Pulmorenale Interaktionen zeigen sich im klinischen Alltag am häufigsten in Form von pulmorenalen Autoimmunerkrankungen. Pulmorenale Syndrome sind selten vorkommende, potenziell schwer verlaufende, rapid-progressive Glomerulonephritiden auf dem Boden von autoimmunen Systemerkrankungen mit pulmonaler Beteiligung. Unbehandelt haben pulmorenale Syndrome eine hohe Morbidität und Mortalität. Daher ist die rechtzeitige Diagnose und Einleitung der effektiven Therapie eine vordringliche Aufgabe, um das klinische Outcome der Patienten nachhaltig zu verbessern.

Background. Hyperuricemia is not only associated with gout but also with hypertension, atherosclerosis and chronic kidney disease (CKD); however, in cases of disproportionally high serum uric acid levels without symptoms of gout and slowly progressive chronic kidney failure especially in young people, a genetic cause of hyperuricemia needs to be considered.Pathogenetic associations. The results of experimental studies suggest that hyperuricemia can be a pathophysiologically relevant cardiovascular risk factor. In animal studies hyperuricemia leads to oxidative stress and vascular dysfunction and chronically elevated uric acid levels can result in structural changes of the vessel wall. Epidemiological data show a connection between hyperuricemia and hypertension and uric acid lowering therapy has been shown to lower arterial blood pressure. In CKD, uric acid increases in parallel with the decline in GFR and an increase in proteinuria. Several ongoing prospective clinical trials will clarify if pharmacological lowering of uric acid will translate into reduction of relevant cardiovascular and renal endpoints.Therapy. The treatment of gout and the medicinal prophylaxis of further gout attacks depend on the comorbidities and especially CKD.

Hyperurikämie ist nicht nur mit Gicht, sondern auch mit arterieller Hypertonie, Atherosklerose und chronischer Niereninsuffizienz assoziiert. Bei langsam progredienter, asymptomatischer Niereninsuffizienz und unproportional erhöhtem Harnsäurespiegel v. a. im jungen Alter sollte an das Vorliegen einer genetisch bedingten Hyperurikämie denken lassen.

Arteriosclerotic renal artery stenosis (RAS) has an increased incidence in patients with cardiovascular risk factors. Clinically RAS presents in some patients as secondary, sometimes resistant arterial hypertension and in others as chronic renal insufficiency, sometimes with acute renal failure and in a third group both symptoms are observed. Doppler ultrasound plays a central role in the diagnosis of RAS. Therapeutically, it is important to identify hemodynamically relevant RAS before interventional therapy is initiated. The therapy of RAS has been under intensive debate since the publication of randomized controlled trials (RCT) which showed that only a subset of RAS can be successfully treated by interventional therapy. Since then the medicinal therapy of RAS has gained more and more impact. The following questions are raised: which forms of RAS can be treated by which therapy? What is the best medicinal therapy to treat RAS? What substances are recommended?.

Die arteriosklerotische Nierenarterienstenose (NAST) hat eine erhöhte Inzidenz bei Patienten mit kardiovaskulären Risikofaktoren. Klinisch präsentiert sich die NAST bei manchen Patienten als sekundäre, teils schwer einstellbare arterielle Hypertonie, bei anderen als chronische Niereninsuffizienz, teils mit akutem Nierenversagen; bei einer dritten Gruppe treten beide Symptome auf. In der Diagnostik der NAST kommt der farbcodierten Dopplersonographie eine zentrale Rolle zu. Therapeutisch muss eine hämodynamisch relevante NAST gesichert sein, bevor eine interventionelle Therapie angestrebt wird. Die Therapie der NAST ist seit dem Erscheinen von randomisierten, kontrollierten Studien (RCT) Gegenstand intensiver Diskussionen. Die RCT konnten zeigen, dass nur bestimmte NAST durch eine interventionelle Therapie erfolgreich behandelt werden. Seitdem gewinnt die medikamentöse Therapie mehr und mehr an Bedeutung. Es stellt sich daher die Frage, welcher Befund von welcher Therapie wann profitiert? Was ist die „richtige“ medikamentöse Therapie der NAST? Welche Substanzen werden empfohlen?

