Reduced survival and quality of life following return to dialysis after transplant failure: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Although dialysis after kidney transplant failure (TF) is common, the outcomes of these patients remain unclear. We compared outcomes of TF patients with transplant-naïve (TN) patients wait-listed for kidney transplantation. METHODS: We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), including laboratory markers and health-related quality of life (HR-QOL). Mortality and hospitalization of participants with one prior TF versus TN patients were compared using the Cox regression analysis. HR-QOL physical and mental component summary scores (PCS and MCS) were examined using linear mixed models, and clinical practices were compared using logistic regression. RESULTS: Compared with TN patients (n = 2806), TF patients (n = 1856) were younger (48 versus 51 years, P = 0.003), less likely to be diabetic (18 versus 27%, P < 0.0001) and to use a permanent surgical vascular access {adjusted odds ratio (AOR): 0.85 [95% confidence interval (CI): 0.70-1.03], P = 0.10}, particularly within the first 3 months after TF [AOR 0.45 (0.32-0.62), P < 0.0001]. TF patients also had lower PCS [mean difference -2.56 (-3.36, -1.75), P < 0.0001] but not MCS [-0.42 (-1.34, 0.50), P = 0.37]. All-cause mortality [adjusted hazard ratio (AHR): 1.32 (95% CI: 1.05-1.66), P = 0.02], especially infection-related [AHR 2.45 (95% CI: 1.36-4.41), P = 0.01], was higher among TF patients. CONCLUSIONS: TF patients have reduced QOL and higher mortality, particularly due to infections, than TN patients. Interventions to optimize care before and after starting dialysis remain to be identified and applied in clinical practice.

Achievement of recommended treatment targets for bone and mineral metabolism in haemodialysis patients using paricalcitol: an observational study.

OBJECTIVE: Secondary hyperparathyroidism (SHPT) is a common problem among patients with chronic kidney disease (CKD) on haemodialysis. This study was conducted to assess the use, effectiveness and safety of intravenous paricalcitol in haemodialysis patients with various degrees of SHPT. MATERIAL AND METHODS: This observational, multicentre, prospective study was conducted in 14 Swedish dialysis centres from May 2007 to June 2008 and included 92 haemodialysis patients with a diagnosis of SHPT associated with CKD. The decision to initiate treatment with intravenous paricalcitol was made by the treating physician. No treatment algorithms were provided. RESULTS: Mean patient age was 64 years. Of the 92 patients included, 74 had an intact parathyroid hormone (iPTH) level of >300 pg/ml at baseline. Median iPTH was 584 pg/ml in patients with a baseline PTH of >300 pg/ml. During follow-up there was a decrease in iPTH to 323 pg/ml at 6 months (-45%, p < 0.0001). In parallel, there was a small increase in serum calcium, but serum phosphorus and the calcium × phosphorus product remained unchanged. CONCLUSIONS: This study showed that intravenous paricalcitol substantially and safely decreased iPTH in haemodialysis patients with a baseline iPTH above the Kidney Disease Outcomes Quality Initiative recommended target range (150-300 pg/ml) and had minimal impact on serum minerals.

MDCT angiography with 3D image reconstructions in the evaluation of failing arteriovenous fistulas and grafts in hemodialysis patients.

BACKGROUND: Arteriovenous fistulas and grafts are the methods of choice for vascular access in renal failure patients in need of hemodialysis. Their major complication, however, is stenosis, which might lead to thrombosis. PURPOSE: To demonstrate the usefulness of 16-MDCTA with 3D image reconstructions, in long-term hemodialysis patients with dysfunctional arteriovenous fistulas and grafts (AVF and AVG). MATERIAL AND METHODS: During a 17-month period, 31 patients with dysfunctional AVF and AVG (24 AVF and seven AVG) were examined with MDCTA with 3D image postprocessing. Parameters such as comprehension of the anatomy, quality of contrast enhancement, and pathological vascular changes were measured. DSA was then performed in 24 patients. RESULTS: MDCTA illustrated the anatomy of the AVF/AVG and the entire vascular tree to the heart, in a detailed and comprehensive manner in 93.5% of the evaluated segments, and depicted pathology of AVF/AVG or pathology of the associated vasculature. MDCTA demonstrated a total of 38 significant stenoses in 25 patients. DSA verified 37 stenoses in 24 patients and demonstrated two additional stenoses. MDCTA had thus a sensitivity of 95%. All 24 patients were treated with percutaneous transluminal angioplasty (PTA) with good technical results. CONCLUSION: MDCTA with 3D reconstructions of dysfunctioning AVFs and AVGs in hemodialysis patients is an accurate and reliable diagnostic method helping customize future intervention.

