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Objective Aim of this study was to validate the Microlife BP B3 AFIB/enterprise resource planning (ERP) No: BP3KT1-3 N blood pressure (BP) monitor according to the American National Standards Institute (ANSI)/Association for the Advancement of Medical Instrumentation (AAMI)/International Organization for Standardization (ISO) 81060-2:2019 in adolescents and adults from a general population. Methods BP measurements on the upper arm were performed in 85 subjects (age range 12-88 years), using the Microlife BP B3 AFIB and a standard mercury reference sphygmomanometer. Results A total of 255 valid BP comparisons were performed for the present validation analysis. The mean ± SD difference between the test and the reference device was 0.70 ± 7.05 mmHg for SBP (pass criterion ≤5 mmHg) and -0.85 ± 4.70 mmHg for DBP (pass criterion ≤5 mmHg) with the SD below the required value of ≤8 mmHg. The mean ± SD of the intraindividual differences between the test and the reference device was 0.70 ± 5.87 mmHg for SBP (pass criterion for the SD ≤6.90 mmHg) and -0.85 ± 4.19 mmHg for DBP (pass criterion for the SD ≤6.88 mmHg). Conclusion The Microlife BP B3 AFIB/ERP No: BP3KT1-3 N has passed the criteria of the ANSI/AAMI/ISO 81060-2:2019 protocol and can be recommended for home BP measurements in adolescents and adults.

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

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

A wide variety of targeted therapies are available for the treatment of renal cancer that has progressed beyond the point at which surgery is a viable option. In addition, there are many more that are in the different stages of clinical trials. Here, we provide a methodical discussion of the efficacy and safety of targeted therapies for the treatment of advanced renal cell carcinoma. We conducted a systematic literature employing the search terms: renal cell carcinoma targets, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and each of the drugs discussed within these papers. The identified targeted therapies work by disrupting specific signalling pathways involved in tumour progression, such as those responsible for angiogenesis and cell proliferation. Tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are now established classes of drugs used in the treatment of renal cancer, with a total of six having received regulatory approval to date (sorafenib, sunitinib, pazopanib, axitinib, temsirolimus, and everolimus). Ongoing trials are likely to result in addition to these in the near future, for example, tivozanib, dovitinib, and cediranib. Furthermore, in addition to these small molecule drugs, immunotherapies involving monoclonal antibodies against signalling molecules such as vascular endothelial growth factor (bevacizumab) or programmed death-1 (nivolumab) are receiving increasing attention. Targeted therapies have great potential for disrupting tumour progression by inhibiting certain signalling pathways. As our understanding of the biochemical pathways involved in cancer progresses, additional targets are certain to become apparent, expanding treatment options even further.

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.

Lipoprotein apheresis (LA) is believed to exert anti-atherosclerotic effects beyond LDL-cholesterol reduction. We investigated 22 patients undergoing regular LA on a weekly basis (group A) before (AP) and after LA procedure (EP), 15 healthy individuals (group B), and 22 hyperlipoproteinemic patients with concomitant cardiovascular end organ damage treated without LA therapy (group C). Biomarkers of endothelial inflammation (hsCRP), plaque destabilization, and rupture (sVCAM, MMP-9, PAPP-A, ADMA) were quantified. Intergroup comparison revealed a statistically significant lower MMP-9 level in group A (AP and EP) compared with group C (P

The vast majority of patients with end-stage renal disease are treated with intermittent hemodialysis as a form of renal replacement therapy. To investigate the impact of hemodialysis membrane material on vital protein removal, dialysates from 26 well-characterized hemodialysis patients were collected 5 min after beginning, during 5h of treatment, as well as 5 min before ending of the dialysis sessions. Dialysis sessions were performed using either modified cellulose (n=12) (low-flux and high flux) or synthetic Polyflux (n=14) (low-flux and high-flux) dialyzer. Protein removal during hemodialysis was quantified and the dialysate proteome patterns were analyzed by 2-DE, MS and Western blot. There was a clear correlation between the type of membrane material and the amount of protein removed. Synthetic Polyflux membranes exhibit strong interaction with plasma proteins resulting in a significantly higher protein loss compared to modified cellulosic membrane. Moreover, the proteomics analysis showed that the removed proteins represented different molecular weight range and different functional groups: transport proteins, protease inhibitors, proteins with role in immune response and regulations, constructive proteins and as a part of HLA immune complex. The effect of this protein removal on hemodialysis treatment outcome should be investigated in further studies.

