A comparison of solute clearance and ultrafiltration volume in peritoneal dialysis with total or fractional (50%) intraperitoneal volume exchange with the same dialysate flow rate

Background: The most efficient way to perform automated peritoneal dialysis (APD) has not yet been defined. Tidal peritoneal dialysis (TPD) has been claimed to be more efficient than traditional intermittent peritoneal dialysis (IPD), but few comparative studies have been done keeping dialysate flow the same in the two treatment techniques. Method: Six patients were treated with 10, 14 and 24 litres total dialysis fluid volume during 9 h (flow rate 18,5, 25.9 and 44.4 ml/min), receiving the treatments both as IPD and TPD. Glucose concentration in the fluid was held constant during all treatments. Transperitoneal clearances (ml/min) for urea, creatinine and uric acid and ultrafiltration volume was calculated, and comparisons made between TPD and IPD. The total intraperitoneal dwell time was calculated for each treatment session. A peritoneal equilibration test was also done for each patient. Results: The ratio of the creatinine concentration in dialysate to the concentration in plasma at 4 h obtained with the peritoneal equilibration test (PET) averaged 0.77 (range 0.69-0.82). Urea clearance was higher for IPD than for TPD with 10 litres: 14.3±2.4 and 13.3±2.7 (P=0.0092). For 14 and 24 litres urea clearance for IPD and TPD was 17.9±2.3 and 15.9±3.5 (n.s.) and 20.9±3.6 and 19.9±5.6 (n.s) respectively. Creatinine clearance was higher for IPD than for TPD with 10 litres: 9.6±1.3 and 8.9±1.3 (P=0.0002). For 14 and 24 litres creatinine clearance for IPD and TPD was 11.0±0.7 and 9.9±2.0 (n.s.) and 12.3±1.2 and 12.4±2.2 (n.s.) respectively. Uric acid clearance was higher for IPD than for TPD with 10 litres: 8.4±1.3 and 7.7±1.0 (p=0.0054). For 14 and 24 litres uric acid clearance for IPD and TPD was 9.4±1.7 and 8.9±2.2 (n.s.) and 11.3±2.9 and 10.6±2.6 (n.s.) respectively. IPD gave significantly higher ultrafiltration volume (ml) than IPD for both 10 and 14 litres: 944±278 and 783±200 (P=0.0313) and 1147±202 and 937±211 (P=0.0478). For 24 litres there was no significant difference between IPD and TPD: 1220±224 and 1253±256. Conclusion: With the lowest dialysate flow rate (18.5 ml/min), solute clearance and ultrafiltration volume was higher on IPD than on TPD. With the intermediate flow rate (25.9 ml/min) the ultrafiltration volume was higher on IPD, but no difference was found for solute clearance. With the highest flow rate (44.4 ml/min) there as no difference neither for ultrafiltration nor for solute clearance.     

Does long-term treatment of renal anaemia with recombinant erythropoietin influence oxidative stress in haemodialysed patients?

Background. Patients with end-stage renal failure undergoing haemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) were demonstrated in plasma of uraemic patients, indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients. Methods. MDA and 4-hydroxynonenal (HNE) were measured in three groups of patients undergoing HD: group I comprised eight patients with a blood haemoglobin (Hb) <10 g/dl (mean Hb=8.1±1.3 g/dl), and group II were eight patients with a Hb <10 g/dl (mean Hb=12.4±1.9 g/dl); none of these 16 patients had been treated with human recombinant erythropoietin (rHuEpo). Group III comprised 27 patients with a mean Hb of 10.5±1.6 g/dl after long-term rHuEpo treatment. Results. Mean plasma concentrations of both MDA and HNE were significantly higher (P<0.0001) in all 43 HD patients than in 20 healthy controls (MDA 2.85±0.25 vs 0.37± &mgr;M, HNE 0.32± vs 0.10±0.01 &mgr;M). Comprising the three groups, it was shown that HD patients with a Hb <10 g/dl had significantly higher plasma levels of LPO products (MDA 3.81±0.86 &mgr;M, HNE 0.45±0.07 &mgr;M) than HD patients with a Hb > 10 g/dl (MDA 2.77±0.58 &mgr;M, HNE 0.25±0.05 &mgr;M), and than HD patients treated with rHuEpo (MDA 2.50±0.12 &mgr;M, HNE 0.29±0.03 &mgr;M). Furthermore, an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen (r=0.62, P<0.0001). Conclusion. 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. Keywords: erythropoietin; haemodialysis; HNE; lipid peroxidation; MDA; renal anaemia      

Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study

Background: Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. Study design: In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. Results: Serum bicarbonate levels and arterial pH increased respectively from 19.3±0.6 mmol/l to 24.4±1.2 mmol/l (P<0.0001) and 7.34±0.03 to 7.40±0.02 (P<0.0001). Serum albumin increased from 34.9±2.1 g/l to 37.9±2.9 g/l (P<0.01) while PCRn decreased from 1.11±0.17 g/kg/day to 1.03±0.17 g/kg/day (P<0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. Conclusions: Our data demonstrate that correction of metabolic acidosis improves serum albumin concentration in HD patients. The correction of acidosis induced a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.     

Regression of left ventricular hypertrophy in haemodialysis patients by ultrafiltration and reduced salt intake without antihypertensive drugs

Background: Left ventricular hypertrophy (LVH) is very frequent in haemodialysis patients. Only few investigations have reported its regression, and only by the use of antihypertensive drugs. Because volume load is at least as important as pressure load, we investigated whether persistent strict volume control by ultrafiltration alone may be effective in improving LVH. Methods: Using blood pressure (BP) and cardiac dimensions as a guide, we treated all hypertensive patients in our dialysis unit during the 3 times weekly dialysis sessions for 4 h per session with as much ultrafiltration as they could stand. If they gained too much weight an extra isolated ultrafiltration (UF) session was applied. Special attention was given to dietary salt restriction. The study group of all 15 patients in whom echocardiographic assessment had been made at least 1.5 years previously was selected retrospectively, and we acknowledge that important confounding factors might not have been controlled for. Cardiothoracic index (CTI) was estimated on the chest X-ray. Diameters of left atrium (LA), left ventricle systolic (LVS) and diastolic (LVD), interventricular septum (IVS), posterior wall (PW), and left ventricular mass index (LVMI) were estimated by standard echocardiographic methods. Results: Mean arterial pressure of the study group had been lowered by UF before the first echocardiogram from predialysis 136±11 to 101±14 and from post dialysis 119±8 to 92±12 mmHg. During a mean follow-up period of 37±11 months LVMI decreased from 175±60 to 105±11 g/m². CTI decreased further from 48±3 to 43±4%, while significant decreases of LA (22.5±3 to 19.9±4 mm/m²), LVS (18.7±4 to 15.9±3 mm/m²) and LVD (28.3±4 to 24.0±3 mm/m²) were seen in all patients. There also was a further decrease in both pre- and postdialysis BP to 116±12/73±7 and 105±7/65±3 mmHg respectively. Conclusion: The results of this uncontrolled retrospective study suggest that good long-term BP control and a decrease of LVM can be achieved by continuous efforts to control hypervolaemia. The decrease in volume may be even more important than pressure reduction to achieve this goal.     

Impact of gender and dialysis adequacy on anaemia in peritoneal dialysis

Purpose

In the general population, haemoglobin (Hb) concentration is higher in men than in women. However, target Hb levels in dialysis patients are set constant regardless of the patient’s sex. The aim of this study was to evaluate Hb concentration and the use of erythropoiesis-stimulating agents (ESA) in peritoneal dialysis (PD) patients taking gender and dialysis adequacy into account.

Methods

The study comprised two parts. The first was a cross-sectional analysis of Hb and ESA in 2180 prevalent PD patients. The second included 88 incident PD patients, followed for 36 months. During this time, the major parameters recorded at 12-month intervals included: Hb concentration, weekly ESA, total, renal, and peritoneal Kt/V. Erythropoietin resistance index (ERI) was calculated as the ratio between ESA dose and achieved Hb.