Dialysis Outcomes and Practice Patterns Study estimate of patient life-years attributable to modifiable haemodialysis practices in Sweden.

OBJECTIVE: To examine the association of adherence to Swedish Society of Nephrology guidelines on haemodialysis treatment and patient outcomes in Sweden. MATERIAL AND METHODS: A prevalent cross-sectional sample of Swedish haemodialysis patients was obtained from the Dialysis Outcomes and Practice Patterns Study (DOPPS II, 2002-2004), an international, prospective, cohort study that investigates relationships between patient outcomes and haemodialysis practices. The sample was used to estimate life-years gained through adherence to six potentially modifiable practice patterns: dialysis dose, anaemia, serum phosphorus, serum calcium, serum albumin and catheter use for vascular access. Cox proportional hazards regression models were used to calculate the relative risk of mortality for all patients outside each guideline. RESULTS: The practices resulting in the largest patient-year gains were increasing patient albumin above 35 g/l and reducing facility catheter use to below 10%. Compliance with the albumin target levels could save approximately 441 life-years (or as many as 904 years). Similarly, by 2010, 409 life-years (or as many as 837 years) could be saved if vascular access target levels were achieved. CONCLUSION: The analysis suggests potential opportunities to improve haemodialysis patient care in Sweden. Estimates of life-years saved may serve as motivation for the improvement of patient care through adherence to published guidelines supported by international data from the DOPPS.

Subgroups of haemodialysis patients in relation to fluid intake restrictions: a cluster analytical approach.

AIMS: To determine whether definable subgroups exist in a sample of haemodialysis patients with regard to self-efficacy, attentional style and depressive symptomatology and to compare whether interdialytic weight gain varies between patients in groups with different cognitive profiles. BACKGROUND: Theory-based research suggests that cognitive factors (e.g. self-efficacy and attentional style) and depressive symptomatology undermine adherence to health protective regimens. Preventing negative outcomes of fluid overload is essential for haemodialysis patients but many patients cannot achieve fluid control, and nursing interventions aimed to help the patients reduce fluid intake are ineffective. Understanding the interaction between cognitive factors and how this is related to adherence outcomes might therefore lead to the development of helpful nursing interventions. DESIGN: Explorative cross-sectional multicentre survey. METHODS: The sample consisted of 133 haemodialysis patients. Data were collected using structured questionnaires. A brief self-report form and data on interdialytic weight gain was also used. Two-step cluster analysis was used to identify subgroups. One-way analysis of variance (anova) or Pearson's chi-square test was used for comparing subgroups. RESULTS: Three distinct subgroups were found and subsequently labelled: (1) low self-efficacy, (2) distraction and depressive symptoms and (3) high self-efficacy. The subgroups differed in fluid intake, but not in age, dialysis vintage, gender, residual urine output or in receiving any fluid intake advice. CONCLUSIONS: Clinically relevant subgroups of haemodialysis patients could be defined by their profiles regarding self-efficacy, attentional style and depressive symptoms. RELEVANCE TO CLINICAL PRACTICE: Based on this study, we would encourage clinical practitioners to take into account cognitive profiles while performing their work. This is especially important when a targeted nursing intervention, which aims to encourage and maintain the patient's fluid control, is introduced.

