Νεφρική Ανεπάρκεια στη νόσο Covid-19

Πρόκειται για μία εργασία σε δύο μέρη΄ ένα γενικό, θέμα του οποίου είναι η μελέτη της οξείας νεφρικής βλάβης σε ασθενείς με covid 19 και ένα ειδικό, θέμα του οποίου είναι η συσχέτιση του MVS score με τη βαρύτητα των ιογενών λοιμώξεων του ανώτερου αναπνευστικού. Όσο αφορά το γενικό μέρος πραγματοποιήθηκε μελέτη της βιβλιογραφίας σχετικά με το ζήτημα της επίπτωσης της οξείας νεφρικής βλάβης σε ασθενείς με Covid 19. Αρχικά διαπιστώθηκε ότι η νεφρική βλάβη σχετίζεται συχνά με ιογενείς λοιμωξείς όπως η ηπατίτιδα Β, η ηπατίτιδα C, ο HIV, ο Η1Ν1 και ο Sars Cov 1 παίρνοντας μεγάλη ποικιλία μορφών και με τη διαμεσολάβηση μεγάλης ποικιλίας μηχανισμών. Αντίστοιχα, στο Sars-Cov2 η νεφρική βλάβη είναι μία συχνή επιπλοκή. Σε διάφορες επιδημιολογικές μελέτες φαίνεται ότι η νεφρική βλάβη σε όσους πάσχουν από Covid 19 κυμαίνεται από 20 μέχρι 50% των ασθενών και συσχετίζεται με αυξημένη ηλικία, βαρύτερη κλινική εικόνα καθώς και με την ύπαρξη συννοσηροτήτων (υπέρταση, διαβήτης, χρόνια νεφρική νόσος). Στους ασθενείς που νοσηλεύονται σε μονάδες εντατικής θεραπείας το ποσοστό της νεφρικής βλάβης αγγίζει το 60% και ένα 60% αυτών των ασθενών χρειάζονται συνεδρίες εξωνεφρικής κάθαρσης. Υπάρχει ποικιλία παθοφυσιολογικών μηχανισμών που συσχετίζονται με τη νεφρική βλάβη. Σε κάποιες περιπτώσεις αποδίδεται στην διαταραχή του ισοζυγίου των υγρών, σε κάποιες στην παραγωγή κυτταροκινών και στην κινητοποίηση των ανοσιακών κυττάρων και το πως δρουν στα ποδοκύτταρα, σε κάποιες περιπτώσεις στην απευθείας δράση του ιού στα ποδοκύτταρα. Ιστολογικά η μεγάλη πλειοψηφία των ασθενών παρουσιάζει οξεία σωληναριακή νέκρωση και σε μικρό αριθμό ασθενών παρουσιάζεται μεγάλη ποικιλία ιστολογικών εικόνων (για παράδειγμα θρομβωτική μικροαγγειοπάθεια, ανοσοπενική σπειραματονεφρίτιδα, καταρρέουσα εστιακή τμηματική σπειραματοσκλήρυνση και άλλα). Όσο αφορά την αντιμετώπιση της νεφρικής βλάβης μέχρι στιγμής δεν υπάρχει ειδική αγωγή για τους ασθενείς με νεφρική βλάβη στα πλαίσια του covid 19, ακολουθούνται τα συντηρητικά μέτρα προστασίας της νεφρικής λειτουργίας και αν δεν ανταποκρίνεται ο ασθενής τίθεται σε θεραπεία υποκατάστασης. Η θεραπεία υποκατάστασης πρέπει να ξεκινάει άμεσα σε ασθενείς που δεν μπορούν να διαχειριστούν τον όγκο των υγρών. Αν οι ασθενείς διαχειρίζονται τον όγκο των υγρών χωρίς πρόβλημα, η έναρξη της θεραπείας υποκατάστασης μπορεί να περιμένει. Η νεφρική βλάβη σε ασθενείς με Covid 19 συσχετίζεται με δυσμενή πρόγνωση και θεωρείται ανεξάρτητος παράγοντας κινδύνου τόσο εντός όσο και εκτός της μονάδος εντατικής θεραπείας. Στο ειδικό μέρος περιγράφεται η μελέτη της συσχέτισης της διατηρημένης απάντησης του ξενιστή στις ιογενείς λοιμώξεις όπως εκφράζεται από την Μετα ιική υπογραφή (Meta-virus signature - MVS) με τη βαρύτητα της λοίμωξης. Συλλέχθηκαν δείγματα περιφερικού αίματος από δημόσιες συλλογές δειγμάτων, ταξινομήθηκαν σε διαφορετικές κατηγορίες βαρύτητας και μελετήθηκε το μεταγραφικό προφίλ τους. Αναδείχτηκε ότι το MVS score συσχετίζεται με τη βαρύτητα της νόσου.This study is composed of two parts. In the first part acute kidney injury is studied in patients with covid-19. In the second part the correlation between MVS score and viral diseases' severity is studied. In the first part, literature regarding the incidence of acute kidney injury in covid 19 patients is studied. At first, acute kidney injury's common relation with HBV, HCV, HIV, H1N1 and Sars Cov 1 infection was shown. This relation takes many different forms and is mediated through many different pathogenetic mechanisms. Regarding Sars-Cov-2, acute kidney injury is a fairly common complication. It is shown that acute kidney injury in patients with covid-19 acute kidney injury is observed at 20 to 50% of total patients and is related to age, more severe disease and certain comorbidities (hypertension, diabetes, chronic kidney disease). Acute kidney injury is developed in 60% of patients in the intensive care unit. Out of these patients, 60% need dialysis. Acute kidney injury is related to a variety of pathogenetic mechanisms. Occasionally it is related to fluid imbalance. On other occasions it is related to cytokines production and immune cells mobilization and their influence to podocytes while sometimes virus acts directly on podocytes. Histologically, the majority of patients display acute tubular necrosis. The rest of patients display a large variety of histological finds (for example thrombotic microangiopathy, pauci-immune glomerulonephritis, collpapsing focal segmental glomerulosclerosis and others). Regarding the treatment of kidney injury there is no special treatment for covid 19 patients with acute kidney injury. Conservative measures for protection of kidney function are applied and when a patient does not respond dialysis is started. At patients unable to manage fluid's volume, dialysis should start immediately. At patients who manage efficiently fluid's volume there is no need to hurry. Kidney injury in covid 19 patients is related to bad prognosis and is considered an independent risk factor for patients in intensive care units as well as the general ward. In the second part we studied the relation between conserved host response to viral diseases, as expressed by Meta-Virus Signature (MVS) and disease severity. Peripheral blood samples were collected by public collections, they were classified to different severity categories and their transcriptome profile was studied. MVS score was related to disease severity