Results

In prevalent PD patients, Hb concentration was significantly lower in women, (11.2 ± 1.4 vs. 11.5 ± 1.6 g/dl; p < 0.001), despite higher doses of ESA (2691 ± 1821 vs. 2344 ± 1422; p = 0.001). Hb concentrations were related to dialysis adequacy in both cohorts. However, despite significantly higher Kt/V, women were characterized by a lower Hb level. In incident patients, this association was present throughout the observation period, while the ESA dose in women was significantly higher at every time point. In multiple regression analysis, gender was an independent determinant of ERI (b = 0.34; p < 0.05).

Conclusions

Despite higher dialysis adequacy, Hb concentration in women treated with PD is significantly lower, and the ability to correct it impaired, as compared to men.

     

Oxidative damage of red blood cells in haemolytic uraemic syndrome

Changes in red blood cell (RBC) lipid peroxidation [measured by malonyl dialdehyde (MDA) concentration], glutathione (GSH) metabolism, antioxidant enzyme activities (catalase, superoxide dismutase, glutathione peroxidase) and haemoglobin (Hb) metabolites (metHb, carboxy Hb) were studied in six children with post-enteropathic (D+) haemolytic uraemic syndrome (HUS) and ten controls. The in vitro effect of hydrogen peroxide [acetyl-phenylhydrazine (APH) test] on GSH and Hb metabolism was also investigated. MDA levels were significantly higher and the antioxidant enzyme activities were lower in HUS patients than in the controls (P<0.01). The oxidised glutathione concentration was significantly higher in the patients than in the control children (26.3±12.6 vs. 10.9±1.8 nmol/g Hb. Percentage values of carboxy Hb and metHb were also higher in HUS (P<0.01). Incubation of RBC with APH induced a more pronounced decrease in the concentration of GSH (P<0.001) and a significant increase (P<0.01) in the level of metHb and carboxy Hb in the HUS patients. This suggests that there is reduced RBC GSH stability in HUS. Utilisation of GSH and antioxidant enzymes leads to increased Hb oxidation and haemolysis. The oxidative damage may have an important role in the pathogenesis of haemolytic anaemia in HUS.     

High and low sodium acetate haemodialysis and ultrafiltration

This study was undertaken to evaluate the effect of increasing the dialysate sodium concentration on haemodynamic effects, arterial blood gases and chemistries during haemodialysis and ultrafiltration. Significant changes in mean blood pressure (MBP) and heart rate (HR) were not noted; but significant differences in sodium, potassium, total protein concentration, haematocrit and plasma osmolality during dialysis and ultrafiltration were found with both dialysates. Significant differences were also noted in pCO₂ during dialysis and ultrafiltration with both dialysates and increase of pH during dialysis with low sodium dialysate. Significant changes in kind and frequency of unpleasant symptoms were found with both dialysates.     

Online measurement of haemoglobin concentration.

BACKGROUND: Regular monitoring of haemoglobin in chronic haemodialysis patients is essential to ensure that targets for anaemia management are consistently achieved. Repeated blood sampling can be time consuming, invasive and, for pragmatic reasons, only infrequently performed, often delaying therapeutic change. On-line optical continuous monitoring of the haemoglobin concentration would allow non-invasive assessment of haemoglobin, and immediate therapeutic changes could be implemented, thereby improving the efficiency of anaemia management. This study aimed to evaluate the use of on-line haemoglobin concentration measurement. METHODS: Eleven dialysis monitors (Integra Hospal) were calibrated using at least five haemoglobin samples spread over at least 4 g/dl. Optical measurement of haemoglobin concentration is already incorporated into the dialysis monitor to allow the study of relative blood volume. Fifteen patients were studied with paired haemoglobin measurements (i.e. dialysis monitor value and conventional laboratory assessment) taken at intervals over 7 months (mean 11.0+/-0.28 g/dl, range 7.5-14.8). RESULTS: Haemoglobin measured by Hemoscan correlated well with the laboratory measurements (r2 = 0.83, P<0.0001), indicating that the machine values are broadly comparable with laboratory figures. There was a mean underestimate of haemoglobin by Hemoscan of 0.34%. There was no significant deterioration in the quality of this correlation over the study period (r2>0.8). CONCLUSION: The ability of the dialysis monitor to measure the optical concentration of haemoglobin compared with conventional laboratory assessment is both precise and accurate. Regular on-line assessment of haemoglobin may allow more proactive micromanagement of renal anaemia, with a reduction in the time taken to achieve clinically important targets and give early warning of suboptimal response to treatment.     