Comorbidity and acute clinical events as determinants of C-reactive protein variation in hemodialysis patients: implications for patient survival.

BACKGROUND: Patients with chronic kidney disease stage 5 have high comorbidity and are prone to inflammation that may contribute to the high cardiovascular mortality risk. STUDY DESIGN: Three-month observational cohort study of prevalent hemodialysis patients. SETTINGS & PARTICIPANTS: 228 hemodialysis patients (44% women) were included, median age of 66 years, median time on dialysis therapy of 29 months. PREDICTORS & OUTCOMES: In part 1, comorbidity and intercurrent illness were predictors and C-reactive protein (CRP) level was the outcome. In part 2, serial CRP values were predictors and survival was the outcome. MEASUREMENTS: High-sensitivity CRP was measured weekly and interleukin 6 (IL-6), tumor necrosis factor alpha, and IL-10 were measured monthly. Data for comorbidity were collected from patient records to calculate Davies comorbidity score, and self-reported clinical events were recorded weekly. RESULTS: Median baseline CRP level was 6.7 mg/L (25th to 75th percentiles, 2.5 to 21 mg/L). Baseline CRP level correlated with time-averaged CRP (Spearman rho = 0.76) and individual median of serial CRP values (rho = 0.78; both P < 0.001). Part 1: comorbidity score was significantly associated with greater CRP and IL-6 levels. Age, sex, comorbidity, and 7 of 12 clinical events had significant effects on CRP level variation. Part 2: during a mean follow-up of 29 months, 38% of patients died. Median and mean serial CRP levels were associated with a greater hazard ratio for death (1.013; 95% confidence interval, 1.004 to 1.022) and 1.012 (95% confidence interval, 1.004 to 1.020) than baseline, maximum, and minimum CRP values during the study. Other significant covariates were age, Davies risk group, dialysis vintage, and albumin level. LIMITATIONS: The study is based on observational data for prevalent dialysis patients. CONCLUSIONS: Comorbidity and clinical events are strongly associated with inflammation in hemodialysis patients. Despite variability over time, inflammation assessed by using CRP level is a strong predictor of mortality. Serial measurements provide additional information compared with a single measurement.

Interdialytic weight gain and ultrafiltration rate in hemodialysis: lessons about fluid adherence from a national registry of clinical practice.

Excessive interdialytic weight gain (IWG) and ultrafiltration rates (UFR) above 10 mL/h/kg body weight imply higher morbidity and mortality. This study aimed to estimate the prevalence of high fluid consumers, describe UFR patterns, and describe patient characteristics associated with IWG and UFR. The Swedish Dialysis DataBase and The Swedish Renal Registry of Active Treatment of Uremia were used as data sources. Data were analyzed from patients aged >/=18 on regular treatment with hemodialysis (HD) and registered during 2002 to 2006. Interdialytic weight gain and dialytic UFR were examined in annual cohorts and the records were based on 9693 HD sessions in 4498 patients. Differences in proportions were analyzed with the chi-square test and differences in means were tested using the ANOVA or the t test. About 30% of the patients had IWG that exceed 3.5% of dry body weight and 5% had IWG >/=5.7%. The volume removed during HD was >10 mL/h/kg for 15% to 23% of the patients, and this rate increased during the first dialytic year. Patient characteristics associated with fluid overload were younger age, lower body mass index, longer dialytic vintage, and high blood pressure. By studying IWG and dialytic UFR as quality indicators, it is shown that there is a potential for continuing improvement in the care of patients in HD settings, i.e., to enhanced adherence to fluid restriction or alternatively to extend the frequency of dialysis for all patients, e.g., by providing daily treatment.

Abdominal aortic calcification in dialysis patients: results of the CORD study.