The most common immunosuppressive regimens after renal transplantation include calcineurin inhibitors (CNI). However, due to renal toxicity long-term graft survival does not seem to be positively affected by CNIs.In the present study, we investigated 17 patients, in which the CNI immunosuppression was converted to a CNI-free, mycophenolate sodium (MPS) regimen. Conversion was performed due to progressive impairment of the graft function from suspected CNI toxicity. We retrospectively analyzed graft function as well as toxicity and surrogate markers for 4 years before and 4 years after conversion using a repeated-measures mixed model data analysis and/or a paired sample t-test.The mean time point of therapy conversion was 11.2 ± 4.6 years after transplantation. Within 1 month of CNI discontinuation, allograft function improved significantly, remaining at a significant level for 2 years. The estimated glomerular filtration rate increased from 43.4 ± 14.8 to a maximum of 55.7 ± 21.7 mL/min at 1 year after conversion (P = .0027). After 4 years, the end of the observation period, renal function was similar to the baseline. There were no significant side effects.These data suggested that, when chronic CNI-toxicity is suspected, renal allograft recipients may benefit from CNI withdrawal in favor of a MPS-including immunosuppressive regimen.

The risk of infection in patients with rheumatic diseases is elevated, but a clear marker to differentiate the cause of the systemic inflammation is missing. We assessed the ability urinary immunoglobulin free light chains (FLCs) to indicate the presence of infection in patients with rheumatic disease. We performed a retrospective analysis of patients with rheumatic disease attending the Georg-August University Hospital in Goettingen, Germany, from January 2011 to December 2013. Subjects were included if they had urine levels of κ and λ FLCs available. A reference group of patients without autoimmune disease, but with documented infection, was constructed. A total of 1500 patients had their urinary FLCs quantified during the study period. Of the 382 patients with rheumatic disease, 172 (45%) displayed no systemic inflammation, 162 (42%) had inflammation due to the underlying disease activity, and 48 (13%) had inflammation due to a confirmed infection. Urinary FLC concentrations were much higher in patients with rheumatic diseases and infection (κ 68.8 ± 81.8 mg/L, λ 31.4 ± 53.5 mg/L) compared to those with inflammation due to rheumatic disease activity (κ 22.7 ± 26.3 mg/L, λ 8.1 ± 9.1 mg/L, κ p

Objectives Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is accompanied by increased cardiovascular (CV) risk. Treatment of AAV patients includes the management of conventional CV risk factors, primarily hypertension and hypercholesterolemia, while lipoprotein(a) (LP(a)) is an emerging potential target. Methods We performed a multicenter, retrospective study in Germany. Patients were considered if they were between 18 and 90 years old and presented with AAV. Patients with arterial hypertension but no autoimmune disease were used as a control group (HTN reference group). Results Compared to the reference group (n = 52), CV disease burden was significantly greater in patients with AAV (n = 53). Hypercholesterolemia was also more common in the AAV patients (71.7% vs 46.2% for the HTN; P = .008). Lipoprotein(a) levels were elevated in both groups, with 11.3% and 17.3% of the AAV and HTN groups, respectively, displaying a level above 0.6 g/l (P = .083). Guideline-recommended targets for low-density lipoprotein cholesterol and blood pressure levels were rarely met. According to Kidney Disease: Improving Global Outcomes guidelines, 72.5% of the patients with AAV should have been taking statins and/or ezetimibe for treatment of hyperlipidemia; however, only 24.3% of them were receiving such treatment. Blood pressure below ≤140/90 mmHg was reached in 78.6% of the patients with chronic kidney disease. However, for patients with chronic kidney disease and an albumin excretion rate of >30 mg/day, the recommended blood pressure is ≤130/80 mmHg, a value that was not reached in 65% of the AAV patients. Conclusion Patients with AAV are at high CV risk, but management of the associated risk factors is poor. In addition to improving the treatment of hypercholesterolemia and hypertension, lipoprotein(a) is a further potential target for reducing CV risk in individuals with AAV.

