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Aortic stenosis (AS) is a progressive and degenerative disease that necessitates valve replacement through either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). Various studies have shown that, unlike for TAVR, SAVR is associated with an elevated risk for women as compared to men. The aim of this review is to better understand the risks and their possible causes, associated with the use of both TAVR and SAVR in female patients. Our systematic review included studies published between 2012 and 2020, identified through specific searches of PubMed. Compatibility of publications, determined by the use of pre-defined inclusion/exclusion criteria, resulted in 15 articles being used in our review. Overall, more men than women undergo SAVR, but our findings confirmed that SAVR is associated with worse outcomes in women in the short-term. Reasons for a higher 30-day mortality post-SAVR in women include an increased age, higher in-hospital mortality and, possibly baseline comorbidities and anatomical differences. There was no difference observed in 30-day mortality between men and women undergoing TAVR. Female patients appear to have a better longer-term survival post-TAVR than their male counterparts. Understanding the reasons why women have worse outcomes post-SAVR is essential for ensuring appropriate treatment selection for patients with AS, as well as for achieving the best possible long-term and safety outcomes for these patients.

Detection of renal artery stenosis (RAS) using Doppler is difficult to evaluate, particularly under conditions such as bilateral RAS or difficultly accessible renal arteries (RA). The objective of the present study was to assess the utility of splenic arterial compared to renal flow as an additional parameter in the Doppler evaluation of RAS. The difference between the resistive indices (RI) determined in renal and splenic parenchymal arteries (ΔRI(K−S)) was evaluated in 181 hypertensive subjects without any evidence of RAS. Subsequently 47 RA in 24 patients with suspected RAS were angiographically assessed. A ΔRI(K−S) of 0.055 (median) was determined in the population without any evidence of RAS similar to RA with angiographically excluded stenosis (ΔRI(K−S) 0.068). In contrast, in angiographic proven RAS, ΔRI(K−S) was significantly lower (−0.050; P

Background: Microhematuria (MH) is a symptom frequently leading to uncertainty as to when a nephrology referral is appropriate. Because MH may be indicative of severe kidney disorders, prompt diagnosis and potential treatment initiation can be important. We aimed to identify further variables that point at a nephrological cause, in particular of glomerulonephritis (GN), when MH is diagnosed. Methods: A retrospective analysis of data acquired from patients attending a nephrology office due to MH was performed. Demographic information and diagnostic tests were evaluated in order to identify factors that were associated with a nephrological cause. Results: Patients with MH (n = 805) as indicated by a urine stick analysis were included. Of these, MH was confirmed by urine sediment analysis in 543 patients (67.5%). Of those, 48.3% had a nephrological cause, including 12.4% with GN and 2.9% with rapid progressive GN (RPGN). A urine dipstick finding of ≥ 250 erythrocytes per microliter, microalbuminuria and elevated leukocytes increased the probability of having a GN to 62.4%. Furthermore, the presence of microalbuminuria, GFR < 60 mL/min, history of hypertension and diabetes mellitus increased the probability for all nephrological causes to 95.4%. Conclusion: There are a number of factors available that help to assess the need for a nephrology referral in patients with microhematuria. J Clin Med Res. 2017;9(7):560-566 doi: https://doi.org/10.14740/jocmr2993w

ObjectiveThrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up.MethodsIn this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed.ResultsAmong the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis (PConclusionsTRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion.

Background: Bone morphogenetic protein-5 (BMP-5) has been shown to be essential for nephrogenesis. Its role in adult kidney and in patients with hypertensive nephrosclerosis is still unknown. Methods: BMP-5 expression was evaluated by immunostaining and real-time PCR in tissue samples from normal and nephrosclerotic human kidneys. The impact of transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) and angiotensin-II (AT-II) on expression of BMP-5 and its receptors was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-5 were evaluated by testing its influence on TGF-β–induced epithelial-to-mesenchymal transition (EMT), TNF-α–induced apoptosis of HK-2 cells and inflammatory cell infiltration. Results: BMP-5 expression was localized in tubular epithelial cells and significantly decreased in nephrosclerotic kidneys. Stimulation of HK-2 cells with TGF-β, TNF-α and AT-II resulted in a significant decreased expression of BMP-5 and its receptors. BMP-5 attenuated TGF-β–induced EMT, TNF-α–induced apoptosis and migration of mononuclear cells. Conclusions: BMP-5 is expressed in the tubuli of adult kidneys. Its decreased expression in nephrosclerosis along with its regenerative capabilities in HK-2 cells may point to a protective role in hypertensive nephrosclerosis.

