The patient is a 49-year-old woman who has required dialysis for 3 years. Her renal disease was related to 30 years of anorexia nervosa.1.Luthra M. Davids M.R. Shafie M.A. et al.Anorexia nervosa and chronic renal insufficiency: a prescription for disaster.Q J Med. 2004; 97: 167-178Crossref Scopus (9) Google Scholar Her urinary output was <100 ml/day. She was referred because of metabolic acidosis before every dialysis treatment. Her HCO3− was ≤10 mmol/l and her arterial pH was <7.2. Occasionally lower values were observed. She denied any complaints and denied ingesting anything other then her prescribed medications; namely, a proton pump inhibitor, candesartan, CaCO3, cinacalcet, erythropoietin, iron, and a vitamin preparation. NaHCO3 tablets, 100 mmol/day, did not improve the acidosis. She was dialyzed with a bicarbonate bath and invariably left the unit with a normal serum HCO3−. The patient was referred to us for acidosis workup. Before her next scheduled dialysis, her pH was 7.19, PaCO2 28 mm Hg, and HCO3− 10.4 mmol/l. The Na+ level was 132, Cl− 95, and K+ 4.2 mmol/l. The osmolality was 287 mOsm/kg H2O, creatinine 459 μmol/l, and lactate 0.54 mmol/l. The other laboratory values were within the normal range or commensurate with the dialysis state. As she had an anion gap of 27 mmol/l, she was examined for the presence of ethanol, ethylene glycol, and methanol, which were all found to be absent. Ketones were negative. Her salicylate level was 9.9 μg/ml. We reasoned that toluene intoxication was unlikely. Table 1 shows acid–base relevant blood gas and electrolyte results before dialysis on admission, after dialysis, on the next day, and before the next dialysis in the hospital.Table 1Excerpts from arterial blood gas and electrolytes at four different time pointsBefore dialysisAfter24 h laterBefore next dialysispH7.197.477.337.09PaCO2 (mm Hg)28354142HCO3− (mmol/l)10252112Na+ (mmol/l)132139137139Cl− (mmol/l)9510198102AG (mmol/l)27131625Abbreviation: AG, anion gap. Open table in a new tab Abbreviation: AG, anion gap. What caused her acidosis? We discussed the situation with the patient further. She admitted to ingesting three packages of Mentos chewable dragees, at least one tablespoon of vitamin C powder, and 10 bags of Ahoj Brause (seltzer that makes a fizzy drink) per day. The dragees were harmless and contained no notable acids. The vitamin C level in her admission serum was 500 mg/l (normal 4.6–14.9 mg/l) and might have contributed to oxalosis and renal failure, but this explained only about 1/3 of the increased anion gap.2.Nasr S.H. Kashtanova Y. Levchuk V. et al.Secondary oxalosis due to excess vitamin C intake.Kidney Int. 2006; 70: 1672Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Ahoj Brause is a generous source of tartaric acid and contains 1.044 g per bag. Tartaric acid provides 150 g/mol, so we calculated her daily intake at about 70 mM per day. We dissolved an Ahoj Brause bag in a glass of water; the mixture had a pH <3. After dialysis, the patient's acid–base status normalized. We performed nuclear magnetic resonance spectroscopy in plasma before and after dialysis (Figure 1). We attributed the saccharose peak to the saccharose-containing Ahoj Brause. The glucose (Glc signals) peaks are dependent on proton positions. Thereafter came the vitamin C peak and a peak corresponding to tartrate. After dialysis, the saccharose peak, the vitamin C peak, and the tartrate peak were gone. The patient's daily tartrate load could account for the rest of the anion gap and the bulk of the metabolic acidosis. Wine drinkers recognize tartaric acid as the source of ‘wine diamonds,’ the small potassium bitartrate crystals that sometimes form spontaneously on the cork. The German word is indeed, ‘Weinsäure’. The tartrate diamonds are harmless, despite sometimes being mistaken for broken glass. Yeast and bacteria metabolize tartrate with various facilities depending on the concentration of the D or L isoform. Glyceric acid is a breakdown product, but oxalo-acetic acid and glyoxylic acid are intermediates. The rate of tartrate metabolism in humans is unclear. However, renal failure interferes with tartrate elimination. Recently, the effects of dietary potassium tartrate were investigated in rats.3.Sabboh H. Coxam V. Horcajada M.N. et al.Effects of plant food potassium salts (citrate, galacturonate or tartrate) on acid-base status and digestive fermentations in rats.Br J Nutr. 2007; 98: 72-77Crossref PubMed Scopus (10) Google Scholar The animals excreted about half the ingested tartrate unmetabolized in the urine. Our patient could of course excrete no tartrate, which probably contributed to her clinical picture. There are no reports of tartaric acid or ascorbic acid-induced metabolic acidosis in the literature. Thus, we venture to claim the first report of Ahoj-Brause tartrate-associated metabolic acidosis, although we cannot dismiss a small contribution by vitamin C. SE, RK, and FCL managed the patient, HH identified the problem and referred the patient, ST and DL were responsible for the magnetic resonance spectroscopy, SE and FCL prepared the report.