BACKGROUND: Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain radiographs. The present report is an analysis of baseline data on AAC in patients enrolled in the CORD (Calcification Outcome in Renal Disease) study. METHODS: A total of 47 centres in six European countries participated in this cross-sectional study. Inclusion criteria were age >or=18 years and duration of dialysis >or=3 months. Lateral lumbar radiography of the abdominal aorta was used to determine the overall AAC score, which is related to the severity of calcific deposits at lumbar vertebral segments L1-L4. The reliability of the method was tested by double reading of 64 radiographs (coefficient of correlation 0.9). RESULTS: A lateral lumbar radiograph was obtained in 933 patients. Calcification (AAC score >or= 1) was present in 81% of the patients; its severity increased significantly from L1 to L4 (P < 0.0001) and affected all of these segments in 51% of patients. Independent predictors for the presence and severity of calcification were age (odds ratio [OR] 1.103/year; P < 0.0001), duration of dialysis (OR 1.110/year; P = 0.002) and history of cardiovascular disease (OR 3.247; P < 0.0001). CONCLUSIONS: AAC detected by lateral lumbar radiograph is associated with several risk factors of uraemic calcification. This semi-quantitative method is more widely available and less expensive than the current procedures for studying calcification and could form part of a pre-transplant workup and cardiovascular risk stratification.

Heart rate variability is decreased in chronic kidney disease but may improve with hemoglobin normalization.

BACKGROUND: Cardiac autonomic function can be measured by heart rate variability (HRV). Dialysis patients have an abnormally low HRV and are at increased risk for sudden death. A reduction in HRV is associated with anemia. HRV was therefore measured in patients with chronic kidney disease (CKD) after hemoglobin normalization. METHODS: Sixteen nondiabetic patients with CKD stage 4 (glomerular filtration rate 23.7 +/- 13.9 ml/min) and renal anemia received epoetin aiming at a hemoglobin level of 135-150 g/L. HRV was measured by 24-hour Holter electrocardiogram at baseline and after hemoglobin normalization and in a reference group consisting of 16 volunteers without impairment of renal function. RESULTS: Hemoglobin level increased from 100.7 +/- 12.6 g/L to 142.4 +/- 7.2 g/L during the study. At baseline, HRV measured in the time domain as the standard deviation of all normal RR intervals in the entire 24-hour electrocardiogram (SDNN) was 116.3 +/- 39.2 ms compared with 147.5 +/- 27.2 ms in the reference group (p<0.05). The frequency domain measures low-frequency power and total power were 367.7 +/- 350.2 ms2 and 1,368.9 +/- 957.4 ms2 compared with 717.3 +/- 484.5 ms2 and 2,228.3 +/- 1142.4 ms2 (p<0.05) in the reference group. After hemoglobin normalization there was an increase in low-frequency power to 498.3 +/- 432.7 ms2 (p<0.05) and in total power to 1,731.0 +/- 1,069.4 ms2 (p<0.05) while SDNN remained at 120.9 +/- 33.8 ms (p=ns). CONCLUSIONS: CKD patients not yet on dialysis had a reduced HRV, indicating impaired autonomic function, compared with a reference group without impaired renal function. Hemoglobin normalization improved but did not fully normalize HRV. The clinical significance of this deserves further investigation.

World apheresis registry data from 2003 to 2007, the pediatric and adolescent side of the registry.