In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p

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 (

Depending on the individual definition of acute renal failure, its prevalence in intensive care units approaches 5-25 % of the cases under treatment and is associated with a definitely reduced survival rate. Hence, prevention of acute renal failure should always rank first. However, if renal replacement is nevertheless inevitable, we must definitely decide between a permanent and an intermittent procedure on the one hand and between hemodialysis and hemofiltration on the other. „Sustained low efficiency dialysis“ (SLED) during 8-12 hours is a good alternative combining the advantages of hemodialysis and continuous treatment. Hemodynamically unstable as well as definitely hyper-hydrated patients or patients suffering from hepatic insufficiency or increased intracranial pressure (e. g. skull and brain trauma) will improve in case of acute electrolytic disorders such as hyperkalemias, intoxications, hemorrhagic diathesis or in the mobilization phase. Intensive care specialists and nephrologists should individually decide which procedure would be preferable. The present article aims at assisting them.

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.

We retrospectively analyzed 10 906 lipid apheresis sessions (heparin-induced lipoprotein precipitation, direct adsorption of lipoproteins, double filtration plasmapheresis, dextran sulfate adsorption, and immunoadsorption) in 38 patients who were consecutively treated in our department during the last 20 years. The incidences of major cardiovascular events (MACE) (death, cerebrovascular accident, myocardial infarction, limb amputation, and renal vascular involvement) were taken separately as primary end-points or as a combined end-point. The time-course of secondary end-points (coronary and extracranial status of arteries, left ventricular function, occlusive artery disease, and calculated glomerular filtration rate [cGFR]) were also evaluated, as well as the extent of the reduction in plasma lipids and lipoproteins and the incidence of therapy associated side-effects. MACE decreased from 7.02% events per patient per year at the start of lipid apheresis to 1.17% during lipid apheresis and the rate of myocardial revascularization decreased from 22.8% to 3.8% per patient per year. Classical (diabetes mellitus, arterial hypertension, and smoking history), as well as novel risk factors (cGFR < 60 mL/min, statin withdrawal, mixed hyperlipoproteinemia, and elevated lipoprotein (a)) were associated with an elevated risk for MACE. All applied methods had comparable effects. All lipid apheresis methods proved to be safe and suitable for long-term treatment. The present data demonstrate that treatment with lipid apheresis is very effective and leads to long-term reduction in cardiovascular mortality and morbidity.

The occurrence of microalbuminuria or albuminuria indicates a disturbance of the barrier function of endothelial cells, basement membrane or of a structural-renal disease (including diseased podocytes). The prevalence of microalbuminuria in the general population is about 8 %, however, in high risk groups, prevalence rates of 50 % and more have been observed. Its incidence is strongly associated with increased cardiovascular morbidity and mortality. Blood pressure control and the blockade of the renin-angiotensin-aldosteron-system (RAAS), respectively, is the central mechanism to reduce cardio-vascular-renal end points as well as mortality.

Ein 69-jahriger Patient wurde mit einem Kreatininanstieg von 1,4 auf 4,9 mg/dl innerhalb von 4 Monaten, lividen, schmerzhaften Effloreszenzen an den Fusen, rezidivierender Epistaxis und Gleichgewichtsstorungen aufgenommen. In der Vorgeschichte waren drei kurzlich aufgetretene transitorische ischamische Attacken sowie ein metabolisches Syndrom bekannt. Im kranialen Magnetresonanztomogramm zeigten sich fleckformige vaskulitisahnliche zerebrale Signalanhebungen. Laborchemisch bestanden eine Eosinophilie sowie eine geringgradige Proteinurie vom tubularen Typ. Haut- und Nierenbiopsien erbrachten die Diagnose einer Cholesterinembolie als Ursache der Nierenfunktionsverschlechterung. Als mutmasliche Quelle der rezidivierenden Cholesterinkristallembolien lies sich eine massive Sklerose der Aorta sichern. Auch ohne vorausgehende angiographische Intervention muss bei rasch progredienter Niereninsuffizienz eines Atherosklerosepatienten insbesondere in hoherem Alter die Differentialdiagnose Cholesterinkristallembolie in Betracht gezogen werden.

