Removal of contrast media by different extracorporeal treatments.

BACKGROUND: Although the capability of extracorporeal treatments after administration of contrast media to prevent radiocontrast-induced nephropathy is controversial, haemodialysis is performed in many institutions after radiographic procedures. There are conflicting reports on the efficacy of different dialysers and treatment modalities to remove contrast media. METHODS: We compared the contrast medium-removing ability of different extracorporeal treatments in a randomized trial. Thirty-nine patients on chronic renal-replacement therapy or with chronic renal failure were randomized to receive low-flux haemodialysis (Low-HD, n=10), high-flux haemodialysis (High-HD, n=10), online haemodiafiltration (HDF, 10 litre substitution, n=10) and online haemofiltration (HF, 18 litre substitution, n=9) after administration of contrast medium during routine radiological procedures. Plasma concentrations of contrast medium (iopromide or iomeprol) were measured by energy-dispersive X-ray fluorescence analysis. RESULTS: The extraction ratio for contrast media was 0.64+/-0.1 for Low HD (P<0.05 vs. High-HD and vs. HDF), 0.74+/-0.1 for High-HD (P<0.05 vs. HF), 0.81+/-0.1 for HDF (P<0.05 vs HF), and 0.62+/-0.1 for HF. Mean extracorporeal plasma clearances were 82+/-2 for Low-HD (P<0.05 vs. High-HD and vs HDF), 100+/-2 for High-HD, 115+/-4 for HDF (P<0.05 vs. HF), and 86+/-5 ml/min for HF. CONCLUSIONS: We conclude that HDF and High-HD remove contrast media more effectively than Low-HD and HF during the time of each treatment session. However, whether this is also true for the overall elimination of contrast media by these different procedures needs to be addressed in future studies, by a precise assessment of the drug time course after the session.

Oxidation parameters in complete correction of renal anemia.

UNLABELLED: Chronic hemodialysis (HD) patients are more exposed to oxidative stress, with its adverse impact on many cell functions and not least on patient survival. There is evidence that partial correction of renal anemia by erythropoietin (rhEPO) therapy reduces oxidative stress. The aim of this study was to clarify whether complete correction of renal anemia with rhEPO reduces free radical generation in HD patients and increases antioxidant supply. The following parameters: malondialdehyde (MDA), reduced glutathione (GSH) and glutathione disulfide (GSSG) were investigated in patients with a hematocrit (Hct) normalized on rhEPO therapy (Hct > or = 0.4), and compared with those in anemic patients (Hct 0.3 - 0.39 and Hct < 0.3). The groups were similar in age, sex or body weight. Patients with normal Hct were significantly longer in the chronic HD program (74.0 +/- 70.3 vs. 23.0 +/- 30.9 and 30.6 +/- 34.8 months; p < 0.05) and received significantly lower doses of iron (35.7 +/- 19.5 vs. 55.4 +/- 26.0 and 80.0 +/- 47.1 mg/week; p < 0.05) and rhEPO (68.9 +/- 63.6 vs. 106.5 +/- 63.9 and 152.8 +/- 86.0 IU/kg/week; p < 0.05). MDA levels were significantly lower in the group with normal Hct than in the comparison groups (1.54 +/- 0.27 vs. 1.98 +/- 0.52 and 2.23 +/- 0.93 micromol/l; p < 0.01), but did not differ significantly between the anemic groups. GSH and GSSG concentrations corrected for erythrocyte levels showed no significant differences, but whole-blood levels in patients with Hct > or = 0.4 and 0.3 - 0.39 were significantly higher than in patients with Hct < 0.3 (GSH: 0.97 +/- 0.42 vs. 1.03 +/- 0.38 and 0.62 +/- 0.34 micromol/ml; GSSG: 14.57 +/- 6.06 vs 13.07 +/- 5.18 and 7.28 +/- 3.64 micromol/l; p < 0.05). CONCLUSION: After correction of renal anemia, MDA levels are significantly lower - reflecting decreased free radical generation - than in anemic HD patients. Whole-blood antioxidant capacity is significantly increased. Overall, rhEPO therapy has clearly positive effects on free radical metabolism.