OBJECTIVES: Paediatric patients are a special group in apheresis. It is general accepted to use adult indications in paediatric patients, but data in this age group are rare. In order to provide more information of apheresis practise in children and young adults (<21a) we will report of knowledge learnt by data from the registry from 2003 until 2007. METHODS: This is a web-based registry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 12,448 procedures have been included. Six hundred and twelve procedures were performed in 135 children and young adults (308 procedures<16a, 237 from 17 to 20a, and 67 with 21a) representing 5% of the total population. The median age was 14 years (range 1-21 years), 74 male and 61 female. These data were entered by 15 centres with a frequency of in median 18 aphereses in young patients per centre (range 1-287) from 2003 to 2007. RESULTS: Main indications: haematological diseases and also nephrological, and neurological. The type of aphereses was mainly Leukapheresis (196, 33%), plasma exchange (149, 25%), photopheresis (127, 21%), and lipid aphereses (79, 13%). Blood access: peripheral vessels in 305 procedures (50%, compared to 73% in adults), central venous catheter in 239 (38%), and AV-fistula in 2% and 0.3%, and in 8 (1.31%) procedures an arterial line was used. Anticoagulation was mostly by ACD (71%), heparin (18% or the combination of both (3%). 39 adverse events (AE) were registered in 22 (=3.59%) of the procedures, mostly graded as mild. Treatment was interrupted in 14 procedures (2.29%). AE's were abdominal pain, anaphylactic shock, flush, hyper- and hypotension, nausea, vertigo, cephalea and need for sedation and technical problems with the device and problems with the venous access. The rate of AE's was similar for stem cell harvesting and for plasma exchange (4% and 4.7%, respectively). CONCLUSION: The paediatric data compared to the whole registry data set are showing that aphereses are performed as safe in paediatrics as in adults. Centres are mostly handling only a few cases younger than 21. Therefore more exchange of information and experience in paediatric apheresis is warranted.

Fluid Intake Appraisal Inventory: development and psychometric evaluation of a situation-specific measure for haemodialysis patients' self-efficacy to low fluid intake.

OBJECTIVE: Self-efficacy is an important determinant of health behaviour and reflects a person's belief about their capability to complete a given task. The relationship between self-efficacy and fluid adherence has been investigated, although limited attention has been given to measurement issues. The purpose of this study was to develop a measure of situation-specific self-efficacy for constructive fluid intake behaviour in haemodialysis patients, the Fluid Intake Appraisal Inventory (FIAI). METHODS: Items were generated from an analysis of empirical studies available in the literature and exposed to an interpretability critique before haemodialysis patients confirmed sufficiency of each item. In a multi-centre study, data from 144 haemodialysis patients were collected regarding general self-efficacy, situation-specific self-efficacy, and estimated fluid consumption. Internal consistency, criterion-related validity, and structural validity were tested. RESULTS: The FIAI was found to have high internal consistency (Cronbach alpha 0.96) and the theoretical assumptions for criterion-related validity and known-group validity were supported. Structural validity was not confirmed, however, because the theoretically hypothesized four-factor model was not the prime structure. CONCLUSION: The FIAI was revealed to have satisfactory psychometric properties. The scale may be used in research or in clinical settings to study the mediating effects of self-efficacy or to modify haemodialysis patients' fluid-intake behaviour. Although this first validity study is promising, further validation focusing on reliability and cultural validity is needed.

Improvement in central arterial pressure waveform during hemodialysis is related to a reduction in asymmetric dimethylarginine (ADMA) levels.

BACKGROUND: Cardiovascular mortality is high in hemodialysis (HD) patients. Early arterial pressure wave reflections, reflecting arterial stiffness and the endogenous nitric oxide synthesis inhibitor asymmetric dimethylarginine (ADMA) levels predict mortality in HD patients. Therefore, we aimed to study changes in ADMA levels and central arterial pressure waveform during HD. METHODS: Thirty-two chronic HD patients were studied before and after a HD session. In a subset of 22 patients without arrhythmias, pulse wave analysis was performed on radial artery (SphygmoCor). Augmentation index (AIx), defined as difference between the second and first systolic peak divided by central pulse pressure, was used as a measure of arterial stiffness. ADMA was measured in plasma with the ELISA technique. Homocysteine was measured in plasma using the EIA technique. RESULTS: HD reduced both AIx (19%; p = 0.003) and ADMA levels (17%; p < 0.001). The magnitudes of changes in AIx and ADMA during HD were correlated (r = 0.44; p = 0.045). Mean arterial pressure change was not significant. HD reduced homocysteine levels, but homocysteine was not related to ADMA or AIx. CONCLUSION: The reduction in ADMA level seen after HD was associated with improvement in the central arterial pressure waveform, suggesting involvement of nitric oxide in the regulation of arterial stiffness in HD patients.

World apheresis registry report.

