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Only fifteen months after the beginning of the COVID-19 pandemic, several vaccines are already available for clinical use. While the spike protein of SARS-CoV-2 constitutes the main target of all predominant SARS-CoV-2 vaccines, they work by different mechanisms (mRNA-based vaccines vs. vector-based vaccines vs. protein-based vaccines).Though there are slight differences regarding the level of protection against mild COVID-19, all five vaccines that have been through phase 3 trials were nearly 100 % effective in preventing severe or fatal cases of COVID-19. The side effects were of short duration.Patients with chronic kidney disease (or other significant comorbidities) were largely excluded from Phase 3 trials, which makes definite recommendations concerning their vaccination difficult. The vaccine's effectiveness may be reduced in that population due to a uremic immune defect and/or immunosuppressive medication. However, these patients have an increased risk for severe or fatal COVID-19, so that they may particularly benefit from the vaccine. Innerhalb von nur 15 Monaten nach Beginn der COVID-19-Pandemie stehen bereits mehrere SARS-CoV-2-Impfstoffe zum klinischen Einsatz bereit. Während das Zielmolekül aller prädominierenden Vakzine das Spike-Protein von SARS-CoV-2 ist, lassen sie sich anhand ihres Wirkprinzip in mRNA-basierte, Vektor-basierte und Protein-basierte Impfstoffe unterscheiden. BEDEUTUNG FüR CHRONISCH NIERENKRANKE MENSCHEN: Das Aussprechen von Empfehlungen für chronisch nierenkranke Menschen ist aufgrund deren geringer Repräsentation in den Zulassungsstudien erschwert – wie bei anderen Patienten mit schwerer Komorbidität. Aufgrund von urämischem Immundefekt und/oder medikamentöser Immunsuppression könnte die Effektivität der Impfung im Einzelfall relativ vermindert sein. Dennoch profitieren vermutlich gerade diese Patienten von einer Impfung, da sie ein erhöhtes Risiko für einen schweren oder gar tödlichen COVID-19-Verlauf aufweisen.

IgG4-related disease (IgG4-RD) is an entity first described less than 20 years ago, characterized by tumorous swelling of affected organs. Differentiation from malignant disease, systemic infections and other systemic autoimmune diseases can be challenging. Typical histopathologic findings facilitate a diagnosis in a compatible clinical context. Because nearly every organ system can be affected, management of IgG4-RD is a challenging task requiring multidisciplinary work-up and treatment. Medical treatment usually consists of glucocorticoids, which may be combined with other immunosuppressives. Surgical or interventional treatment may be necessary if complications arise. Since high-quality evidence is lacking for most aspects of the management of IgG4-RD, international collaborative studies are urgently needed.ÜBERSICHT UND NOMENKLATUR: Die IgG4-assoziierte Erkrankung (IgG4-RD) ist eine erst kürzlich beschriebene heterogene Krankheitsentität, der viele vorher als eigenständige Einzelorganerkrankungen interpretierte Manifestationen zugerechnet werden. Hauptsymptom ist die Schwellung oder Vergrößerung betroffener Organe.Die Diagnose wird in Zusammenschau von Anamnese, klinischem Bild, Bildgebung, Histopathologie und IgG4-spezifischen Tests in Labor und Histologie gestellt.Häufige Laborbefunde sind: erhöhtes Serum-IgG4, IgE und CRP, Hypergammaglobulinämie, Hypokomplementämie und Eosinophilie.Das typische Bild umfasst folgende Hauptcharakteristika: dichte lymphoplasmazelluläre Infiltrate, storiforme Fibrose und obliterative Phlebitis. Ferner treten vermehrte IgG4-positive Plasmazellen auf.Diverse andere Krankheitsbilder können die IgG4-RD imitieren. MEDIKAMENTöSE THERAPIE: Neu sind eine Studie zu Mycophenolat-Mofetil und Daten zu Rituximab bei sonst weitgehend fehlender Evidenz aus Studien zur Behandlung der IgG4-RD.Glukokortikoide (GC) sind die Grundlage der medikamentösen Therapie.Es herrscht weiterhin kein Konsens, ob konventionelle Immunsuppressiva als GC-sparende Therapie immer oder nur in besonderen Fällen Teil der medikamentösen Therapie sein sollten.Rituximab ist eine etablierte Reservetherapie.Mechanische Obstruktionen und Kompressionen können chirurgische und interventionelle Verfahren notwendig machen.