Long-term effects of rhEPO therapy on erythrocyte rheology in dialysis patients with different target hematocrits.

UNLABELLED: Successful treatment of renal anemia with recombinant erythropoietin (rhEPO) raises the question of whether the renal anemia symptom complex requires complete correction. Current arguments against increasing hemoglobin (Hb) levels above 10-11 g/dl are impaired hemodynamics, increased risk of vascular access occlusion, unmanageable hypertension and dialysis complications. The aim of the study was to determine whether sustained Hb normalization using long-term rhEPO causes hemorheological changes with a potentially negative hemodynamic impact. The study was conducted in 42 rhEPO-treated dialysis patients with stable Hb > 11.0 g/dl for at least 20 weeks. The mean Hb of the total study group was 12.8 1.1 g/dl. To study the effect of Hb as a risk indicator in greater detail, the patients were divided into two groups, with hematocrits above and below 0.40. Hemorheology (erythrocyte deformability and aggregation, plasma viscosity) showed no significant changes, including vs a healthy control group. Throughout the period of increased rhEPO administration, no increase was observed in the incidence of hypertension or vascular thrombosis. CONCLUSION: the marked additional quality-of-life benefit achieved by complete correction of renal anemia harbors no substantial increase in treatment risk.

Complete correction of renal anemia by recombinant human erythropoietin.

The target-hematocrit (Hct) for the correction of renal anemia by recombinant human erythropoeitin (rhEPO) therapy is discussed controversially. A normalization of the Hct that could lead to a further improvement of the patients status, is often rejected, because of possible side effects as a result of an increase in blood viscosity. Hemodialysis (HD) induces an acute hemoconcentration due to ultrafiltration that might influence these risk factors negatively and therefore conflict with the normalization of Hct. The aim of this study was to investigate the changes in rheological and biochemical parameters in chronic HD patients with a normal initial Hct before hemodialysis. Results in 39 patients are given as mean +/- SD before/after HD: Hct 0.42 +/- 0.05/0.45 +/- 0.05 (p < 0.001), hemoglobin (g/dI) 13.3 +/- 1.0/14.4 +/- 1.3 (p < 0.001), MCV (fl) 99.3 +/- 5.7/99.1 +/- 5.5, MCHC (mM/l) 19.9 +/- 0.6/20.1 +/- 0.6 (p < 0.01), red blood cell (RBC) elongation (%) 60.97 +/- 3.67/60.99 +/- 3.73, RBC aggregation index AI0 0.52 +/- 0.12/0.50 +/- 0.12, AI4 0.52 +/- 0.14/0.51 +/- 0.12, plasma viscosity 1.74 +/- 0.14/1.92 +/- 0.20 (p < 0.001), whole blood viscosity (WBV), etaabs.100(mPas) 5.91 +/- 0.78/6.80 +/- 1.2 (p < 0.001), etaabs.0.01(mPas) 75.81 +/- 35.48/167.656 +/- 98.686 (p < 0.05), ultrafiltration (FM) 2.1 +/- 1.1. The biochemical parameters protein, albumin, IgG, IgA, IgM, cholesterol, transferrin and fibrinogen are significantly increased after HD. The hemoconcentration during HD is associated with a significant increase in WBV, mainly associated with the increase in Hct (r = 0.83), but not exceeding the normal range compared to healthy controls. The increase in plasma viscosity is correlated mainly with an increase in protein (r = 0.80), albumin (r = 0.74), and fibrinogen (r = 0.54). No significant changes in RBC aggregation and deformability were observed during the HD session. In conclusion, from the rheological point of view it is unlikely that the normalization of the Hct will contribute to an increased risk in access thrombosis or thromboembolic events in HD patients.

How can hemodialysis-associated hypotension and dialysis-induced symptoms be explained and controlled--particularly in diabetic and arteriosclerotic patients?