UNLABELLED: The establishment of national apheresis registries has been helpful to learn about therapeutic profiles and adverse event incidences. During 2003, the World Apheresis Registry was established and centers from all countries were invited to participate to register their apheresis activities (at www.iml.umu.se/medicin). MATERIAL: In this paper, we will report and analyze the first data retrieved from three centers, in 2 European countries, that registered a total of 388 therapeutic apheresis treatments in 122 patients, 95% due to acute indications. Statistical analyses were performed using an independent Student t-test and Fisher's test. A p-value of less than 0.05 was considered significant. RESULTS: Fifty percent of the treated patients were women. The mean age of the patients was 51 years (+/-17, range 16-84) and there was no difference between genders (w 50.4, m 51.6 years). Diagnoses for treatment were mainly neurological and vasculitis. In 63% peripheral access was used with a central double lumen catheter, 22% in the jugular vein, 8% in the subclavian vein and 6% the femoral vein. Significant inter-center differences were seen in regard to the access used. The main technique used was centrifugation for conventional plasma exchange (86%), while other modes were leukapheresis, erythrapheresis, platelet apheresis, LDL-apheresis and adsorption of antibodies. Citrate was the only anticoagulant in 92%. During plasma exchange procedures using centrifugation, replacement was by albumin only (58%) or plasma, the latter often in combination with albumin (42%). Adverse events (AEs) were noted in 11% of the procedures. Patients with hypocalcaemia side effects with tingling sensations were included in those data as mild AE and as moderate AEs if they received calcium (Ca) medication. No patient died due to adverse effects. A mild AE was present in 1.8% and moderate in 8.5%. During two procedures (0.5%), the AE was considered severe and therefore the procedure was interrupted. If those with AEs due to lower calcium were removed from analyses, 6.4% had AEs. Significantly more AEs were found when plasma was used as a replacement fluid (p=0.017, RR 2.05, CI 1.17-3.60). There were no differences in the incidence of AEs between genders. The number of procedures was too small to allow sub analyses of AEs in relation to the diagnoses. Adverse events were not related to the procedure used (p=0.095). Those who received additional Ca infusion during the procedure had no AEs (40 sessions) while the others who received no prophylactic Ca had an AE on 45 occasions (p=0.0141, RR 1.116, CI 1.08-1.15). CONCLUSION: Data from the registry shows that centers have various approaches to apheresis. One can learn from each other's experience to reduce side effects and improve efficacy. From these data we noted that prophylactic Ca infusion reduced side effects.

Reduced hemodialysis adequacy after hemoglobin normalization with epoetin.

BACKGROUND: Increased hemoglobin (Hb) levels and higher blood viscosity could reduce hemodialyzer clearance. We examined hemodialysis (HD) adequacy after treatment with epoetin alfa aimed at normalizing Hb levels. METHODS: Thirty-three HD patients were randomly allocated to achieve a normal Hb level (135-160 g/L) or a subnormal (control) Hb level of 90-120 g/L. HD adequacy was assessed by Kt/V measurement. RESULTS: In the 24 evaluable patients, Hb levels reached 144 +/- 11 g/L in the normal Hb group (n=10) and 109 +/- 10 g/L in the subnormal group (n=14). Single-pool Kt/V decreased from 1.25 +/- 0.19 to 1.15 +/- 0.13 (p<0.01) in the normal Hb group, but remained constant in the subnormal group (1.26 +/- 0.26 and 1.26 +/- 0.28). CONCLUSIONS: Normalization of Hb with epoetin alfa in HD patients resulted in a slight but statistically significant reduction in Kt/V. Therefore, when Hb is normalized, an increased dialysis dose could be necessary to maintain dialysis adequacy.