The prevention of disease and the prevention of subsequent disease is one of the main themes in public health as well as in clinical medicine. Besides targeted interventions aiming at the total population (public health) individual steps like life style intervention and use of pharmacotherapy are important components. Taking acute myocardial infarction as an example it is illustrated, how risk factors can be targeted and which new drugs in development have been either just registered or are in late phase III of clinical testing shortly before registration and final approval. In this context it was shown that there are many exciting new options to reduce risk factors. On the other hand there are indications in which new drug development is likely not to contribute to an improvement of the situation (e. g. arterial hypertension) and in which further targeted intervention aiming at physicians (therapeutic pathways, guidelines, point of care research) and patients (life style intervention, compliance) has to be undertaken to improve the efficacy of currently available pharmacotherapy.

Risikofaktoren fur die Entwicklung kardiovaskularer Erkrankungen, insbesondere des akuten Myokardinfarkts, sind Nikotinabusus, Ubergewicht, wenig Bewegung, ungunstige Ernahrung, erhohter Blutdruck, erhohte Blutglucose bzw. Diabetes mellitus und eine Dyslipidamie. Wird ein Risiko fur kardiovaskulare Morbiditat in den nachsten 10 Jahren von 5% (nach dem SCORE-Score) oder fur nichttodliche kardiovaskulare Ereignisse von 20% (PROCAM-Score) uberschritten oder liegt eine Gefasatherosklerose oder ein Diabetes mellitus Typ 2 vor, ist zur Pravention kardiovaskularer Erkrankungen der Einsatz einer (Poly-)Pharmakotherapie angezeigt, eine Lebensstilanderung (Diat, korperliche Bewegung) allein reicht zu diesem Zeitpunkt in der Regel nicht mehr aus. Eine neue Therapieoption, die eine Reihe kardiovaskularer Risikofaktoren gleichzeitig gunstig beeinflusst, besteht in der Blockade des Endocannabinoidsystems. Fur die Substanz Rimonabant wurde in klinischen Studien nicht nur eine Reduktion des Korpergewichts bzw. des Taillenumfangs, sondern auch ein Anstieg des HDL-Cholesterins sowie eine Absenkung der Triglyzeride nachgewiesen. Daruber hinaus wurde auch eine Verminderung des HbA1c bzw. der Nuchternglucose beobachtet. Einschlieslich seiner nachgewiesenen Wirksamkeit in der Raucherentwohnung beeinflusst Rimonabant damit vier der acht vom American College of Cardiology und von der American Heart Association genannten relevanten Risikofaktoren zur Pravention des akuten Myokardinfarkts. Ein umfangreiches klinisches Studienprogramm zur Erforschung von Rimonabant im Rahmen des kardiovaskularen Risikomanagements wird gegenwartig durchgefuhrt. Die Substanz wird im Allgemeinen gut vertragen (haufigste Nebenwirkung: Ubelkeit). Die bislang veroffentlichten Studienergebnisse zeigen ein gutes Vertraglichkeitsprofil und sind vielversprechend im Hinblick auf den zukunftigen Stellenwert von Rimonabant im Rahmen des kardiovaskularen Risikomanagements.