Lupus Nephritis: Clinical Picture, Histopathological Diagnosis, and Management

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost every organ of the body and presents with a great variety of clinical features. SLE effect on kidneys, mostly referred to as lupus nephritis, is of special interest for the rheumatologist and nephrologist for three reasons. First, lupus nephritis is one of the commonest types of organ involvement in this disorder, affecting as up to 45% of all patients with SLE. Second, it presents with a great variety of clinical and histopathological findings, and thus, therapy must be tailored accordingly. Third, it greatly affects the morbidity and mortality of SLE patients. Taking these facts into account, this chapter is centered on lupus nephritis from the perspective of the clinical nephrologist and renal pathologist. This chapter elaborates the diversity of clinical features of lupus nephritis, in relation to the different histopathological forms of the disease and the therapeutic options that are available to date, as well as the pathogenesis, natural history, and prognosis of patients with lupus nephritis

Calciphylaxis: A Long Road to Cure with a Multidisciplinary and Multimodal Approach

Calciphylaxis is a rare yet potentially fatal condition, resulting from ectopic calcification of the small arterioles of the dermis with resulting necrotic lesions infection, sepsis, and death. In hemodialysis patients, its prevalence ranges between 1 and 4%, while mortality amounts to 30–80%. We present in here a 45-year-old female on chronic dialysis with morbid obesity, who was admitted for painful nodules in the lower abdomen and necrotic lesions at the lower extremities. Severe uremia and uncontrolled secondary hyperparathyroidism were the main characteristics in this patient, and thus, a clinical diagnosis of calciphylaxis was made. Treatment modalities included wound care plus antibiotics and analgesics, daily hemodialysis, and strategies targeting calcification with sodium thiosulfate, cinacalcet, and non-calcium-containing binders. A crucial factor for overcoming the infection-lesion vicious circle is thorough and daily care of the lesions. Nursing attention was focused on the motivation of her self-care, for the prevention of institutionalization and the psychological support of the patient and her family. The most intriguing feature was the fact that she experienced several exacerbations during the follow-up time. During the final relapse, she was prescribed hyperbaric oxygen sessions that actually put the disease under control thereafter. The good outcome for this patient was probably related to the combination of close follow-up along with a multidisciplinary approach

