cov-2/ACE-2 axis with anti-hypertensive agents, as well as with ACE-2 activators and ACE-2 homologs, takes a part of an active international study searching for therapeutic targets. This modern research, summarized in this article, will further develop our knowledge of RAAS and, hopefully, will improve the management of COVID-19 patients.
ABSTRACT
Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2020
ABSTRACT
Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2020