Proven strategies to reduce cardiovascular events and cardiac mortality in hemodialysis patients are given on the basis of pathophysiology. This is an overview of our clinical know-how acquired during the last 30 years. We try to answer the following questions: (1) how to reduce cardiovascular events and cardiac mortality in hemodialysis patients; (2) how to achieve regression of left ventricular hypertrophy, the most important predictor of sudden cardiac death; (3) how to manage iron status during full correction of renal anemia to prevent iron deficiency-induced reactive thrombocytosis, which is recognized to cause fatal stroke and cardiovascular thrombosis; (4) how to maintain responsiveness to erythropoiesis-stimulating agents during correction of renal anemia, thereby avoiding unnecessarily high doses and so reaching ultimate cost-effectiveness. Conclusion: Normalization of renal anemia is not responsible for increased risk of cardiovascular events/cardiac mortality. The inability to adequately address iron status in hemoglobin normalization studies and the underprescription of effective cardiac/antihypertensive medication might explain the adverse outcome. Effective cardiac/antihypertensive medication, intensive iron therapy during normalization of hemoglobin, optimized correction of metabolic acidosis and supplementation of vitamins which are involved in the energy metabolism should be considered to significantly improve the outcome of hemodialysis patients.

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) are apparently exposed to enhanced oxidative stress and to inflammation. It was the aim of this study to characterize the state of systemic oxidative stress of ESRD patients before and following HD using highly specific biomarkers, F-2-isoprostanes and 4-hydroxynonenal (HNE). Furthermore the question should be answered, if there are associations between inflammation and systemic oxidative stress and/or between systemic oxidative stress and renal anemia, which is more or less typical for HD patients.Patients and methods: Concentrations of F-2-isoprostanes, HNE, C-reactive protein (CRP) as marker of inflammation, and hemoglobin were measured in serum samples of patients with ESRD before and after HD and of healthy control persons for comparison. Total (esterified plus free) F-2-isoprostanes were quantified by highly sensitive gas chromatography/ mass spectrometry technique, HNE by thin layer chromatography and HPLC/UV detection, CRP by immunoturbidimetry and hemoglobin by clinico-chemical routine assay.Results: 1. HD patients showed significantly higher serum concentrations of F-2-isoprostanes and HNE than healthy human control subjects. 2. Total (esterified plus free) F-2-isoprostane levels before HD were not significantly different from those after HD, whereas HNE levels were significantly decreased in patients after HD. 3. F-2-isoprostane concentrations in HD patients correlated with the levels of CRP, whereas HNE concentrations inversely correlated with the content of hemoglobin.Conclusion: Both, F-2-isoprostanes and HNE serum concentrations are useful oxidative stress parameters in ESRD patients undergoing HD. Whereas HNE strongly correlates with the severity of renal anemia, leading to left heart insufficiency, F-2-isoprostanes (sum of free plus esterified) highly correlate with the degree of inflammation.