Der Ubertritt von Albumin aus dem Gefaslumen in das umliegende Gewebe stellt immer eine ernsthafte Storung der Integritat des gesamten Gefassystems dar. Klinisch werden diese Veranderungen als „cotton-wool“-Herde in der Retina oder durch das Auftreten von Albumin im Urin erkennbar. Dabei steigt mit der Hohe der Albuminausscheidung das kardiovaskulare Risiko auch schon unterhalb der Schwellenwerte fur Mikroalbuminurie an. Ein Ubertritt von Albumin in das Gewebe stellt einen Hinweis auf eine Storung der Schrankenfunktion der Endothelzellen dar. In der Niere kommt es u.a. zu einer Schadigung von Podozyten, Mesangium- und Endothelzellen, einem Verlust der Ladungsselektivitat und einer veranderten Expression von Matrixproteinen. Diese Veranderungen sind aber nicht nur in den Nieren, sondern auch im Myokard nachweisbar. Die definierten Grenzen fur die Mikroalbuminurie (> 30 mg/24 h) und Proteinurie (> 300 mg/24 h) sind fur die kardiovaskulare Prognose jedoch nur eingeschrankt bedeutsam, da die Risikoerhohung bereits bei einer geringeren Albuminausscheidung beginnt. Die Pravalenz einer Mikroalbuminurie liegt in der Bevolkerung bei etwa 8%, in Hochrisikogruppen dagegen bei bis zu 50% und mehr. Sie ist mit einer Erhohung der kardiovaskularen Morbiditat und Mortalitat verbunden. Eine Reihe von therapeutischen Ansatzen (enge Blutzuckereinstellung, Blutdrucksenkung, Lipidsenker) fuhrt sowohl zu einer Verminderung der Albuminurie als auch zu einer Verbesserung der kardiovaskularen Prognose. Als zentraler Angriffspunkt der kardiovaskularen Protektiongilt die wirksame Hemmung des Renin-Angiotensin-Aldosteron-Systems (RAAS). RAAS-blockierende Substanzen sind nicht nur mit einer Verringerung von Endorganschaden (Herzinsuffizienz, diabetische Nephropathie, zerebrovaskulare Ereignisse) verbunden, sondern konnen auch zu einer Verminderung der Mortalitat fuhren. Die fruhzeitige Diagnose, eine grundliche kardiovaskulare Diagnostik und engmaschige Einstellung der kardiovaskularen Risikofaktoren unter konsequentem Einsatz von RAAS-blockierenden Substanzen erscheinen bei Patienten mit dem Nachweis einer Albuminurie angezeigt.

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

BACKGROUND Intradialytic hypotension (IDH) is one of the most severe complications during hemodialysis. Its appearance is caused in part by rapid fluid removal with concomitant failure in blood pressure regulation but also by other dialytic-dependent and independent factors. PATIENTS AND METHODS We investigated total (TBW), extracellular (ECW) and intracellular water (ICW) in chronic intermittent hemodialysis dialysis hypotension-prone (CRF-HP, n = 11) and nonhypotension-prone (CRF-NHP, n = 10) patients with end-stage renal disease before, every 30 minutes during, as well as after dialysis and within onset of intradialytic hypotension by multifrequent bioimpedance analysis (BIA). Additionally, intradialytic time course of BIA in patients with acute renal failure (ARF) and septic shock (n = 10) was observed. RESULTS IDH occurred in 72.1% of CRF-HP and in 80% of ARF patients. In CRF-HP and CRF-NHP, ECW significantly decreased by -12.44 +/- 4.22% in CRF-HP and -9.0 +/- 6.2% in CRF-NHP comparing pre- and post-dialysis values (each p < 0.01). Conversely, ICW increased by +11.5 +/- 11.3% in CRF-HP and +18.4 +/- 25.2% in CRF-NHP (each p < 0.05). In patients with ARF no significant changes could be detected. Calculated ECW/ICW and ECW/TBW ratio significantly decreased in CRF patients with a higher rate in CRF-HP patients (p < 0.05). Neither ECW/ICW nor ECW/TBW ratio correlated with mean arterial pressure. The onset of intradialytic hypotension (n = 35) did not differ intraindividually compared to normotensive periods (n = 411). Fluid removal in CRF patients seems to be mainly from the extracellular space. The reduced decreases in ECW/ICW and ECW/TBW ratios in CRF-HP compared to CRF-NHP may indicate an insufficient refilling from intra- to extracellular compartment in CRF-HP. CONCLUSION In conclusion, multifrequent BIA is not capable to predict hypotension in the individual patient during a particular dialysis session.

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.

