Biomarkers in Renal Vasculitis

The use of biomarkers in glomerular diseases has been subject of investigation during the last decades, as it can provide worthwhile evidence in diagnosis, but also, it can guide treatment and give information about prognosis and response. Renal biopsy is still the compulsory technique to establish diagnosis, and also to offer information about the severity of renal damage. However, as an invasive method, it cannot be regularly performed during follow up, so the need to find and establish measurement of molecules, easily collected, which are associated with disease pathogenesis and predict renal function outcome seems very attractive to nephrologists. The renal complications of systemic vasculitis are very important for the outcome of the disease, and several substances and molecules, such as inflammatory cells, autoantibodies, cytokines, chemokines and growth factors are produced and may serve as biomarkers to provide useful information for diagnosis, follow up of the disease

Pathogenic mechanisms in idiopathic IgA nephropathy: the effect of fish oil administration

IgA nephropathy is the most common form of primary glomerulopathy worldwide. Incidence of the disease ranges from 2 to 50% of all renal biopsies, with great variation in different geographic regions. Polymeric IgA mesangial deposition is the hallmark of the disease. Microscopic appearances on renal histology include a wide spectrum of changes, predominantly those of mesangial cell hyperplasia, mesangial matrix expansion and tubulointerstitial fibrosis. Patients usually present with micro- or macroscopic hematuria, hypertension and mild proteinuria, with well preserved or mildly impaired renal function. Once thought benign, IgA nephropathy has been shown to be potentially associated with progression to end stage renal failure in 20-25% of cases within 20-30 years. The factors and mechanisms implicated in the evolution and progression of the disease are poorly understood. No consensus exists at present on the optimum type of therapy, and the preferred choice in most centers appears to be supportive. In the first part of the study we endeavour to elucidate some of the mechanisms that contribute to pathogenesis of the disease and resulting impairment of renal function. Investigation has been focused in the role of cell-mediated immunity, growth factors, adhesion molecules and terminal complement component (C5b-9). In the second part, the effect of omega3 fatty acids, (fish oils) on renal function was assessed, as compared with symptomatic treatment alone. In addition, an attempt was made to elaborate on the possible mechanisms of the beneficial effect of fish oils in retarding/halting further decline in renal function In the first part of the study, 48 patients with primary IgA nephropathy were included. Diagnosis was established with renal biopsy. Mean age of patients at the time of diagnosis was 36 years (range 17-67), mean blood pressure (MBP) 105±15mmHg, mean serum creatinine l,9±l,5mg/dl, mean glomerular filtration rate (GFR) 77,5±33ml/min and mean urine protein excretion l,3±l,6g/24hr. 24/48 patients (50%) presented with renal failure, and 4/48 (8%) with nephrotic syndrome. On light microscopy we evaluated the degree or severity of several histologic lesions such as mesangial hyperplasia, mesangial matrix expansion, glomerulosclerosis and percentage of cellular/fibrotic crescents in glomeruli, degree of arteriosclerosis, tubulointerstitial infiltration of inflammatory cells, and tubulointerstitial fibrosis. An indirect immunoperoxidase method was used to calculate the numbers of macrophages, a-SMA (+) and PCNA (+) cells, the expression of integrins a3βl and LFA-lβ, adhesion molecule ICAM-1, growth factors TGF-βl and PDGF-BB and of terminal complement component C5b-9. Finally, we studied the correlation between clinical, histologic and immunohistochemistry findings at the time of