The effect of erythropoietin on the cellular defence mechanism of red blood cells in children with chronic renal failure

The glutathione redox system, haemoglobin (Hb) oxidation, the activity of antioxidant enzymes and the lipid peroxidation product malonyl dialdehyde (MDA) were studied in red blood cells (RBCs) during administration of recombinant human erythropoietin (rhEPO) over 12 weeks in ten children maintained on haemodialysis. A rapid increase in the reticulocyte count was accompanied by a slower rise in total Hb concentration. The mean level of oxidized glutathione (GSSG) increased from 13.2±5.3 nmol/g Hb to 56.7±15.8 nmol/g Hb 4 weeks after the start of rhEPO (P<0.001), followed by a fall to the basal value. Reduced glutathione (GSH) levels showed a smaller though constant elevation during rhEPO therapy (P<0.001). Before rhEPO treatment, incubation of RBCs for 1 h with acetylphenylhydrazine induced a decrease in GSH concentration compared with controls (P<0.001), which became more pronounced in the first few weeks of rhEPO therapy (P<0.001). In addition, the percentage of Hb derivatives (metHb and haemichrome) increased in the first 4 weeks of rhEPO therapy (P<0.001). Although there was no significant difference between the values obtained preEPO and during EPO treatment, MDA levels were continuously higher and superoxide dismutase, catalase and glutathione peroxidase concentrations were lower than in the controls (P<0.001). These results are compatible with oxidative damage to the RBCs in the early period of rhEPO therapy in children with end-stage renal failure. The GSH-GSSG system, as an important cellular defence mechanism of the RBCs, appears to be severely affected.     

Daily home haemodialysis in the Netherlands; effects on metabolic control, heamodynamics, and quality of life

Background: More frequent dialysis has been claimed to improve clinical outcome and quality of life. Methods: Clinical status was optimized in 13 haemodialysis patients during a run-in period of 2 months with three dialysis sessions a week. Thereafter, daily home haemodialysis (DHHD, 6 sessions per week) was initiated. The total weekly dialysis dose (Kt/V) was kept constant. Results: Weekly Kt/V was 3.2±0.13 (M±SEM) before, and 3.2±0.15 after 6 months of DHHD (NS), time averaged concentration of urea (TACu) was 21.2±1.6 mmol/l and 20.1±0.9 mmol/l (NS). Urea reduction was 0.56±0.05 before DHHD, and 0.41±0.06 during DHHD (P<0.0001). Serum K remained unchanged, but significantly less exchange resins were used (P<0.02). Also, the dose of phosphate-binding agents could be decreased. Values for Na, K, Cl, bicarbonate, Ca, PTH, albumin, and Hb remained unchanged. Iron deficiency developed in some patients. Twenty-four-hour blood pressure monitoring showed a decrease of systolic blood pressure (141.1±17.2 mmHg before, and 130.9±19.2 mmHg during DHHD, P<0.001). Diastolic blood pressure remained constant (82.8±7.2 and 76.9±10.1 mmHg, NS). Mean arterial pressure decreased from 102.2±9.5 to 94.9±1.4 mmHg (P<0.02). Blood pressure decreased mainly in previously hypertensive patients. Mean target weight increased 0.8 kg. The amount of antihypertensive drugs used decreased from 1.88±0.35 to 0.75±0.17 (P<0.005, n=7). Dialysis sessions were much more stable, also in patients with cardiac insufficiency. Quality of life questionnaires (Rand 36, Nottingham Health Profile, Uraemic Symptoms Profile) showed a significant improvement of physical condition and fewer uraemic symptoms. Conclusion: DHHD compared to conventional thrice-weekly haemodialysis with similar weekly Kt/V results in an improved haemodynamic control and quality of life, but has lesser impact on metabolic regulation.