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 (beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) with full anemia correction by intravenous epoetin-beta. The dose of epoetin-beta 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/m(2); 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.

BACKGROUND/AIMS:Oxidative stress occurs in chronic renal failure patients undergoing hemodialysis (HD). The objective of our study was to measure oxidation products of cholesterols, so-called oxysterols, in the serum of HD patients in comparison to healthy control persons. METHODS:In 42 HD patients, plasma oxysterols were measured before and after HD. The values were compared with those in 40 healthy controls. The following cholesterol derivatives were analyzed: dienes, 7beta-OH, beta-epoxy, alpha-epoxy, 20alpha-OH, alpha-triol, and 7-keto cholesterol. RESULTS:In HD patients, serum levels of oxysterols are increased in comparison to controls. The highest values were measured for beta-epoxy cholesterol and for 20alpha-OH cholesterol. During HD oxysterol concentrations increased, obviously by water removal and concentration of nondialyzable compounds. CONCLUSION:Due to oxidative stress which is known as a typical sign of chronic renal failure the plasma concentrations of oxysterols are also significantly increased in comparison to healthy controls. This underlines the data on accelerated lipid peroxidation in end-stage renal disease (ESRD) patients. Accumulated oxysterols which are accused of exerting atherosclerosis-stimulating effects, which can contribute to the increased cardiovascular risk of ESRD patients, could either induce atherosclerosis via signaling or chronic effects. Direct chemical reactions stimulating plaque formation can be excluded because of the low levels of oxysterols. The share of oxysterols within the total cholesterol ranges from 4 to 15 per thousand.

Background: According to new guidelines, diabetes mellitus per se can be considered as stage I chronic heart failure (CHF). Available evidence suggests that patients suffering from both diabetes mellitus and renal insufficiency have disproportionately high rates of left-ventricular hypertrophy (LVH). Methods: Optimized heart failure therapy, including β-blockers, ACE-inhibitors and AT II-type-1-receptor-blockers, was prescribed in combination with complete anemia correction using epoetin beta (target hemoglobin: 13.5 g/dl for women; 14.5 g/dl for men) to 230 patients (55% male) with ambulatory hemodialysis, including 60 patients (52% male) with diabetes. Echocardiographic follow-up examinations were performed over a mean period of 4.4 ± 1.2 years. Results: Mean hemoglobin levels at the study end significantly increased to target levels in the entire study population and in patients with diabetes (both p < 0.001). Compared with baseline, significant improvements were seen in hemodialysis patients – both without and with diabetes – in left-ventricular mass index (–28.8 g/m2 [p < 0.001] and 29.0 g/m2 [p < 0.005], respectively), left-ventricular ejection fraction (+7.0% [p < 0.001] and +8.3% [p < 0.01], respectively) and in NYHA class (–0.84 [p < 0.01] and –1.12 [p < 0.01], respectively). Similar to the results in the overall population, a highly significant reduction in LVH (p < 0.005) and significant improvements in LVEF (p < 0.01) and NYHA class (p < 0.01) were seen in the high-risk subgroup of diabetic patients. Conclusions: Patients undergoing hemodialysis, with or without concomitant diabetes, benefit considerably from optimized, multifactorial heart failure therapy combined with complete anemia correction.