Adipositas und arterielle Hypertonie sind epidemisch und treten oft in Kombination auf. Trotz der Haufigkeit und der Schwierigkeiten bei der Einstellung dieser Patienten gibt es keine aktuellen Daten zur Verschreibung von Antihypertensiva in der primararztlichen Versorgung bei dieser Patientenpopulation. Dazu wurden die Daten einer bundesweiten Beobachtungsstudie aus dem Jahre 2004 ausgewertet, die uber 70 000 Patienten mit arterieller Hypertonie untersuchte. Es wurde dokumentiert, welchen antihypertensiven Substanzklassen bei adiposen Patienten der Vorzug gegeben wird, welches die am haufigsten verwendeten Substanzen sind und wie diese dosiert werden. 1. Die antihypertensive Pharmakotherapie adiposer Patienten ist im Hinblick auf Substanzauswahl differenziert, aber nicht in der Dosierung. 2. Es werden haufiger als bei normalgewichtigen Vergleichspersonen Medikamentenkombinationen eingesetzt, um den Blutdruck dieser Patienten einzustellen. ACE-Hemmern und Diuretika wird hier der Vorzug gegeben. Diese Ergebnisse zeigen, dass die Verfugbarkeit einer grosen Zahl von antihypertensiven Medikamenten nicht ausreicht, um eine adaquate Einstellung des Blutdrucks zu gewahrleisten. Die fruhzeitige Kombination von antihypertensiven Medikamenten in reduzierter Dosierung (α-Blocker, β-Blocker, Diuretika und Calciumantagonisten) in Kombination mit hohen Dosen von Hemmern des Renin-Angiotensin-Systems (RAS) konnte zur Steigerung der Effektivitat bei gleichzeitiger Reduktion von Nebenwirkungen beitragen.

Eine 65-jahrige Patientin stellte sich mit einem seit 1 Tag bestehenden schmerzhaften Odem des rechten Arms vor. Seit 1988 ist bei der Patientin eine Polycythaemia vera (PV) bekannt. Die Gerinnungsparameter einschlieslich der D-Dimere lagen im Normbereich. Phlebographisch wurde eine Thrombose der proximalen rechten V. subclavia diagnostiziert. 1 Woche nach stationarer Aufnahme entwickelte die Patientin eine D-Dimernegative symptomatische Lungenembolie. Bei klinischem Verdacht auf ein thromboembolisches Ereignis reicht die negative Pradiktion der D-Dimer-Bestimmung als Ausschlusskriterium allein nicht aus. In diesem Fall sollte der Patient einer bildgebenden Diagnostik zugefuhrt werden. Aufgrund der erhohten Inzidenz thromboembolischer Ereignisse bei PV sollten die Patienten eine prophylaktische Thrombozytenaggregationshemmung, z. B. mit Acetylsalicylsaure 100 mg/d, erhalten.

Bone Morphogenetic Proteins (BMPs) gehoren zur Superfamilie des Transforming Growth Factor-β (TGF-β). Die Bedeutung dieser Proteine fur Regenerationsvorgange in Geweben und Organen wurde in den letzten Jahren zunehmend deutlicher. Vor allem Studien zur fotalen Entwicklung zeigen die wichtige Rolle dieser Proteine fur die Entstehung und Differenzierung von Organen, wobei fehlende oder mutierte BMPs zu Missbildungen oder sogar zum Abort fuhren konnen. Auch im erwachsenen Organismus wird zunehmend die regenerative Bedeutung dieser Proteine erkannt. So konnen die BMPs zur Heilung von Frakturen und zur Behandlung von Gelenkerkrankungen beitragen. Zur Behandlung von therapierefraktaren Frakturen wurde BMP-7 bereits fur den lokalen klinischen Einsatz zugelassen. Bei degenerativen Gelenkerkrankungen weisen experimentelle Daten auf eine verminderte BMP-Expression im Knorpelgewebe hin. Deshalb konnten BMPs einen neuen vielversprechenden Ansatz bei der Therapie dieser Erkrankungen darstellen. In dieser Ubersicht soll daher die Gruppe der Bone Morphogenetic Proteins vorgestellt und bisherige und mogliche zukunftige klinische Anwendungsgebiete diskutiert werden.