MPO–ANCA-Positive Granulomatosis with Polyangiitis with Rapidly Progressive Glomerulonephritis and Saddle-Nose Deformity: A Case Report

Early diagnosis and initiation of appropriate immunosuppressive treatment remain the cornerstone of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis at the cost of significant toxicity. In this report, we present a case of a 69-year-old female who presented with advanced renal insufficiency and evidence of pulmonary hemorrhage and was MPO–ANCA-positive with a clinical phenotype of granulomatosis with polyangiitis. Organ involvement included rapidly progressive glomerulonephritis (GN), along with extrarenal manifestations (skin, upper and lower respiratory system involvement, and onset of saddle-nose deformity). Kidney biopsy established the diagnosis of pauci-immune crescentic, sclerotic GN. She received therapy with glucocorticoids and cyclophosphamide, mainly due to life-threatening extra-renal manifestations, such as pulmonary hemorrhage. She avoided vasculitis-related death but she developed severe therapy-related toxicity, resulting in the discontinuation of immunosuppressive therapy. Continuous re-evaluation of patients with ANCA-associated vasculitis in terms of response to immunosuppressive therapy and treatment-related toxicity is crucial for their management

Coupling of Physiological and Proteomic Analysis to Understand the Ethylene- and Chilling-Induced Kiwifruit Ripening Syndrome

International audienceKiwifruit [Actinidia deliciosa (A. Chev.) C.F. Liang et A.R. Ferguson, cv. "Hayward"] is classified as climacteric fruit and the initiation of endogenous ethylene production following harvest is induced by exogenous ethylene or chilling exposure. To understand the biological basis of this "dilemma," kiwifruit ripening responses were characterized at 20°C following treatments with exogenous ethylene (100 μL L(-1), 20°C, 24 h) or/and chilling temperature (0°C, 10 days). All treatments elicited kiwifruit ripening and induced softening and endogenous ethylene biosynthesis, as determined by 1-aminocyclopropane-1-carboxylic acid (ACC) content and ACC synthase (ACS) and ACC oxidase (ACO) enzyme activities after 10 days of ripening at 20°C. Comparative proteomic analysis using two-dimensional gel electrophoresis (2DE-PAGE) and nanoscale liquid chromatography coupled to tandem mass spectrometry (nanoLC-MS/MS) revealed 81 kiwifruit proteins associated with ripening. Thirty-one kiwifruit proteins were identified as commonly regulated by the three treatments accompanied by dynamic changes of 10 proteins specific to exogenous ethylene, 2 to chilling treatment, and 12 to their combination. Ethylene and/or chilling-responsive proteins were mainly involved in disease/defense, energy, protein destination/storage, and cell structure/cell wall. Interactions between the identified proteins were demonstrated by bioinformatics analysis, allowing a more complete insight into biological pathways and molecular functions affected by ripening. The present approach provides a quantitative basis for understanding the ethylene- and chilling-induced kiwifruit ripening and climacteric fruit ripening in general

Comparative physiological and proteomic analysis reveal distinct regulation of peach skin quality traits by altitude

The role of environment in fruit physiology has been established; however, knowledge regarding the effect of altitude in fruit quality traits is still lacking. Here, skin tissue quality characters were analyzed in peach fruit (cv. June Gold), harvested in 16 orchards located in low (71.5 m mean), or high (495 m mean) altitudes sites. Data indicated that soluble solids concentration and fruit firmness at commercial harvest stage were unaffected by altitude. Peach grown at high-altitude environment displayed higher levels of pigmentation and specific antioxidant-related activity in their skin at the commercial harvest stage. Skin extracts from distinct developmental stages and growing altitudes exhibited different antioxidant ability against DNA strand-scission. The effects of altitude on skin tissue were further studied using a proteomic approach. Protein expression analysis of the mature fruits depicted altered expression of 42 proteins that are mainly involved in the metabolic pathways of defense, primary metabolism, destination/storage and energy. The majority of these proteins were up-regulated at the low-altitude region. High-altitude environment increased the accumulation of several proteins, including chaperone ClpC, chaperone ClpB, pyruvate dehydrogenase E1, TCP domain class transcription factor, and lipoxygenase. We also discuss the altitude-affected protein variations, taking into account their potential role in peach ripening process. This study provides the first characterization of the peach skin proteome and helps to improve our understanding of peach's response to altitude