diagnosis. Macrophages were the predominant cell population in glomeruli. There was a positive correlation between infiltration of macrophages and the number of LFA-lβ (+) cells, the expression of ICAM-1, and a3βl integrin and the deposition of C3 complement component. Glomerular expression of a3βl integrin correlated positively with the number of macrophages and a-SMA (+) cells in glomeruli and the expression of a3βl integrin, and TGF-βl in tubulointerstitium. Glomerular expression of C5b-9 had a positive correlation with the number of PCNA (+) cells and TGF-βl expression in the glomeruli and the tubulointerstitial expression of TGF-βl, a3βl integrin and C5b-9 as well as the severity of tubulointerstitial inflammatory infiltration and fibrosis. The degree of glomerulosclerosis correlated well with the degree of mesangial matrix expansion and the glomerular C5b-9 deposition. There was a direct correlation between mesangial matrix expansion and the degree of mesangial hyperplasia. According to our findings, in plgAN, mesangial deposition of C3 component plays a central role in mesangial hyperplasia and glomerular inflammatory infiltration. Other mechanisms implicated in the progression of glomerulosclerosis are a) proteinuria and the following mesangial matrix expansion, b) the interaction between macrophages and a3βl integrin and the subsequent activation of myofibroblasts and c) increased TGF-βl production and action followed by formation of C5b-9. The severity of tubulointerstitial fibrosis correlated directly with the degree of proteinuria and the severity of glomerulosclerosis. Proteinuria correlated with the tubulointerstitial inflammatory infiltration. Macrophages were the main cellular population in the tubulointerstitium. They correlated positively with a3βl integrin and C5b-9 expression and the number of PCNA (+) cells. These findings suggest that glomerulosclerosis plays a central role in the progression of tubulointerstitial fibrosis. Glomerulosclerosis with the resultant proteinuria leads to activation of tubulointerstitial cells. Macrophages in the tubulointerstitium may subsequently, interact with a3β1 integrin and myofibroblasts or induce C5b-9 and TGF-βl production and activation. Glomerular deposition of a3βl integrin and C5b-9 may also contribute to the above mechanisms by activation of tubulointerstitial cells, especially macrophages. Our findings thus provide compelling evidence that the degree of renal impairment at the time of diagnosis correlates with the severity of glomerulosclerosis as well as the tubulointerstitial macrophage infiltration. In the second part of the study, the effect of fish oil in disease progression was evaluated. Fourty-two patients were randomized to receive either fish oils (Group A, 20 patients) or symptomatic treatment (Group B, 22 patients). Patients in the two groups were similar in terms of clinical, biochemical, histological and immunohistological findings. The follow up period was 59±29 months (range 14-110). At the end of follow up, patients in group A had significantly lower proteinuria levels and better preservation of renal function with a slight increase in GFR, which however was not statistically significant. In group Β there were no significant changes in proteinuria and renal function deteriorated. The effect of ACEIs was also evaluated retrospectively. ACEIs did not have any effect on either proteinuria or renal function, when used as monotherapy. Fish oil given as monotherapy resulted in an improvement in renal function, without, however, any significant effect on proteinuria. The combination of fish oil with ACEI had the most profound beneficial effect on proteinuria level as well as the improvement of renal function. In group B, serum creatinine at the end of the study correlated directly with the extent of glomerulosclerosis, the severity of tubulointerstitial fibrosis, and the tubulointerstitial expression of