Health-related quality of life in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Health-related quality of life (HRQOL), a validated system of measuring patients' physical, mental, and social well-being, can be of particular use in populations with chronic conditions, such as end-stage renal disease (ESRD). METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS) has used the Kidney Disease Quality of Life Short Form (KDQOL-SF) to measure ESRD patients' self-assessment of functioning and well-being, as measured by 3 component scores: physical component summary (PCS, 4 subscales), mental component summary (4 subscales), and kidney disease component summary (11 subscales). Several DOPPS studies examined HRQOL's associations with mortality and hospitalization by country, ethnicity (United States only), and in comparison with serum albumin levels; international variations in HRQOL of ESRD patients were also evaluated. RESULTS: Lower scores for all 3 summary scores were strongly associated with higher risk of death and hospitalization; these measures, especially PCS, may better identify patients at risk for death and hospitalization than serum albumin level. Japanese patients reported a greater burden of kidney disease but higher physical functioning than patients in Europe or the United States; many other significant regional differences in HRQOL were found. In the United States, all summary scores were significantly associated with mortality risk, regardless of ethnicity. Compared with whites, blacks had higher scores for all 3 summary scores, Asians and Hispanics had higher PCS scores, and Native Americans had lower mental component summary scores. CONCLUSION: Among ESRD patients, HRQOL displays an important predictive power for adverse events. Identifying effective interventions to improve the HRQOL of patients with ESRD should be viewed as a valued health care goal.

Varying intervals of subcutaneous epoetin alfa in hemodialysis patients.

BACKGROUND: The optimal subcutaneous (SC) epoetin alfa strategy is unestablished. The individual variability in dose requirements needs consideration. In this study, prolonged intervals were assessed in relation to varying dose requirements. METHODS: The study included 153 hemodialysis (HD) patients on stable SC epoetin alfa. Based on dose requirements, the patients received either 4,000 U (group I, n=51) or 10,000 U (group II, n=102) as whole 1 mL vials at prolonged intervals. The study comprised three 8-week periods: an initial period maintaining the basal regimens, an adjustment period where the intervals were prolonged, and a maintenance period. Alterations in hemoglobin (Hb), weekly doses and intervals in each group were compared. RESULTS: One hundred and thirty-seven patients completed the study (48 in group I and 89 in group II). In group I, the mean interval was prolonged from 5.4 +/- 1.9 to 7.8 +/- 3.1 days (p=0,01) with stable Hb and EPO doses. In group II, prolonged intervals were associated with a reduction in mean Hb below target level and a significant increase in EPO doses (p=0,002). Iron deficiency and inflammation could explain the poor response in approximately one-third of the patients. CONCLUSIONS: In HD patients, the optimal injection frequency should be individually adjusted. Prolonged intervals can be applied to patients with low-dose requirements. Observing iron status and inflammation is necessary for optimal response.

Enalapril Treatment in a Patient With Impaired Renal Function and Intolerance to Captopril.

In a 36-year-old woman with malignant hypertension and moderate renal insufficiency from nephrosclerosis normotension was not achieved by the combination of a beta-blocker, a vasodilator, and a loop-diuretic. The angiotensin-converting enzyme (ACE) inhibitor captopril was then added to the therapy. The blood pressure control was good. However, due to adverse reactions, captopril had to be withdrawn. Later on, the patient was successfully treated with enalapril, another ACE inhibitor, without the relapse of any adverse reactions.

A new principle suggested for detection of darbepoetin-alpha (NESP) doping.