Patients with end-stage renal disease (ESRD) represent a growing number of patients in the cardiac catheterization laboratories worldwide. This is a consequence of the growing absolute number of ESRD patients in developed countries, better noninvasive diagnostic tools, better catheterization facilities and last-but-not-least better education of referring physicians about the incidence and prognosis of coronary artery disease (CAD) for patients with ESRD. There is growing evidence of the positive impact of coronary revascularization on long-term outcome of these patients. ESRD patients have a high comorbidity and are therefore better candidates for the less invasive approach using percutaneous coronary intervention (PCI) rather than coronary artery bypass surgery (CABG). From the view of the interventional cardiologist, ESRD patients represent one of the most challenging patient cohort concerning technical challenges and potential risk of complication for the patient. Percutaneous coronary intervention (PCI) including debulking techniques and stent implantation is the current standard therapy for patients with symptomatic single-vessel disease (SVD) and the preferred therapy for most patients with focal, polyfocal or even diffuse multi-vessel disease (MVD). Coronary bypass surgery is reserved for a dePublished online: March 7, 2006 Priv.-Doz. Dr. med. Wolfgang Bocksch, Department of Internal Medicine-Cardiology Cardiac Catheterization Laboratories, Charité-Campus Virchow-Klinikum Universitätsmedizin Berlin, Humboldt Universität zu Berlin and Freie Universität Berlin Augustenburger Platz 1, DE–13353 Berlin (Germany) Tel. +49 30 450 553 283, Fax +49 30 450 553 961, E-Mail wolfgang.bocksch@charite.de © 2005 S. Karger AG, Basel 1420–4096/05/0286–0275$22.00/0 Accessible online at:

Chronic renal failure patients on long-term hemolysis are found to be under increased oxidative stress, caused by antioxidant deficiency, neutrophil activation during hemodialysis (HD), platelet activation and/or chronic inflammation. Increased levels of oxidants (e.g. malondialdehyde, 4-hydroxynonenal, hydrocarbons, lipohydroperoxides, oxycholesterols, carbonyls) in HD patients are thought to play an important role in the development of endothelial dysfunction, atherogenesis and cardiovascular disease, which is a frequent condition in end-stage renal disease. F2-isoprostanes have been established as chemically stable, highly specific and reliable biomarkers of in vivo oxidative stress which can very sensitively measured by gas chromatography-mass spectrometry (Morrow et al. [17]). An up to 6-fold increase of plasma F2-isoprostanes in HD patients is accompanied by an enhanced formation of indicators of inflammation (e.g. C-reactive protein) and decreases of endogenous antioxidants (e.g. ascorbate, alpha-tocopherol). In their esterified form F2-isoprostanes may be a useful criteria to evaluate the effectiveness of clinical interventions to diminish oxidant stress and associated inflammation. Furthermore, F2-isoprostanes possess potent biological activities (e.g. 8-iso-PGF2alpha is known as a renal vasoconstrictor) suggesting that they may also act as mediators of the cellular effects of oxidative stress and inflammation.

BACKGROUND/AIMS:Oxidative stress often occurs in chronic hemodialysis (HD) patients. The objective of our study was to investigate the interrelationship between oxidative stress and the degree of renal anemia.METHODS:In 107 consecutive HD patients, serum concentrations of two major aldehydic lipid peroxidation (LPO) products, 4-hydroxynonenal (HNE) and malondialdehyde (MDA), and of protein carbonyls were analyzed as parameters of oxidative stress and related to the degree of renal anemia. Additionally, in 76 patients treated with epoetin long-term changes in the serum levels of aldehydic LPO products were observed.RESULTS:In HD patients, serum levels of HNE, MDA, and protein carbonyls are increased in comparison to controls. The lower the hemoglobin, i.e. the stronger the degree of renal anemia, the higher the serum concentrations of HNE, MDA, and protein carbonyls. The HNE and MDA levels decreased during HD. Long-term studies on the correction of renal anemia by epoetin demonstrated a mitigation of oxidative stress during this therapy. During periods of 1 and 2 years, it was observed that the serum levels of HNE and MDA could be reduced.CONCLUSION:Chronic renal failure is connected with oxidative stress which correlates with the degree of renal anemia, and the serum levels of aldehydic LPO products could be reduced during correction of renal anemia by epoetin.

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.