Background and aims Arterial hypertension is a major cause of death worldwide. For the most part, treatment for hypertension can be performed on an outpatient basis. However, some patients also require inpatient treatment, and the contributing factors for this remain unknown. Therefore, the primary objective of the present study was to determine which patient characteristics are associated with inpatient treatment for arterial hypertension. Methods Here, we conducted a mono-centric study of 103 hypertensive subjects, who were treated as inpatients in the Department of Nephrology and rheumatology of the university medical faculty of Göttingen. Therapies were not altered, and data collection was performed retrospectively. In addition to epidemiological information, the following data were recorded: patient symptoms, blood pressure (BP), anti-hypertensive therapy, and concomitant diseases (e.g., renal and cardiovascular conditions). Results Approximately half (53 %) of all subjects treated on an inpatient basis displayed elevated BP (>140/90 mmHg), while the remaining 47 % of patients showed normotensive readings (

Der Anteil ubergewichtiger und adiposer Patienten in der Bevolkerung steigt seit Jahren kontinuierlich an und liegt mittlerweile bei etwa 60%. Betroffen sind nicht mehr nur Erwachsene, sondern haufig auch schon Jugendliche und Kinder. Kennzeichnend fur adipose Patienten ist das haufige Auftreten von metabolischen Risikofaktoren. Die Konsequenz ist eine Vielfalt an direkten (z. B. Bluthochdruck) und indirekten Folgeerkrankungen (z. B. Herzrhythmusstorungen), die haufig zu einer reduzierten Lebenserwartung und -qualitat fur ubergewichtige und adipose im Vergleich zu normalgewichtigen Patienten fuhrt. Modifikationen des Lebensstils fuhren nur selten zur Gewichtsreduktion und der Senkung des kardiovaskularen Risikos. Daher wird eine medikamentose Pravention von Folgeerkrankungen in Erwagung gezogen. Eine gezielte Senkung des haufig erhohten Blutdruckes, eine Therapie einer evtl. vorliegenden Hyperlipidamie und eine Thrombozytenaggregationshemmung sind Masnahmen, die zu einer deutlichen Reduktion des kardiovaskularen Risikos bei adiposen Patienten fuhren.

BACKGROUND: The chemokine/chemokine receptor pair CX(3)C-L/CX(3)C-R is suspected to play a role in renal fibrogenesis. The aim of this study was to investigate their function in an animal model of slowly progressive chronic renal failure. METHODS: Functional data were analysed in folic acid nephropathy (FAN) at different time points (up to day 142 after induction). Immunostaining for CX(3)C-L, CD3, S100A4, collagen type I, fibronectin, alpha-smooth muscle actin, Tamm-horsfall protein, aquaporin 1 and 2 as well as quantitative real-time PCR (qRT-PCR) for CX(3)C-L, CX(3)C-R and fibroblast-specific protein 1 (FSP-1) were performed. Additionally, regulatory mechanisms and functional activity of CX(3)C-L in murine proximal and distal tubular epithelial cells as well as in fibroblasts were investigated. RESULTS: CX(3)C-L/GAPDH ratio was upregulated in FAN 3.4-fold at day 7 further increasing up to 7.1-fold at day 106. The expression of mRNA CX(3)C-L correlated well with CX(3)C-R (R(2) = 0.96), the number of infiltrating CD3+ cells (R(2) = 0.60) and the degree of tubulointerstitial fibrosis (R(2) = 0.56) and moderately with FSP-1 (R(2) = 0.33). Interleukin-1beta, tumour necrosis factor-alpha, transforming growth factor-beta as well as the reactive oxygen species (ROS) H(2)O(2) were identified by qRT-PCR as inductors of CX(3)C-L/fractalkine (FKN) in tubular epithelial cells. Functionally, CX(3)C-L/FKN chemoattracts peripheral blood mononuclear cells, activates several aspects of fibrogenesis and induces the mitogen-activated protein kinases in renal fibroblasts. CONCLUSIONS: In FAN, there is a good correlation between the expression of CX(3)C-L with markers of interstitial inflammation and fibrosis which may result from upregulation by pro-inflammatory and pro-fibrotic cytokines as well as by ROS in tubular epithelial cells. The FKN system may promote renal inflammation and renal fibrogenesis.