Ozone-induced inhibition of kiwifruit ripening is amplified by 1-methylcyclopropene and reversed by exogenous ethylene

Background: Understanding the mechanisms involved in climacteric fruit ripening is key to improve fruit harvest quality and postharvest performance. Kiwifruit (Actinidia deliciosa cv. 'Hayward') ripening involves a series of metabolic changes regulated by ethylene. Although 1-methylcyclopropene (1-MCP, inhibitor of ethylene action) or ozone (O3) exposure suppresses ethylene-related kiwifruit ripening, how these molecules interact during ripening is unknown. Results: Harvested 'Hayward' kiwifruits were treated with 1-MCP and exposed to ethylene-free cold storage (0 °C, RH 95%) with ambient atmosphere (control) or atmosphere enriched with O3 (0.3 μL L- 1) for up to 6 months. Their subsequent ripening performance at 20 °C (90% RH) was characterized. Treatment with either 1-MCP or O3 inhibited endogenous ethylene biosynthesis and delayed fruit ripening at 20 °C. 1-MCP and O3 in combination severely inhibited kiwifruit ripening, significantly extending fruit storage potential. To characterize ethylene sensitivity of kiwifruit following 1-MCP and O3 treatments, fruit were exposed to exogenous ethylene (100 μL L- 1, 24 h) upon transfer to 20 °C following 4 and 6 months of cold storage. Exogenous ethylene treatment restored ethylene biosynthesis in fruit previously exposed in an O3-enriched atmosphere. Comparative proteomics analysis showed separate kiwifruit ripening responses, unraveled common 1-MCP- and O3-dependent metabolic pathways and identified specific proteins associated with these different ripening behaviors. Protein components that were differentially expressed following exogenous ethylene exposure after 1-MCP or O3 treatment were identified and their protein-protein interaction networks were determined. The expression of several kiwifruit ripening related genes, such as 1-aminocyclopropane-1-carboxylic acid oxidase (ACO1), ethylene receptor (ETR1), lipoxygenase (LOX1), geranylgeranyl diphosphate synthase (GGP1), and expansin (EXP2), was strongly affected by O3, 1-MCP, their combination, and exogenously applied ethylene. Conclusions: Our findings suggest that the combination of 1-MCP and O3 functions as a robust repressive modulator of kiwifruit ripening and provide new insight into the metabolic events underlying ethylene-induced and ethylene-independent ripening outcomes. © 2018 The Author(s)

Ozone-induced inhibition of kiwifruit ripening is amplified by 1-methylcyclopropene and reversed by exogenous ethylene

Abstract Background Understanding the mechanisms involved in climacteric fruit ripening is key to improve fruit harvest quality and postharvest performance. Kiwifruit (Actinidia deliciosa cv. ‘Hayward’) ripening involves a series of metabolic changes regulated by ethylene. Although 1-methylcyclopropene (1-MCP, inhibitor of ethylene action) or ozone (O3) exposure suppresses ethylene-related kiwifruit ripening, how these molecules interact during ripening is unknown. Results Harvested ‘Hayward’ kiwifruits were treated with 1-MCP and exposed to ethylene-free cold storage (0 °C, RH 95%) with ambient atmosphere (control) or atmosphere enriched with O3 (0.3 μL L− 1) for up to 6 months. Their subsequent ripening performance at 20 °C (90% RH) was characterized. Treatment with either 1-MCP or O3 inhibited endogenous ethylene biosynthesis and delayed fruit ripening at 20 °C. 1-MCP and O3 in combination severely inhibited kiwifruit ripening, significantly extending fruit storage potential. To characterize ethylene sensitivity of kiwifruit following 1-MCP and O3 treatments, fruit were exposed to exogenous ethylene (100 μL L− 1, 24 h) upon transfer to 20 °C following 4 and 6 months of cold storage. Exogenous ethylene treatment restored ethylene biosynthesis in fruit previously exposed in an O3-enriched atmosphere. Comparative proteomics analysis showed separate kiwifruit ripening responses, unraveled common 1-MCP- and O3-dependent metabolic pathways and identified specific proteins associated with these different ripening behaviors. Protein components that were differentially expressed following exogenous ethylene exposure after 1-MCP or O3 treatment were identified and their protein-protein interaction networks were determined. The expression of several kiwifruit ripening related genes, such as 1-aminocyclopropane-1-carboxylic acid oxidase (ACO1), ethylene receptor (ETR1), lipoxygenase (LOX1), geranylgeranyl diphosphate synthase (GGP1), and expansin (EXP2), was strongly affected by O3, 1-MCP, their combination, and exogenously applied ethylene. Conclusions Our findings suggest that the combination of 1-MCP and O3 functions as a robust repressive modulator of kiwifruit ripening and provide new insight into the metabolic events underlying ethylene-induced and ethylene-independent ripening outcomes