Patients with diabetes and/or severe arteriosclerosis are often unable to tolerate volume removal during hemodialysis (HD) and develop hemodialysis-induced symptoms. These problems can be omitted by well-balanced correction of the acid/base status. We compared 20 high-risk patients which were either treated with standard HD (dialysate bicarbonate 33 mmol/l, treatment A) or treated with standard HD and additional administration of NaHCO3 (120-160 ml 8.4% NaHCO3 solution over the venous line during HD) to correct the metabolic acidosis to upper normal values (treatment B). The following parameters were compared: 1. Acid/base status; 2. EEG monitoring and clinical observation of dialysis-induced symptoms; 3. Invasive monitoring of circulation by Swan-Ganz thermodilution; 4. Ventilation, oxygen consumption and lactate production. Optimal correction of acid/base values resulted in symptom-free hemodialysis sessions with stable PaCO2 in the normal range, cardiovascular stability assessed by invasive monitoring, normal ventilation and higher oxygen consumption and decreased lactate production. Optimal correction of acid/base balance further led to the absence of EEG alterations and of dialysis-induced symptoms during treatment B as compared to treatment A. The baroreceptor response in these patients is usually disturbed due to sclerosis of the pressosensible vessels, especially the aortic arch and the pulmonary arteries impairing a compensatory increase of heart rate upon volume removal. However, chemoreceptors are able to increase sympathetic tone with preservation of blood pressure in this situation. In addition a decrease of PaO2 during volume removal can only be answered by an early increase of ventilation response due to stimulation of chemoreceptors provided that PaCO2 is maintained normal. Furthermore, normal cerebral blood flow also depends on a normal PaCO2. Based on these pathophysiological mechanisms the therapeutic strategy of additional bicarbonate administration to correct the acid/base status guarantees a stable normal PaCO2 and facilitates a symptom-free HD in high-risk patients.

Cardiac mortality prevention in uremic patients. Therapeutic strategies with particular attention to complete correction of renal anemia.

BACKGROUND: Left ventricular hypertrophy represents the major risk factor for cardiac mortality and morbidity, with cardiac mortality being the most important determinant for survival in dialysis patients. The prevalence of left ventricular hypertrophy is already high at initiation of dialysis and increases with time. Anemia is considered as the most important factor for the development of left ventricular hypertrophy. Others already demonstrated that with partial correction of renal anemia by erythropoietin a partial regression of the left ventricular mass can be achieved. PATIENTS AND METHODS: We investigated the effect of complete correction of renal anemia to normal hemoglobin values of 14 g/dl (Hct 42%) on left ventricular hypertrophy by echocardiography. Eight Patients entered the study 4-8 weeks after initiation of chronic hemodialysis with a mean hemoglobin of 9.5 +/- 1.3 g/dl). RESULTS: Left ventricular mass index (LVMI) decreased from 155 +/- 45 g/m2 to 123 +/- 18g/m2 (p < 0.05) within the observation period of 12 +/- 5 months. The results showed, that either normal left ventricular dimensions could be preserved or, if left ventricular hypertrophy was already present, complete regression was possible. CONCLUSION: Therefore, we propose that complete correction of renal anemia should be introduced into the therapy of dialysis patients along with strict adherence to established measures for the control of left ventricular hypertrophy: control of fluid overload and arterial hypertension and the use of ACE-inhibitors and betablockers. In addition, optimal correction of metabolic acidosis, control of the calcium-phosphate product and hyperparathyreoidism must be attempted. Thus, it should be possible to reverse left ventricular hypertrophy and its deleterious consequences in the dialysis population in order to improve survival and quality of life.

In vitro biocompatibility evaluation of a novel bicarbonate-buffered amino-acid solution for peritoneal dialysis.