Background Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT), expression of TGF-β receptor type I (TGF-βRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-α induced apoptosis of proximal tubular cells. Results BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2. Conclusions The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.

Abstract 3800 Introduction: In an ongoing diagnostic study we are currently following chromosomal anomalies in immunomagnetically enriched CD34+ peripheral blood cells in patients with suspected or proven myelodysplastic syndromes (MDS) at short intervals using fluorescence in situ hybridization (FISH) analysis every two to three months over three years. A loss of the Y chromosome was detected in 4% of these patients, as a single anomaly in 2%. Since it is controversially discussed whether loss of the Y chromosome is an age-related or a clonal event in patients with MDS, we aimed to examine whether a Y-loss is clonal or an age-related event in our patients. Methods: For patients with known Y-loss, we used peripheral blood not only to immunomagnetically enrich clonal CD34+ cells, but also CD3+ T-cells not belonging to the MDS clone. Subsequently, we performed FISH analysis to compare the clone sizes of cells with Y-loss in CD34+ and CD3+ cells. As our laboratory threshold for the FISH probe in CD34+ peripheral blood cells is 5%, we included 18 patients with clone sizes exceeding this threshold in CD34+ cells. The median age of the patients was 76 years (range 62–89). To establish a laboratory threshold for the FISH probe in CD3+ peripheral blood cells, we analyzed T-cells of 25 healthy men with a median age of 27 years (range 19–35). Furthermore, we just initialized an investigation of the laboratory threshold for the FISH probe in CD3+ peripheral blood cells of elder men by measuring the frequency of loss of the Y chromosome in T-cells of this control cohort not suffering from hematopoietic diseases. Until now we could recruit 15 men with a median age of 75 years (range 66–84) for this purpose, further will follow soon. Results: In patients with suspected or proven MDS, the number of cells with -Y was significantly increased in CD34+ cells compared to CD3+ cells (p Conclusion: Regarding the absence of Y-loss in CD3+ peripheral blood cells of young healthy men compared to up to 14% -Y in CD3+ peripheral blood cells of elder men, the low proportion of -Y in CD3+ cells of our patients suggests an age related Y-loss in normal T-cells. As the number of CD34+ peripheral blood cells with -Y exceeds the number of CD3+ peripheral blood cells with -Y in all patients, we assume that Y-loss is clonal to some extent in all of them. We established a reliable method to test if loss of the Y chromosome is disease- or age-related in individual MDS patients. It can be used to determine a clonal disease in patients with suspected MDS and Y-loss as sole abnormality. Disclosures: No relevant conflicts of interest to declare.

Bone morphogenetic proteins (BMPs) have been identified as important morphogens with pleiotropic functions in regulating the development, homeostasis and repair of various tissues. The aim of this study was to characterize the expression of BMPs in synovial tissues under normal and arthritic conditions. Synovial tissue from normal donors (ND) and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were analyzed for BMP expression by using microarray hybridization. Differential expression of BMP-4 and BMP-5 was validated by semiquantitative RT-PCR, in situ hybridization and immunohistochemistry. Activity of arthritis was determined by routine parameters for systemic inflammation, by histological scoring of synovitis and by semiquantitative RT-PCR of IL-1β, TNF-α, stromelysin and collagenase I in synovial tissue. Expression of BMP-4 and BMP-5 mRNA was found to be significantly decreased in synovial tissue of patients with RA in comparison with ND by microarray analysis (p < 0.0083 and p < 0.0091). Validation by PCR confirmed these data in RA (p < 0.002) and also revealed a significant decrease in BMP-4 and BMP-5 expression in OA compared with ND (p < 0.015). Furthermore, histomorphological distribution of both morphogens as determined by in situ hybridization and immunohistochemistry showed a dominance in the lining layer of normal tissues, whereas chronically inflamed tissue from patients with RA revealed BMP expression mainly scattered across deeper layers. In OA, these changes were less pronounced with variable distribution of BMPs in the lining and sublining layer. BMP-4 and BMP-5 are expressed in normal synovial tissue and were found decreased in OA and RA. This may suggest a role of distinct BMPs in joint homeostasis that is disturbed in inflammatory and degenerative joint diseases. In comparison with previous reports, these data underline the complex impact of these factors on homeostasis and remodeling in joint physiology and pathology.