TGF-βl. In group A the above correlations were not evident at the end as they were in the beginning of the study. Our findings therefore suggest that fish oils may attenuate severity of glomerulosclerosis and interstitial fibrosis probably by affecting the production of TGF-ßl or its action in the tubulointerstitium.H IgA νεφροπάθεια αποτελεί παγκοσμίως τη συχνότερη πρωτοπαθή σπειραματοπάθεια, με συχνότητα που κυμαίνεται ανάλογα με τη γεωγραφική περιοχή, από 2 έως και 50% των νεφρικών βιοψιών. Η νόσος χαρακτηρίζεται από εναπόθεση πολυμερούς IgA ανοσοσφαιρίνης στο μεσάγγειο και ιστολογικά παρατηρείται ένα ευρύ φάσμα αλλοιώσεων μεταξύ των οποίων προέχουν η μεσαγγειακή υπερπλασία, αύξηση της μεσαγγειακής ουσίας, και διάμεσο-σωληναριακή ίνωση. Συνηθέστερα η νόσος εμφανίζει μικρό- ή/και μακροσκοπική αιματουρία, ήπια λευκωματουρία, αρτηριακή υπέρταση και φυσιολογική ή ελαφρά επηρεασμένη νεφρική λειτουργία. Η εξέλιξη της IgAN ποικίλει και ποσοστό 20-25% των ασθενών καταλήγει σε τελικό στάδιο νεφρικής ανεπάρκειας μετά από παρέλευση 20-30 ετών. Οι μηχανισμοί που ευθύνονται τόσο για την εμφάνιση της νόσου όσο και κατά την εξέλιξη της προς νεφρική ανεπάρκεια δεν έχουν ακόμηδιερευνηθεί επαρκώς. Επιπλέον όμως μέχρι σήμερα δεν υπάρχει καθιερωμένη μορφή θεραπείας της IgAN και πολλά κέντρα προτιμούν να αντιμετωπίζουν τους ασθενείς αυτούς συμπτωματικά. Στο πρώτο μέρος της παρούσας μελέτης έγινε προσπάθεια διευκρίνησης των μηχανισμών που συμμετέχουν στην παθογένεια και εξέλιξη της νεφρικής βλάβης και κυρίως στο ρόλο των μηχανισμών της κυτταρικής ανοσίας, στη δράση των αυξητικών παραγόντων, των μορίων προσκόλλησης και του τελικού συμπλέγματος C5b-9 του συμπληρώματος. Στο δεύτερο μέρος της μελέτης εκτιμήθηκε η επίδραση της χορήγησης ω3-λιπαρών οξέων στην εξέλιξη της νεφρικής λειτουργίας των ασθενών και τα αποτελέσματα αυτά συγκρίθηκαν με τα αντίστοιχα της ομάδας ελέγχου. Επιπλέον έγινε προσπάθεια διευκρίνησης των μηχανισμών μέσω των οποίων ασκείται η δράση της θεραπευτικής αυτής αγωγής. Για το σκοπό του πρώτου μέρους μελετήθηκαν προοπτικά 48 ασθενείς με πIgAN στους οποίους η διάγνωση τέθηκε με βιοψία νεφρού. Η μέση ηλικία των ασθενών κατά τη διάγνωση της νόσου ήταν 36 χρόνια (17-67), η ΜΑΠ 105±15mmHg, η μέση τιμή κρεατινίνης ορού l,9±l,5mg/dl, ο μέσος ρυθμός σπειραματικής διήθησης 77,5±33ml/min και η μέση απέκκριση λευκώματος στα ούρα l,3±l,6g/24hr. Νεφρική ανεπάρκεια εμφάνιζαν 24/48 ασθενείς (50%) και νεφρωσικό σύνδρομο 4/48 (8%) ασθενείς. Στη μελέτη με κοινό μικροσκόπιο εκτιμήθηκε στα μεν σπειράματα ο βαθμός της μεσαγγειακής υπερπλασίας και της αύξησης της μεσαγγειακής ουσίας, η έκταση της σπειραματοσκλήρυνσης και το ποσοστό των μηνοειδών σχηματισμών, στο δε ΔΣΧ ο βαθμός της αρτηριοσκλήρυνσης, η φλεγμονώδης διήθηση του διάμεσου ιστού και των ουροφόρων σωληναρίων και η έκταση της ίνωσης του ΔΣΧ. Παράλληλα, με τη χρήση ειδικών μονοκλωνικών αντισωμάτων εκτιμήθηκε η έκταση της κυτταρικής διήθησης του νεφρικού ιστού από μακροφάγα, η ένταση της έκφρασης της α3β1 και της LFA-lβ ιντεγκρίνης, η ένταση της έκφρασης του ICAM-1, ο αριθμός των a-SMA(+) και PCNA(+) κυττάρων, των αυξητικών παραγόντων TGF-βl και PDGF και του τελικού συμπλέγματος C5b-9 του συμπληρώματος. Τέλος, έγιναν παθολογοανατομικές και κλινικοπαθολογοανατομικές συσχετίσεις μεταξύ ιστολογικών, ανοσοϊστοχημικών και κλινικών ευρημάτων των ασθενών κατά τη διάγνωση της νόσου. Τα μακροφάγα αποτελούσαν τον κύριο κυτταρικό πληθυσμό των σπειραμάτων και ο αριθμός τους σχετιζόταν θετικά με τον αριθμό τωνLFA-lβ (+) κυττάρων, με την έκφραση του ICAM-1, της α3β1 ιντεγκρίνης και του C3 κλάσματος του συμπληρώματος. Η σπειραματική έκφραση της α3β1 ιντεγκρίνης εμφάνιζε θετική συσχέτιση με τον αριθμό των a-SMA(+) κυττάρων τόσο στα σπειράματα, όσο και στο ΔΣΧ, τον αριθμό των μακροφάγων στα σπειράματα, και την διάμεσο-σωληναριακή έκφραση της α3β1 ιντεγκρίνης και του TGF-βl. Η σπειραματική έκφραση του C5b-9 σχετιζόταν θετικά με τον αριθμό των PCNA(+) κυττάρων και την