Kai Uwe Eckardt

..Rigorous strategies of blood conservation may help to avoid transfusions. Red blood cell substitutes and recombinant erythropoietin are promising treatment options that are currently under investigation...

..Less then 10% of patients receive EPO prior to the onset of dialysis, the mean hemoglobin level at the start of dialysis is not higher than 9 g/dl and a significant proportion of patients permanently remain below 11 g/dl...

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..While the majority of HIF-dependent genes confer protection against hypoxia, hypoxia-inducible gene expression has been suggested to contribute also to increased interstitial matrix deposition...

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..Cardiomyocytes and cardiac stromal cells exhibit a marked potential for a prolonged transcriptional response to ischemia mediated by HIF. The induction of HIF-1alpha and -2alpha appears to be complementary rather than solely redundant...

..This structural change, although located at distance to the HIF-binding region, was found to inhibit binding of HIF-1alpha to VHL, thus leading to accumulation of HIF, which drives EPO production...

..Hypoxia-inducible transcription factors (HIF) are recognized as master regulators of hypoxic adaptation, but little is known about their role in renal disease...

..In conclusion, we found a remarkably restricted target gene specificity of the HIFalpha subunits, which can be overcome in cells with perturbations in the pVHL/HIF system and under forced expression...

..Therefore, in calciphylaxis BMP-4 can play the role of a cytokine, a growth factor or a media-calcification promoter...

..Elevation of collagen fragments has been demonstrated in the serum and urine of patients with renal disease, but the dynamics of renal matrix deposition remain difficult to determine...

..Furthermore, such a cycle may exist in psoriasis in dermal capillaries and contribute to disease progression...

..Further, it is not known whether ARF is an independent risk factor for mortality in septic patients or merely an indicator of disease severity...

..ACS evolving to acute respiratory distress syndrome (ARDS) is a rare but severe complication. In ACS iNO should be considered a beneficial therapeutic option...

..In spite of this syndrome's grim prognosis, the patient recovered following intensive anticoagulation and adjunct treatment with steroids and immunoglobulins...

..Patients and..

..Since in the IPK distal tubular damage inversely correlates with HIF activation (Rosenberger, KI, 2005), we explored the potential of PHD-I to improve morpho-functional outcome in this model...

..In conclusion, the data provide proof of principle that preconditional activation of the HIF system protects against ischemic injury. Inhibiting the activity of HIF hydroxylases therefore seems to have considerable clinical perspectives...

..As with other anemias, the consequences of renal anemia are a moderate decrease in tissue oxygen tensions and counterregulatory mechanisms that maintain total oxygen consumption, including a persistent increase in cardiac output...

..Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established...

..Moreover, it will be discussed whether patients with sepsis and septic shock benefit from early RRT initiation, the use of increased RRT doses, and increased removal of inflammatory mediators by RRT...

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..Studies utilizing HIF-stimulating agents proved efficacy in various kidney disease models, suggesting that HIF activation is an ideal target of future therapeutic approaches...

..Indirect evidence suggests that hypoxia contributes to the pathophysiology of rhabdomyolysis-induced acute kidney injury (AKI). However, the cellular location and kinetics of hypoxia, as well as potential hypoxia adaptation are unclear...

..Therefore, development of pharmacologic agents to induce renal HIF might provide a new approach to ameliorate cisplatin-induced nephrotoxicity...

..To assess the therapeutic equivalence of epoetin zeta and epoetin alpha for correction of haemoglobin (Hb) concentration in patients with anaemia and chronic kidney disease (CKD) stage 5 maintained on haemodialysis...

..However, overall, the importance of hyperparathyroidism appears to be minor compared with other factors such as iron deficiency or inflammation...

..CONCLUSION: Our findings illustrate a marked potential of renal tissue to respond to regional ischemia and initiate adaptive reactions, including angiogenesis...

..These data indicate that HIF-2 plays an important role in the transcriptional response to hypoxia in vivo, which is not confined to the vasculature and is complementary to rather than redundant with HIF-1...

..INTERPRETATION: Immunosuppressive treatment accelerates recovery from erythropoietin-induced pure red cell aplasia...

..The expression of HIF-2alpha in peritubular fibroblasts suggests a role in erythropoietin regulation...

..In conclusion, these data strongly suggest that leachates were the critical contributory factor in the increased incidence of antibody-mediated PRCA attributed to EPREX/ERYPO...

..PCT was elevated a median of 2 days earlier than the clinical diagnosis of VAP. Elevations in PCT can, therefore, indicate bacterial complications in cardiac arrest patients with a non-infectious acute phase response...

..Among emerging CVD risk factors, oxidative stress is currently being given emphasis...

..Interventional strategies to inhibit survivin's function in malignancy need to be carefully (re)evaluated for renal side effects, as well as for other possible organ dysfunctions...

..Oxygen-independent activation of HIF is therefore a promising therapeutic strategy for the prevention of organ injury and failure...

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..The present publication reviews the arguments based on which this decision was taken...

..These results demonstrate that in mice the skin is a critical mediator of systemic responses to environmental oxygen...

..The Cardiovascular risk Reduction by Early Anaemia Treatment with Epoetin beta (CREATE) study is investigating whether this approach is associated with a measurable reduction in cardiovascular risk...

..Anti-EPO antibodies crossreactive with epoetin-beta and darbepoetin-alpha were demonstrated in patient serum. PRCA gradually improved after treatment with prednisolone...

..Thus, HIF-2alpha effects are modulated by a number of intrinsic and extrinsic factors which may be most relevant in tumour cells...

..Induction of BNP may therefore contribute to the potential benefits of pharmacological HIF inducers in the treatment of ischaemic heart disease and heart failure...

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..Kidney disease treatment by dialysis and transplantation should be noted. Simple, uniform classifications of CKD by cause and by risks for kidney disease progression and CVD should be developed...

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..Its stated mission is "Improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration and integration of initiatives to develop and implement clinical practice guidelines."..

..Hemodynamic improvement seemed to be related to endogenous cortisol levels, whereas immune effects appeared to be independent of adrenal reserve...

..Inducibility of PHD2 and 3 by hypoxia and ischemia in vivo has important implications both for the pathophysiology of conditions where oxygen supply is deranged and for attempts to manipulate the HIF system therapeutically...

..We review these new therapeutic strategies, and discuss at what stage some of the newer products are in relation to their clinical development programme...

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..Diabetic nephropathy has become the major cause of end-stage renal disease (ESRD) in the western world and is forecast to become the most frequent cause of ESRD in the African continent and in developing countries in other areas...

..On the other hand, continuous activation of the HIF system occurs in kidney cancer and potentially promotes tumor growth. HIF therefore also is explored as a target for anticancer therapy...

..Further to the reported expression of EPO receptors in tumour tissues, the finding of widespread expression of EPO in RCC supports the recent notion of an involvement of this system in paracrine or autocrine effects of tumour cells...