Radical generation in HD patients might be caused in part by renal anemia itself. Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration.

Background: In chronic hemodialysis (HD) patients, the presence and degree of left ventricular hypertrophy (LVH) correlates with mortality. Previous studies have shown that interventions, such as anemia correction or treatment of hypertension and/or chronic heart failure (CHF), can result in moderate regression of LVH. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH in HD patients. Methods and Results: In a series of 202 consecutive HD patients, we combined optimized CHF therapy, including β-blockers (BB), ACE inhibitors and angiotensin receptor blockers (ARBs), to target doses with full anemia correction by epoetin β (hemoglobin (Hb) target males 14.5 g/dl, females 13.5 g/dl). Serial echocardiograms were recorded every 3–6 months. Mean follow-up was 3.4 ± 1.2 years. Mean Hb at baseline was 11.4 ± 1.4 vs. 14.6 ± 1.6 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI, 159 ± 65 vs. 132 ± 46 g/m² (p < 0.001)), an improvement in left ventricular ejection fraction (LVEF, 60 ± 15 vs. 66 ± 12% (p < 0.01)) and in NYHA class (2.8 ± 0.76 vs. 1.96 ± 0.76 (p < 0.01)) from baseline to follow-up in the overall study population. In a subgroup of 70 patients, LVMI returned to normal (169 ± 33 vs. 114 ± 14 g/m² (p < 0.001)) after 1.4 ± 1 years. Conclusions: Our study shows that optimized CHF therapy, in combination with anemia correction to normal Hb targets, results in a significant reduction of LVH, an increase in LVEF and an improvement in NYHA class. Moreover, in contrast to previous studies, our data also demonstrate that complete regression and prevention of LVH in HD patients is possible.

In hemodialysis patients, free amino acids and α-ketoacids in plasma were determined by fluorescence HPLC to assess the effect of α-ketoglutarate administration in combination with the phosphate binder calcium carbonate on the amino acid metabolism. During 1 year of therapy in parallel to inorganic phosphate, urea in plasma decreased significantly, histidine, arginine and proline as well as branched chain α-ketoacids, in particular α-ketoisocaproate, a regulator of protein metabolism, increased. Thus, administration of α-ketoglutarate with calcium carbonate effectively improves amino acid metabolism in hemodialysis patients as it decreases hyperphosphatemia.

Lipopolysaccharides (LPS, endotoxin) of Gram-negative bacteria are among the main causes of sepsis and septic shock. In the present study, the influence of temperature on the biological activity of LPS was investigated. Lowering the temperature from 37°C to 34.5°C or to 30°C significantly enhances in vitro tumor necrosis factor-A (TNF-A), interleukin (IL)-1β and IL-6 release induced by different LPS chemotypes and heat-inactivated Escherichia coli. This cytokine-increasing effect of lowering the temperature is highly mediated by serum proteins, particularly by LPS-binding protein (LBP) and low-density lipoproteins (LDL). In contrast, cytokine production induced by the superantigen toxic shock syndrome toxin-1 (TSST-1) from Gram-positive Staphyloccoccus aureus decreases by around 70% at 30°C as compared with 37°C, corresponding to the expected effect of change in temperature and regardless of the presence of serum proteins. In order to explain the unexpected biological hypothermia effect with regard to LPS, the fluidity state of the lipid A portion of LPS as one important physico-chemical property possibly involved was investigated. The fluidity, determined by fluorescence polarization measurements, was found to decrease with decreasing temperature. These data suggest that a low fluid LPS chemotype is biologically more active than a more fluid one (and vice versa). Statistical analysis of the results shows a strong correlation between cytokine secretion and fluidity state of a given LPS chemotype (0.71 Ͻ r Ͻ 0.89, all P Ͻ 0.01). As a clinical consequence, these data may be one possible explanation for the higher mortality rate of hypothermic Gram-negative sepsis.

Background: In hemodialysis patients, left ventricular hypertrophy (LVH) correlates with mortality. The reason for LVH in uremics is multifactorial. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH. Methods: In 230 ambulatory patients, including patients with coronary artery disease, diabetes, diastolic and systolic dysfunction, we continued optimized cardiac therapy (β-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) with full anemia correction by intravenous epoetin-β. The dose of epoetin-β for maintaining target hemoglobin (Hb) was 68 ± 23 IU/kg/week. Serial echocardiograms were recorded every 3–6 months. The mean observation period was 4.8 ± 1.2 years. Results: Mean Hb at baseline was 11.2 ± 2.0 versus 14.1 ± 1.4 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI: 159 ± 50.4 vs. 130.2 ± 42.7 g/m²; p < 0.001). In a subgroup of 2/3 of the patients, LVMI returned to normal (169 ± 33 vs. 114 ± 14 g/m²; p < 0.001). Conclusion: Baseline LVMI (p < 0.001), Hb increase (p < 0.03), and triple cardiac therapy (p < 0.03) were significant and independent prognostic factors for a reduction in LVMI. The annual cardiovascular mortality was 5%. Even anemia correction from 12 to 14 g/dl results in further (p < 0.001) regression of LVMI.