Due to a high rate of cardiovascular events and the high-incidence of atrial fibrillation, many patients with chronic kidney disease (CKD) need to be anticoagulated and/or be subjected to anti platelet therapy (APT). As most studies historically excluded patients with CKD and a creatinine-clearance below 30 ml/min, guidelines for this patient group are only slowly being renewed depending on emerging study data.In patients with CKD stage 1-3, any non-vitamin K dependent oral anticoagulant (NOAC) should be preferentially used over vitamin K antagonists (VKA). In CKD stage 4, dabigatran should be avoided.The decision to anticoagulate a maintenance dialysis patient with atrial fibrillation has to be made on an individual basis considering their thrombosis and bleeding risk. Currently, in Europe all oral anticoagulants can be used only on an off-label basis in these patients. Randomized controlled trials investigating the efficacy and safety of apixaban versus VKA are currently underway. Alternative treatment options (e. g. left appendage occlusion) should be considered.Study data on APT in moderate to advanced CKD are similarly scarce. Despite APT not being renally eliminated, bleeding risk is increased due to uremic platelet dysfunction. When combining APT with NOAC, dose reduction of the latter needs to be addressed.ORALE ANTIKOAGULATION BEI NICHT DIALYSEPFLICHTIGER CHRONISCHER NIERENKRANKHEIT: In großen Zulassungsstudien haben sich die Nicht-Vitamin-K-abhängigen oralen Antikoagulanzien (NOAK) bei Patienten mit nicht valvulärem Vorhofflimmern als mindestens so effektiv in der Verhinderung thromboembolischer Ereignisse gezeigt wie Vitamin-K-Antagonisten (VKA). Die NOAK zeigen generell eine geringere Neigung zu schweren, lebensbedrohlichen Blutungen als die VKA. In den Zulassungsstudien wurden Patienten mit einer Kreatinin-Clearance von kleiner 30 ml/min meist nicht inkludiert, sodass für Patienten mit einer Kreatinin-Clearance von 15–30 ml/min zwar für Rivaroxaban, Apixaban und Edoxaban eine Zulassung besteht, die Datenlage zur Effektivität und Sicherheit jedoch nicht so fundiert ist wie bei Patienten mit einer Kreatinin-Clearance von 30 ml/min. ANTIKOAGULATION BEI TERMINALER NIERENINSUFFIZIENZ: Die Indikation zur Antikoagulation muss bei chronischen Dialysepatienten mit Vorhofflimmern derzeit weiterhin individualisiert gestellt werden. Es ist in diesem Kollektiv unklar, ob dialysepflichtige VHF-Patienten überhaupt von einer oralen Antikoagulation profitieren und welches hierfür eine sichere und effektive Substanz ist: Randomisiert-kontrollierte Studien zu Apixaban versus VKA werden klären, ob NOAK eine sichere und effiziente Therapiestrategie bei diesem Patientenkollektiv sind (RENAL-AF, AXADIA). THROMBOZYTENAGGREGATIONSHEMMUNG BEI CHRONISCHER NIERENKRANKHEIT: Generell sollten Patienten auch mit schwerer CKD oder Dialysepflichtigkeit die Thrombozytenaggregationshemmung nach kardiologischer Leitlinienempfehlung erhalten. Auf dem Boden des erhöhten Blutungsrisikos in diesem Kollektiv erscheinen moderne Kombinationen aus NOAK und einer einzelnen TAH-Substanz, die das alte „Triple-Regime“, bestehend aus doppelter TAH plus VKA ersetzen, besonders interessant.

Heart rate is an easily accessible clinical variable with wide-ranging prognostic impact. Elevated resting heart rate predicts an elevated cardiovascular risk. Epidemiological studies demonstrate a relevant association between heart rate and survival in individuals without diagnosed cardiovascular disease and with cardiovascular disease like hypertension, coronary artery disease (CAD) and heart failure. Whereas a goal directed pharmacological heart rate reduction is not supported by clinical evidence for primary prevention it plays a prognostic role for patients with CAD and chronic heart failure. Moreover heart rate can be characterized as an independent risk factor for patients with heart failure and potentially for those with CAD. As a result the common guidelines recommend heart rate reduction as a target of therapy.

Use of the ADP (P2Y(12))-receptor antagonist clopidogrel is a cornerstone of dual platelet inhibition in acute coronary syndromes and following stent implantation. Because of the metabolization into its active form and the irreversible inhibition of the ADP receptor there are disadvantages to clopidogrel which could limit its efficacy in reducing clinical events. This is particularly problematic in so-called poor responders with reduced metabolizing activity and hence reduced platelet inhibition. Two novel drugs for platelet inhibition in acute coronary syndrome could become relevant in clinical practice. The irreversible ADP-receptor antagonist prasugrel led to stronger platelet inhibition, fewer ischemic events but more bleeding complications compared to clopidogrel in the TRITON-TIMI-38 trial. The reversibly binding, direct-acting ADP-receptor antagonist ticagrelor, which is effective without metabolization, is also superior over clopidogrel in reducing platelet aggregation and decreased the number of ischemic events in the PLATO-trial. However, it did not increase the rate of overall major bleeding and was shown to reduce total mortality. This review article summarizes current data on novel platelet inhibitors and delineates their potential influence on clinical practice.

The most frequent cardiac arrhythmia and main cause for cardio-embolic stroke is atrial fibrillation. Prophylaxis for thrombembolic events is performed regarding individual risk of patients with either ASS or vitamin-K-antagonists. Efficacy and safety of oral anticoagulation is limited by a narrow therapeutical range as well as by inter- and intraindividual variability of INR-values due to genetic disposition, differences in alimentation, dosage errors, rare control of INR-levels and drug-interactions. New oral anticoagulants with different mechanisms of action may be a promising therapeutic option in future. This review addresses the new anticoagulants Apixaban, Rivaroxban and Dabigatranetexilat with the design and as available the results of the corresponding phase-III-trials in atrial fibrillation (ARISTOTLE, ROCKET-AF, RE-LY).

The stimulation of collateral artery growth (arteriogenesis) is a promising alternative approach to non-invasively treat arterial obstructive disease, such as coronary, peripheral or cerebral artery disease. Patients unable to undergo conventional revascularization strategies may benefit from adaptive arteriogenesis. Underlying mechanisms are experimentally validated and include an increase in shear stress after obstruction or occlusion of a major artery; monocyte adhesion, transmigration and perivascular accumulation, secretion of growth factors; and smooth muscle and endothelial cell proliferation and growth of pre-existent collateral arteries. Therapeutic stimulation of arteriogenesis with cytokines has been successfully performed in experimental models. Translation into clinical practice, however, has hitherto been problematic. Reasons for this include differences between the healthy laboratory animal and an often severely diseased patient, possible harmful effects of pro-arteriogenic therapies and unsuitable clinical endpoints for the detection of collateral artery growth. Recent investigations of human arteriogenesis demonstrate significant inter-individual differences and point towards the importance of anti-arteriogenic mechanisms in patients with impaired adaptive arteriogenesis and high cardiovascular risk factors.