έκφραση του TGF-βl στα σπειράματα, τη φλεγμονώδη διήθηση και τη βαρύτητα της ίνωσης του ΔΣΧ, και την έκφραση των TGF-βl, α3β1 και C5b-9 στο ΔΣΧ. Η έκταση της σπειραματοσκλήρυνσης σχετιζόταν θετικά με το βαθμό αύξησης της μεσαγγειακής ουσίας και την εναπόθεση C5b-9 στα σπειράματα. Παράλληλα ο βαθμός αύξησης της μεσαγγειακής ουσίας είχε θετική συσχέτιση με την ένταση της μεσαγγειακής υπερπλασίας. Σύμφωνα με τα ευρήματα μας, η μεσαγγειακή εναπόθεση του C3 αποτελεί ενδεχομένως το πρώτο βήμα που οδηγεί σε μεσαγγειακή υπερπλασία και διήθηση από φλεγμονώδη κύτταρα στα σπειράματα ασθενών με IgAN. Στη συνέχεια, βασικούς μηχανισμούς σπειραματοσκλήρυνσης αποτελούν α) η λευκωματουρία και η συνοδός αύξηση της μεσαγγειακής ουσίας, β) η αλληλεπίδραση μεταξύ μακροφάγων και α3β1 ιντεγκρίνης που έχει ως αποτέλεσμα ενεργοποίηση των μυοϊνοβλαστών και γ) ο σχηματισμός C5b-9 μέσω αύξησης της παραγωγής και δράσης του TGF-βl. Η βαρύτητα της ίνωσης του ΔΣΧ σχετιζόταν θετικά με το βαθμό σπειραματοσκλήρυνσης και τη βαρύτητα της λευκωματουρίας. Παράλληλα, η λευκωματουρία παρουσίαζε θετική συσχέτιση με την ένταση της φλεγμονώδους κυτταρικής διήθησης του ΔΣΧ. Τα μακροφάγα αποτελούσαν τον κύριο κυτταρικό πληθυσμό του ΔΣΧ και σχετιζόταν θετικά με την έκφραση της α3β1 ιντεγκρίνης και του C5b-9, αλλά και με τον αριθμό των PCNA (+) κυττάρων. Με βάση τα ευρήματα αυτά βασικό μηχανισμό στην πρόκληση της ίνωσης του ΔΣΧ αποτελεί η σπειραματοσκλήρυνση. Η επακόλουθη λευκωματουρία οδηγεί σε ενεργοποίηση των κυττάρων του ΔΣΧ. Στη συνέχεια τα μακροφάγα του ΔΣΧ παίζουν καθοριστικό ρόλο στην εξέλιξη της ίνωσης, είτε απευθείας, είτε έμμεσα, μέσω αλληλεπίδρασης με τις α3β1 ιντεγκρίνες και τους μυοϊνοβλάστες ή μέσω του C5b-9 και του TGF-βl. Άλλοι σπειραματικοί παράγοντες που ενισχύουν τους μηχανισμούς αυτούς είναι ενδεχομένως η α3β1 ιντεγκρίνη και το C5b-9 μέσω ενεργοποίησης των κυττάρων του ΔΣΧ και κυρίως των μακροφάγων. Η σημασία των ευρημάτων ενισχύεται από το γεγονός ότι ο βαθμός έκπτωσης νεφρικής λειτουργίας κατά τη διάγνωση της νόσου, παρουσίαζε υψηλή συσχέτιση τόσο με τη βαρύτητα της σπειραματοσκλήρυνσης όσο και με την έκταση της διήθησης του ΔΣΧ από μακροφάγα. Στο δεύτερο μέρος της μελέτης εκτιμήθηκε η επίδραση της αγωγής με ω3-λιπαρά οξέα στην εξέλιξη της νόσου. Στην προοπτική τυχαιοποιημένη αυτή μελέτη 42 ασθενείς με τη νόσο ταξινομήθηκαν τυχαία σε δύο ομάδες. Στην ομάδα Α (20 ασθενείς) χορηγήθηκαν ω3-λιπαρά οξέα, ενώ η ομάδα Β (22 ασθενείς) ακολούθησε συμπτωματική αντιμετώπιση. Μεταξύ των ασθενών των δύο ομάδων δεν υπήρχαν διαφορές ως προς τα κλινικά, βιοχημικά, ιστολογικά και ανοσοϊστοχημικά ευρήματα. Η διάρκεια της περιόδου θεραπείας ήταν 59±29 (14-119) μήνες. Στο τέλος της παρακολούθησης, στην ομάδα Α η βαρύτητα της λευκωματουρίας παρουσίασε σημαντική μείωση, ενώ ο ρυθμός σπειραματικής διήθησης (ΡΣΔ) παρουσίασε μικρή αλλά μη σημαντική αύξηση. Στην ομάδα Β ο βαθμός της λευκωματουρίας δεν μεταβλήθηκε σημαντικά, ενώ παρατηρήθηκε πτώση στο ΡΣΔ. Η επίδραση των αΜΕΑ ελέγχθηκε αναδρομικά και διαπιστώθηκε ότι η χορήγηση μόνο αΜΕΑ δεν επηρέαζε σημαντικά τη λευκωματουρία ούτε επιδρούσε στην εξέλιξη της νεφρικής βλάβης. Η χορήγηση ω3-λιπαρών οξέων ως μονοθεραπεία είχε ευνοϊκή δράση στη νεφρική λειτουργία, χωρίς σημαντική ύφεση της λευκωματουρίας. Η σύγχρονη χορήγηση αΜΕΑ και ω3-λιπαρών οξέων είχε τα καλύτερα αποτελέσματα τόσο στην αύξηση του ΡΣΔ, όσο και στην ελάττωση της λευκωματουρίας. Η κρεατινίνη του ορού στο τέλος της παρακολούθησης στην ομάδα Β εξακολουθούσε να σχετίζεται με την έκταση της σπειραματοσκλήρυνσης, τη βαρύτητα της ίνωσης του ΔΣΧ και την διάμεσο-σωληναριακή έκφραση του TGF-βl κατά τη διάγνωση της νόσου. Στην ομάδα Α οι συσχετίσεις αυτές είχαν εξαλειφθεί στο τέλος της περιόδου παρακολούθησης, γεγονός που μπορεί να σημαίνει ότι τα ω3-λιπαρά οξέα εξασκούσαν τα ευνοϊκά τους αποτελέσματα μέσω της ανασταλτικής τους δράσης στον TGF-βl ο οποίος παίζει σημαντικό ρόλο στη διαδικασία της σκλήρυνσης στο νεφρικό ιστό

Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors

Microbiome in Chronic Kidney Disease

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human’s body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD

COVID-19 Infection and Response to Vaccination in Chronic Kidney Disease and Renal Transplantation: A Brief Presentation

Chronic kidney disease (CKD) is associated with phenotypic and functional changes in the immune system, followed by detrimental clinical consequences, such as severe infections and defective response to vaccination. Two years of the pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have undoubtedly changed the world; however, all efforts to confront infection and provide new generation vaccines tremendously improved our understanding of the mechanisms of the immune response against infections and after vaccination. Humoral and cellular responses to vaccines, including mRNA vaccines, are apparently affected in CKD patients, as elimination of recent thymic emigrant and naïve lymphocytes and regulatory T-cells, together with contraction of T-cell repertoire and homeostatic proliferation rate, which characterized CKD patients are responsible for impaired immune activation. Successful renal transplantation will restore some of these changes, although several epigenetic changes are irreversible and even accelerated by the induction of immunosuppression. Response to vaccination is definitely impaired among both CKD and RT patients. In the present review, we analyzed the differences in immune response after vaccination between these patients and healthy individuals and depicted specific parameters, such as alterations in the immune system, predisposing to this deficient response

Type of ANCA May Be Indispensable in Distinguishing Subphenotypes of Different Clinical Entities in ANCA-Associated Vasculitis