Clinical observations revealed an increased prevalence of iron deficiency anemia without chronic bleeding in patients treated with serial low-density lipoprotein (LDL) apheresis. Since several different proteins are adsorbed by LDL apheresis beside pro-atherogenic lipoproteins, we examined the modification of the full blood count, plasma iron, vitamin B12, folic acid, and hemolysis by LDL apheresis. Nineteen patients (55 (50-59) years, 4 female, 15 male) undergoing chronic LDL apheresis due to mixed dyslipidemia (N = 17), homozygous familiar hypercholesterolemia (N = 1) or isolated elevated lipoprotein(a) (N = 1) were included in this study. They were treated with direct adsorption of lipoproteins (DALI; N = 6), heparin-induced LDL-precipitation (HELP; N = 7) or double filtration plasmapheresis (DFPP; N = 6). The patients' full blood count, iron metabolism (plasma iron, ferritin, transferrin, transferrin saturation), vitamins involved in erythropoiesis (vitamin B12 and folic acid), and markers of hemolysis (haptoglobin and free hemoglobin) were analyzed directly before and after LDL apheresis. A single LDL apheresis session significantly decreased the levels (reduction in the median [25(th)-75(th) percentiles] of: ferritin 9.8 [1.3-18] %; P = 0.004), transferrin (12.1 [10.0-15.96] %; P = 0.0005), and vitamin B12 (17.8 [16.2-20.8] %; P = 0.0005). Thereby, transferrin and vitamin B12 were decreased in all (N = 19) and ferritin in 74% (N = 14) of the patients. Twelve out of 19 patients (63.2%) had mild anemia despite iron administration in 14 out of 19 patients (73.7%). LDL apheresis had no significant influence on full blood count, plasma iron, transferrin saturation, folic acid, or hemolysis. Similar changes were observed in all LDL apheresis methods used. LDL apheresis significantly decreases ferritin, transferrin, and vitamin B12, suggesting an influence of serial LDL apheresis on erythropoiesis.

In inflammatory bowel disease refractory to established therapies, treatment with biological agents such as monoclonal tumor necrosis factor-α antibodies is an established therapeutic option. However, application in renal allograft recipients is either not licensed or has not yet been systematically examined. Herein, we present 2 case reports of renal allograft recipients who had steroid-refractory ulcerative colitis who demonstrated improvement of symptoms after treatment with infliximab, without signs of effect on transplant function. In both patients, stool frequency decreased significantly. Colonoscopy controls and histologic examination after initiation of treatment revealed a state of remission. Renal function parameters and drug concentrations remained constant.

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.

Plasma exchange (PE) is used for blood purification to modulate proteins involved in pathological processes. As the number of patients receiving PE treatment and the heterogeneity of the underlying diseases is steadily increasing, we evaluated the most frequent complications and analyzed causes leading to adverse reactions. 883 PE procedures in 113 patients between the years 2000 to 2006 were retrospectively analyzed with respect to complications. Additionally, underlying diseases and settings of PE procedure were analyzed to identify high-risk patients and respective PE settings. A total of 226 adverse reactions were recorded (25.6% of all PE procedures). Most complications were mild (n = 121, 13.7%) or moderate (n = 98, 11.0%). In seven cases (n = 7, 0.7%), severe, life-threatening adverse events were induced by PE either due to severe allergic reactions (n = 4, 0.5%) or to sepsis (n = 3, 0.3%). Patients with neurologic diseases had a significantly higher risk to develop complications compared to those with internal diseases (P = 0.013). This was due to a higher rate of PE associated adverse events (in particular hypotension) and complications associated with vascular access. Among patients from internal medicine those with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) had the highest risk to develop complications. Patients with neurological diseases compared to those with medical conditions and patients with HUS/TTP compared to those with other diseases had a higher risk to develop complications. However, severe adverse events are rare. Thus, PE seems to be a safe and recommendable procedure.

Risk factors for the development of cardiovascular disease, in particular myocardial infarction, are smoking, high body weight, sedentary lifestyle, unfavorable diet, high blood pressure, elevated fasting glucose or diabetes, and dyslipidemia (Tables 1 and 2). If the risk for cardiovascular mortality of 5% (using the SCORE Score) or for nonfatal cardiovascular events of 20% (PROCAM Score) within the next 10 years is exceeded or overt atherosclerosis or type 2 diabetes mellitus is present, the use of (poly)pharmacotherapy is indicated and lifestyle intervention (diet, physical activity) alone is not sufficient at that point (Figure 1). A new therapeutic option, able to modify a number of cardiovascular risk factors at a time, is the blockade of the so-called endocannabinoid system (Figure 2). For rimonabant not only a reduction of body weight and waist circumference was shown in clinical trials, its use was also accompanied by an increase of HDL cholesterol, a decrease in triglycerides, and a reduction in HbA1c and fasting blood glucose (Table 4). Together with preliminary data on the efficacy in smoking cessation, rimonabant has a therapeutic impact on four out of eight relevant risk factors in order to prevent myocardial infarction as promoted by the American College of Cardiology/American Heart Association. Currently, a large clinical study program is ongoing to further investigate the role of rimonabant in managing cardiovascular risk (Table 3). Published clinical trial results have revealed, that rimonabant is generally well tolerated (most frequent side effect: nausea) and the data are promising with regard to the potential future role of rimonabant in managing cardiovascular risk.