BACKGROUND: Conventional lactate-buffered peritoneal dialysis fluids containing glucose as the osmotic agent have been shown to compromise important peritoneal host defence functions. The current study employed an in vitro model using activated peripheral blood mononuclear leukocytes (PBMC) for the preclinical biocompatibility assessment of a novel bicarbonate-buffered peritoneal dialysis fluid containing 1.0% amino acids as the osmotic agent. METHODS: PBMC (5 x 10(6)/ml) were pre-exposed (10-30 mm, 37 degrees C) to bicarbonate-buffered 1% amino-acid solution, bicarbonate- or lactate-buffered 1.5% glucose fluid, or control medium (RPMI). The cells were then washed and stimulated for 2 h at 37 degrees C in RPMI containing 100 ng/ml E.coli endotoxin from strain O55:B5. The cytokines IL-6 and TNF alpha in cell supernatants were assessed using specific enzyme immunoassays, cytokine mRNA expression by reverse transcription polymerase chain reaction. RESULTS: Short, i.e. 10 min, exposure to conventional, lactate-buffered glucose fluid resulted in a significant and time-dependent inhibition of cytokine release and mRNA expression by activated PBMC, whereas the cytokine response was improved even following prolonged (up to 2 h) exposure to bicarbonate-buffered 1% amino-acid solution or bicarbonate-buffered 1.5% glucose fluid. CONCLUSIONS: Our results suggest that very short, i.e. potentially clinically relevant, exposure to conventional dialysis fluid impairs the cytokine response by activated leukocytes. In this respect, the use of bicarbonate-buffered solutions containing 1.0% amino acids or 1.5% glucose may result in improved biocompatibility properties.

Establishment and functional characterization of human peritoneal fibroblasts in culture: regulation of interleukin-6 production by proinflammatory cytokines.

The functional and morphologic integrity of the peritoneal membrane is of major importance for the successful treatment of patients with chronic peritoneal dialysis. This study aimed at the establishment and functional characterization of human peritoneal fibroblasts (HPFB) in cell culture. HPFB were isolated from human omentum by enzymatic digestion and cultured. Confluent HPFB could be identified as spindle-shaped cells, growing in parallel arrays and whorls which stained positive for vimentin and negative for factor VIII, cytokeratin 18, and desmin. Maximum cell growth was observed after 24 h in medium supplemented with 10% fetal calf serum. HPFB could be growth arrested and maintained in fetal calf serum-depleted medium (0.1%) for > 48 h without loss of cell viability as evaluated by intracellular ATP determination. Stimulation of resting HPFB for 0.5 to 48 h with increasing doses of interleukin (IL)-1 beta and/or tumor necrosis factor-alpha (1 to 10,000 pg/mL) resulted in a dose- and time-dependent induction of IL-6 messenger RNA and an increase in immunoreactive IL-6 protein secreted into HPFB supernatants, which was significant with IL-1 beta or tumor necrosis factor-alpha doses as low as 1 pg/mL. HPFB IL-6 production could be inhibited by both actinomycin D or cycloheximide, which suggests that the induction of IL-6 occurs both on a transcriptional and a post-transcriptional level. In summary, this cell culture model is expected to facilitate further investigation of the potential role of the HPFB in the peritoneal cytokine network of patients treated with chronic peritoneal dialysis.

In-vitro biocompatibility of alternative CAPD fluids; comparison of bicarbonate-buffered and glucose-polymer-based solutions.

Evidence is accumulating that conventional dialysis fluids for CAPD are incompatible with peritoneal host defence. We therefore investigated the effect of alternative CAPD fluids on mononuclear leukocyte (PBMC) viability and cytokine production in vitro. Fluids tested were bicarbonate-buffered solutions containing 1.5% or 4.25% glucose, 7.5% glucose polymer dialysis fluid (GPDF), and conventional 1.5% glucose fluid (G1.5%). PBMC were stimulated (2 h, 37 degrees C) in the different test fluids with a clinical isolate of Staphylococcus epidermidis or Escherichia coli lipopolysaccharide. The cytokines TNF alpha and IL-6 in PBMC supernatants were measured by specific enzyme immunoassays. Induction of cytokine messenger RNA was evaluated by reverse transcription-polymerase chain reaction. Conventional G1.5% (pH 5.5) inhibited cytokine release from activated PBMC by > 95%, whereas cell responses in low-glucose bicarbonate fluid were not significantly reduced. In contrast, high-glucose bicarbonate fluid exerted > 80% inhibition despite its neutral pH. GPDF was inhibitory at its initial low pH, whereas cytokine release was restored following pH neutralization. Cytokine mRNA expression was suppressed by conventional G1.5% fluid and by high-glucose bicarbonate fluid. These data indicate that pH neutralization leads to a substantial improvement of dialysis fluid biocompatibility; however, hyperosmolality and/or high glucose content inhibit cell responsiveness even at normal pH. Replacement of glucose by glucose polymer might prove beneficial provided that the initial low pH is neutralized.