The traditional nomenclature system for classifying antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) based on clinical phenotype describes granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and everyday clinical practice; yet, a substantial overlap in clinical presentation still exists and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative) could be more accurate and also closer to the nature of the disease compared to the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV in terms of epidemiology, pathogenesis, histological and clinical manifestations and response to therapeutic approaches

Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients

SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we present two dialysis patients with no previous history of thyroid disease who developed immune mediated thyroid disorders after BNT162b mRNA vaccine against SARS-CoV-2. The first patient is a 29-year-old man on hemodialysis diagnosed with Grave’s disease four months post-vaccination and the second one is a 67-year-old female on peritoneal dialysis who developed Hashimoto’s thyroiditis two months post-vaccination. Grave’s disease is uncommon in dialysis patients, whereas Hashimoto’s thyroiditis has a higher incidence in this population. Time proximity in both cases suggests potential causality. To our knowledge, this is the first report of de novo immune-mediated thyroid disorders in dialysis patients following vaccination against SARS-CoV-2

Circulating anti-phospholipase A2 receptor antibodies as a diagnostic and prognostic marker in Greek patients with idiopathic membranous nephropathy – a retrospective cohort study

Introduction. Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy

ANCA-Associated Vasculitis May Result as a Complication to Both SARS-CoV-2 Infection and Vaccination

In the last two years, our world experienced one of the most devastating and fast-exploding pandemic, due to the wide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The scientific community managed to develop effective vaccines, the main weapons to shield the immune system and protect people. Nevertheless, both SARS-CoV-2 infection and the vaccination against it have been associated with the stimulation of inflammatory cells such as T and B lymphocytes that results in a cytokine storm, endothelial inflammation and vascular injury, which can lead to different types of vasculitis. We present the first case of de novo MPO-ANCA-associated vasculitis, which developed shortly after SARS-CoV-2 vaccination, adequately responded to treatment, and subsequently relapsed after COVID-19 infection. With this case, we indicate an etiological connection between viral infection and disease development, as well as the possibility of a common immune mechanism between SARS-CoV-2 infection and vaccination, that can stimulate vascular events and lead to vasculitis. There have been several case reports of de novo vasculitis, affecting large, medium, or small vessels, following either infection or vaccination against COVID-19, during the pandemic outbreak. We summarize previous reports and also analyze proposed pathogenic mechanisms between SARS-CoV-2 and vasculitis

Evaluation of Subclinical Vascular Disease in Diabetic Kidney Disease: A Tool for Personalization of Management of a High-Risk Population

Background: Patients with diabetic kidney disease (DKD) are at increased risk for cardiovascular events but traditional risk factors do not fully explain this association. Evaluation of subclinical vascular disease might improve risk stratification and management of these patients. The aim of the study was to compare the prevalence of markers of arterial stiffness, carotid atherosclerosis and peripheral arterial disease between patients with DKD and patients with type 2 diabetes mellitus (T2DM) and preserved kidney function. Methods: We prospectively enrolled patients with DKD and age- and gender-matched patients with T2DM but without DKD (estimated glomerular filtration rate < and ≥60 mL/min/1.73 m2, respectively). The presence of arterial stiffness was evaluated by measuring pulse wave velocity (PWV), augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (AIx@75) and central systolic, diastolic, pulse and mean blood pressure. The presence of carotid atherosclerosis was evaluated by measuring carotid stenosis, carotid intima-media thickness and maximal plaque thickness. The presence of PAD was evaluated with the measurement of ankle-brachial index (ABI). Results: Forty patients with T2DM were included in the study (mean age 71.6 ± 8.9 years). The prevalence of cardiovascular risk factors was similar in patients with and without DKD. PWV was higher in the former (9.8 ± 5.5 and 6.6 ± 4.4 m/s, respectively; p < 0.05) and carotid stenosis of the left carotid artery was also greater in patients with DKD (36.5 ± 12.6 and 22.1 ± 17.2%, respectively; p < 0.05). Other markers of arterial stiffness and carotid atherosclerosis and ABI did not differ between patients with DKD and those without DKD. Conclusions: Patients with DKD appear to have more pronounced arterial stiffness and carotid atherosclerosis than patients with T2DM and preserved kidney function despite the similar prevalence of traditional cardiovascular risk factors in the two groups. Therefore, evaluating the presence of subclinical vascular disease in these patients could be a useful tool for the personalization of their management