The transition of albumin from the vascular lumen into the surrounding tissue always indicates a serious disturbance of the vascular wall. Clinically, this process can be recognized as "cotton-wool" spots of the retina or by testing the urine for the presence of albumin. The appearance of albumin in the urine is pathologic and should be evaluated within the context of the accompanying cardiovascular risk.Albumin transition is indicative of a disturbance of the barrier function of endothelial cells. In the kidney, damage to podocytes, mesangial and endothelial cells, a loss of charge selectivity, and an altered expression of matrix proteins can be observed. However, vascular alterations are not confined to the kidney but can also be observed in the myocardium. Even though thresholds for microalbuminuria (30 mg/24 h) and proteinuria (300 mg/24 h) have been arbitrarily defined, an increase in risk starts at much lower levels of albumin excretion.The prevalence of microalbuminuria in the general population is about 8%. However, prevalence rates of50% have been observed in high-risk groups, which are accompanied by an increased risk for cardiovascular morbidity and mortality.A number of therapeutic options (tight blood sugar control, blood pressure reduction, lipid lowering) lead to a reduction of albuminuria and an improvement in cardiovascular prognosis. This has particularly been described for renin-angiotensin-aldosterone system-(RAAS-)blocking agents. Their use is not only associated with a reduced risk of end-organ damage (heart failure, diabetic nephropathy, cerebrovascular events) but has been described to decrease mortality as well.A timely diagnosis, a consecutive cardiovascular diagnostic work-up and the subsequent use of RAAS-blocking agents is indicated in patients in whom albuminuria has been diagnosed.

A 3 8-year-old pregnant woman (19th week of pregnancy) complained of fatigue, cold inducible paresthesias, generalized edema and mild arterial hypertension. Her past medical history was notable for frequent episodes of polyarthralgia and positivity for rheumatoid factor. On admission, acanthocyturia and unselective glomerular-tubular proteinuria with 19 g/d were detected with a slight decrease in creatinine clearance. Rheumatoid factor was robustly elevated and a cryocrit of 1.5 vol%, caused by a so far unknown replicative hepatitis C, was detected. Renal biopsy yielded membranoproliferative glomerulonephritis. During pregnancy, high-dose corticosteroid therapy was administered. Edema disappeared and blood pressure normalized under albumin substitution and low-dose furosemide application. However, Cesarian section became necessary due to placental insufficiency at 27 weeks of gestation. Thereafter, neither virus load, cryocrit nor proteinuria decreased significantly under a combined therapy with pegylated interferon-a and ribavirin. Thus, cryoprecipitate apheresis was initiated resulting in robust decreases of clinical complaints, viral load, cryocrit and proteinuria. Cryoglobulinemia with renal involvement caused by hepatitis C is difficult to treat due to limitations of immunosuppressive and anti-viral therapy. In our patient, cryoprecipitate apheresis was a safe and effective therapeutic addition to standard therapy.

A 65-year-old patient with polycythemia vera (PV) was admitted with a painful edema of the right arm lasting for 24 h. The D-dimer assay was negative. By phlebography the patient was diagnosed with a fresh thrombosis of the right subclavian vein. 1 week later she developed a D-dimer-negative symptomatic pulmonary embolism.If clinical signs of a thromboembolic event are present, the negative predictive value of the D-dimer assay is not sufficient to abandon further definitive diagnosis. Since thromboembolic events are frequent in PV patients, a prophylactic treatment with low-dose acetylsalicylic acid is recommended.

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.