The impact of sodium nitroprusside and ozone in kiwifruit ripening physiology: A combined gene and protein expression profiling approach

Background and Aims Despite their importance in many aspects of plant physiology, information about the function of oxidative and, particularly, of nitrosative signalling in fruit biology is limited. This study examined the possible implications of O3 and sodium nitroprusside (SNP) in kiwifruit ripening, and their interacting effects. It also aimed to investigate changes in the kiwifruit proteome in response to SNP and O3 treatments, together with selected transcript analysis, as a way to enhance our understanding of the fruit ripening syndrome. Methods Kiwifruits following harvest were pre-treated with 100∈μm SNP, then cold-stored (0°C, relative humidity 95%) for either 2 or 6 months in the absence or in the presence of O3 (0·3∈μL L-1), and subsequently were allowed to ripen at 20°C. The ripening behaviour of fruit was characterized using several approaches: together with ethylene production, several genes, enzymes and metabolites involved in ethylene biosynthesis were analysed. Kiwifruit proteins were identified using 2-D electrophoresis coupled with nanoliquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Expression patterns of kiwifruit ripening-related genes were also analysed using real-time quantitative reverse transcription-PCR (RT-qPCR). Key Results O3 treatment markedly delayed fruit softening and depressed the ethylene biosynthetic mechanism. Although SNP alone was relatively ineffective in regulating ripening, SNP treatment prior to O3 exposure attenuated the O3-induced ripening inhibition. Proteomic analysis revealed a considerable overlap between proteins affected by both SNP and O3. Consistent with this, the temporal dynamics in the expression of selected kiwifruit ripening-related genes were noticeably different between individual O3 and combined SNP and O3 treatments. Conclusions This study demonstrates that O3-induced ripening inhibition could be reversed by SNP and provides insights into the interaction between oxidative and nitrosative signalling in climacteric fruit ripening. © 2015 The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company

Immune responses of patients on maintenance hemodialysis after infection by SARS-CoV-2: a prospective observational cohort study

Abstract Background Immune dysregulation in patients with acute COVID-19 under chronic hemodialysis (CHD) is fully not elucidated. The changes of mononuclear counts and mediators before and after HD and associations with final outcome were studied. Method In this prospective study, hospitalized patients with moderate-to-severe COVID-19 under CHD and matched comparators under HD were analyzed for their absolute counts of lymphoid cells and circulating inflammatory mediators. Blood samples were collected before start and at the end of the first HD session; dialysate samples were also collected. Result Fifty-nine patients with acute COVID-19 under CHD and 20 uninfected comparators under CHD were enrolled. Circulating concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-10, interferon-γ and platelet-derived growth factor-A were increased in patients. Concentrations of mediators did not differ before and after HD. Significant decreases of CD4-lymphocytes and CD19-lymphocytes were found in patients. The decrease of the expression of HLA-DR on CD14-monocytes was associated with unfavorable outcome (defined as WHO-CPS 6 or more by day 28); increased counts of CD19-lymphocytes were associated with better outcomes. Conclusion Patients under CHD develop an inflammatory reaction to SARS-CoV-2 characterized by increase of inflammatory mediators, decrease of circulating T-lymphocytes and decrease of the expression of HLA-DR on CD14-monocytes