Doping with darbepoetin-alpha, also termed novel erythropoiesis stimulating protein (NESP), a hypersialylated, very effective analogue of erythropoietin, is a serious threat in sport. We report here on a new principle for the detection of darbepoetin-alpha in serum based upon increase in immunoactivity after desialylation with neuraminidase. The method is evaluated on sera from patients taken 2-14 days after last injection of darbepoetin-alpha. Thirty-two venous blood samples and 3 capillary samples taken from finger tips were obtained from 13 patients with end stage renal disease treated with intravenous or subcutaneous injections of Aranesp, 0.45 to 2.60 microg*kg(-1). Blood samples from 37 individuals with endogenous erythropoietin were used as controls. The sera were diluted 1:2 with acetate buffer pH 5.6 with or without neuraminidase and incubated at 37 degrees C for 1 or 24 h before immunoassay. The erythropoietin immunoactivity in serum volumes of 12.5-50 microL was measured with ELISA-kits from R&D Systems Inc and medac GmbH. The relative increase in immunoactivity after desialylation was in all cases higher for the darbepoetin-alpha samples than for any of the control samples assayed in parallel, varying incubation time with the enzyme, serum volumes and batches of both ELISA-kits. The mean relative increase in immunoactivity of endogenous erythropoietin after neuraminidase was 42% with the medac-kit and 117% with R&D-kit while the corresponding figures for darbepoetin-alpha were 282% and 231% with 1 h and 299% and 256% with 24 h enzyme incubation, respectively. Endogenous and recombinant human erythropoietin showed similar relative increase after desialylation. The method to detect darbepoetin-alpha in serum is simple to perform, robust, sensitive and requires a small amount of blood. The drug was detected in all patient sera taken 2-14 days after last injection. We suggest that the method should be evaluated for the detection of darbepoetin-alpha doping in sport.

Iron isomaltoside 1000: a new intravenous iron for treating iron deficiency in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) often suffer from iron deficiency anemia necessitating treatment with intravenous iron. This study was designed to assess the safety of iron isomaltoside 1000 (Monofer) in CKD patients. The secondary objective was to assess its effect on iron deficiency anemia. METHODS: This open-label, noncomparative, multicenter trial assigned 182 patients with CKD (n=161 in dialysis and n=21 in predialysis) to iron isomaltoside 1000 either as 4 intravenous bolus injections of 100-200 mg iron per dose or as a fast high-dose infusion at baseline. Patients were generally undergoing erythropoiesis-stimulating agent (ESA) treatment (82%), and the dosage was to be kept constant during the trial. They were either switched from an existing parenteral maintenance therapy (n=144) or were not currently being treated with parenteral iron (n=38). Frequency of adverse events (AEs) and changes in markers of iron deficiency anemia were measured during 8 weeks from baseline. RESULTS: Nineteen treatment-related AEs occurred in 13 patients (7.1%) and after 584 treatments (3.3%). No anaphylactic or delayed allergic reactions were observed. There were no clinically significant changes in routine clinical laboratory tests or vital signs. Hemoglobin increased from 99.2 g/L (SD=9.0) at baseline to 111.2 g/L (SD=14.7) at week 8 in patients not currently treated with parenteral iron (p<0.001) and increased slightly or stabilized in patients in maintenance therapy. S-Ferritin, s-iron and transferrin saturation increased significantly at all visits. CONCLUSIONS: Iron isomaltoside 1000 was clinically well tolerated, safe and effective. This new intravenous iron may offer a further valuable choice in treating the anemia of CKD.

Dialysate saving by automated control of flow rates: comparison between individualized online hemodiafiltration and standard hemodialysis.

Cost reduction and quality improvement seem to be conflicting issues. However, online hemodiafiltration (oHDF) with new automatic functions offers a cost-efficient therapy compared to hemodialysis (HD). Seven dialysis centers conducted a randomized clinical trial with cross-over design: high-flux HD vs. postdilutional oHDF with functions coupling both dialysate and substitution flow rates to blood flow rates. During the 6 weeks of the study, all treatment parameters remained unchanged for HD and oHDF, apart from dialysate and substitution flow rate. Treatment data were recorded during each treatment, and predialytic and postdialytic concentrations of urea were recorded at the end of each study phase. The analysis involved 956 treatments of 54 patients. The mean dialysate consumption was 123.2 ± 6.4 l for HD and 113.4 ± 14.9 l for oHDF (p < 0.0001), the mean dialysis dose was 1.42 ± 0.23 for HD and 1.47 ± 0.26 for oHDF (p < 0.0001); oHDF resulted in a lower dialysate consumption (8.0% less) and a slightly increased dialysis dose (Kt/V 3.5% higher) compared to HD. oHDF with the investigated automatic functions offers substantial savings in dialysate consumption without decreasing dialysis dose.