BACKGROUND AND PURPOSE ApolipoproteinE‐deficient [apoE (−/−)] mice, a model of human atherosclerosis, develop endothelial dysfunction caused by decreased levels of nitric oxide (NO). The endogenous peptide, angiotensin‐(1‐7) [Ang‐(1‐7)], acting through its specific GPCR, the Mas receptor, has endothelium‐dependent vasodilator properties. Here we have investigated if chronic treatment with Ang‐(1‐7) improved endothelial dysfunction in apoE (−/−) mice.EXPERIMENTAL APPROACH ApoE (−/−) mice fed on a lipid‐rich Western diet were divided into three groups and treated via osmotic minipumps with either saline, Ang‐(1‐7) (82 µg·kg−1·h−1) or the same dose of Ang‐(1‐7) together with D‐Ala‐Ang‐(1‐7) (125 µg·kg−1·h−1) for 6 weeks. Renal vascular function was assessed in isolated perfused kidneys.KEY RESULTS Ang‐(1‐7)‐treated apoE (−/−) mice showed improved renal endothelium‐dependent vasorelaxation induced by carbachol and increased renal basal cGMP production, compared with untreated apoE (−/−) mice. Tempol, a reactive oxygen species (ROS) scavenger, improved endothelium‐dependent vasorelaxation in kidneys of saline‐treated apoE (−/−) mice whereas no effect was observed in Ang‐(1‐7)‐treated mice. Chronic treatment with D‐Ala‐Ang‐(1‐7), a specific Mas receptor antagonist, abolished the beneficial effects of Ang‐(1‐7) on endothelium‐dependent vasorelaxation. Renal endothelium‐independent vasorelaxation showed no differences between treated and untreated mice. ROS production and expression levels of the NAD(P)H oxidase subunits gp91phox and p47phox were reduced in isolated preglomerular arterioles of Ang‐(1‐7)‐treated mice, compared with untreated mice, whereas eNOS expression was increased.CONCLUSION AND IMPLICATIONS Chronic infusion of Ang‐(1‐7) improved renal endothelial function via Mas receptors, in an experimental model of human cardiovascular disease, by increasing levels of endogenous NO.

Koenigshausen, E.; Ruetze, M.; Zierhut, U.; Potthoff, S. A.; Woznowski, M.; Stegbauer, J.; Quack, I.; Rump, L. C.; Sellin, L. Author Information

Potthoff, S. A.; Mori, Y.; Stegbauer, J.; Hoch, H.; Königshausen, E.; Woznowski, M.; Vonend, O.; Sellin, L.; Rump, L. C.; Quack, I. Author Information

Ciliary Neurotrophic factor (CNTF) is an interleukin-6-like (IL-6) cytokine which plays a distinct role in survival and differentiation of neuronal cells. Through binding to its own receptor and activation of the JAK2-STAT3-signaling cascade, CNTF mediates anti-inflammatory effects and reduces apoptosis. CNTF deficient mice show a detrimental progression of autoimmune encephalomyelitis. Despite the well examined role of CNTF in the central nervous system, its role in other tissues is poorly understood. AngiotensinII (angII) induces the expression of IL-6 by increased production of reactive oxygen species. Activation of the renin angiotensin system is a typical finding in chronic kidney disease. Due to the nature of CNTF and its receptor as an IL-6-like ligand and receptor, this study focuses on the role of CNTF in angII induced hypertension in uninephrectomized mice. One week after uninephrectomy, angII osmotic minipumps (1000ng/min/kgBW) were implanted in CNTF-KO (C57/Bl6J background) and matched C57/Bl6J male mice (WT) (n = 19). Blood pressure was measured via tail cuff for 2 weeks. In addition, kidneys from WT- and CNTF-KO-mice were isolate perfused and a dose-response relationship to angII was measured. WT- and CNTF-KO-mice developed hypertension within the first two days after surgery. Both groups showed an increase in systolic blood pressure (BP) over time. Comparison between the WT and CNTF-KO-group revealed that at any time point BP was significantly lower in the CNTF-KO-group compared to the WT-group (WT vs. CNTF-KO week1: 153 ± 3 vs. 139 ± 3 mmHg; week 2: 168 ± 4 mmHg vs. 151 ± 5 mmHg). Heart hypertrophy was significantly less in CNTF-KO (6.5 ± 0.4 mg/gBW) compared to the WT-mice (8.2 ± 0.6 mg/gBW). In the isolate perfused kidney, angII dependent pressure response was significantly lower in the CNTF-KO- compared to the WT-group. This study shows that CNTF plays an important role in BP response to angII. However, at present, it cannot be distinguished whether intra- or extracellular actions of CNTF are responsible for the differences in blood pressure regulation. Future studies are needed to elucidate the underlying mechanisms.