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Background/aims Prevalent dialysis patients have low scores of health-related quality of life (HRQOL) which are associated with increased risk of hospitalization and mortality. Also in CKD-5 non-dialysis patients, HRQOL scores seem to be lower as compared with the general population. This study firstly aimed to compare HRQOL between CKD-5 non-dialysis and prevalent dialysis patients in a cross-sectional analysis and to assess longitudinal changes over 1 year after the dialysis initiation. Secondly, the correlation between HRQOL and physical activity (PA) was explored. Methods Cross-sectional 44 CKD-5 non-dialysis, 29 prevalent dialysis, and 20 healthy controls were included. HRQOL was measured by Short Form-36 questionnaires to measure physical and mental domains of health expressed by the physical component summary (PCS) and mental component summary (MCS) scores. PA was measured by a SenseWear™ pro3. Longitudinally, HRQOL was assessed in 38 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before dialysis initiation until 1 year after dialysis initiation. Results PCS scores were significantly lower both in CKD-5 non-dialysis patients and in prevalent dialysis patients as compared with healthy controls (p

Background. Depression is common in individuals with chronic kidney disease (CKD). However, data on the association of albuminuria, which together with reduced estimated glomerular filtration rate (eGFR) defines CKD, with depression are scarce and conflicting. In addition, it is not clear when in the course from normal kidney function to CKD the association with depression appears. Methods. We examined the cross-sectional associations of albuminuria and eGFR with depressive symptoms and depressive episodes in 2872 and 3083 40- to 75-year-old individuals, respectively, who completed the baseline survey of an ongoing population-based cohort study conducted in the southern part of The Netherlands between November 2013. Urinary albumin excretion (UAE) was the average UAE in two 24-h urine collections and eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation based on creatinine and cystatin C. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the presence of a minor or major depressive episode was assessed with the MINI-International Neuropsychiatric Interview. Results. In total, 5.4% had a minor or major depressive episode. UAE was = 30 mg/24 h in 8.6%. In a multivariable logistic regression analysis adjusted for potential confounders, and with UAE = 10). Conclusions. Albuminuria was associated with depressive symptoms and depressive episodes, even at levels of UAE that do not fulfil the CKD criteria. Future longitudinal studies should examine the direction of this association and whether albuminuria could serve as a biomarker to identify individuals at risk of depression.

Extracellular fluid overload (FO), which is assessed using bio-impedance technologies, is an important predictor of outcome in dialysis patients and in patients with early stages of chronic kidney disease. While traditional cardiovascular abnormalities are assumed to mediate this risk, recently also, the importance of noncardiovascular factors, such as systemic inflammation and malnutrition has been shown. While both FO and inflammation are independent risk factors for mortality, recent studies have shown that their combined presence can lead to a cumulative risk profile. From a pathophysiologic viewpoint, FO and inflammation can also be mutually reinforcing. Inflammation could contribute to FO by hypoalbuminemia, capillary leakage, and a (unnoticed) decline in lean and/or fat tissue mass resulting in incorrect estimation of dry weight. Reciprocally, FO could lead to inflammation by the translocation of endotoxins through a congested bowel wall or by a proinflammatory effect of tissue sodium. The relative importance of these putative factors is, however, not clear yet and epidemiological studies have shown no clear temporal direction regarding the relationship between FO and inflammation. FO and inflammation appear to be part of (dynamic) clusters of risk factors, including malnutrition and hyponatremia. Technology-guided fluid management of the often vulnerable dialysis patient with FO and inflammation cannot yet be based on evidence from randomized controlled trials, in which these specific patients were in general not included. In the absence of those trials, treatment should be based on identifying actionable causes of inflammation and on the judicious removal of excess volume based on frequent clinical reassessment. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi= 485153. (c) 2018 S. Karger AG, Basel

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

BACKGROUNDChronic kidney disease (CKD) is associated with an increased cardiovascular disease mortality risk. It is, however, less clear at what point in the course from normal kidney function to CKD the association with cardiovascular disease appears. Studying the associations of estimated glomerular filtration rate (eGFR) and albuminuria with biomarkers of (subclinical) cardiac injury in a population without substantial CKD may clarify this issue.METHODSWe examined the cross-sectional associations of eGFR and urinary albumin excretion (UAE) with high-sensitivity cardiac troponin (hs-cTn) T, hs-cTnI, and N-terminal probrain natriuretic-peptide (NT-proBNP) in 3103 individuals from a population-based diabetes-enriched cohort study.RESULTSAfter adjustment for potential confounders, eGFR and UAE were associated with these biomarkers of cardiac injury, even at levels that do not fulfill the CKD criteria. For example, eGFR 60–CONCLUSIONSeGFR and albuminuria were already associated with biomarkers of (subclinical) cardiac injury at levels that do not fulfill the CKD criteria. Although reduced renal elimination may partly underlie the associations of eGFR, these findings support the concept that eGFR and albuminuria are, over their entire range, associated with cardiac injury.

Background Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population. Study Design Cross-sectional analyses of a prospective population-based cohort study. Setting & Participants 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study). Predictor eGFR and urinary albumin excretion (UAE). Outcomes Memory function, information processing speed, and executive function. Measurements Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease). Results UAE was cr-cys), was 88.4 ± 14.6 mL/min/1.73 m2. eGFRcr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction < 0.05) suggested that eGFRcr-cys was associated with cognitive performance in older individuals. Limitations Cross-sectional design, which limited causal inferences. Conclusions In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFRcr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are overrepresented in elderly patients. This provides specific challenges for the treatment, as the start of dialysis in vulnerable elderly patients may be associated with a rapid decline in functional performance. However, prognosis in elderly patients with ESRD is quite variable and related to the presence of comorbidity and geriatric impairments. The decision to start dialysis in elderly patients should always be based on shared decision making, which may be aided by the use of prediction models which should however not be used to withhold dialysis treatment. The treatment of ESRD in elderly patients should be based on a multidimensional treatment plan with a role for active rehabilitation. Moreover, there also appears to be a reciprocal relationship between aging and CKD, as the presence of geriatric complications is also high in younger patients with ESRD. This has led to the hypothesis of a premature aging process associated with CKD, resulting in different phenotypes such as premature vascular aging, muscle wasting, bone disease, cognitive dysfunction and frailty. Prevention and treatment of this phenotype is based on optimal treatment of CKD, associated comorbidities, and lifestyle factors by established treatments. For the future, interventions, which are developed to combat the aging process in general, might also have relevance for the treatment of patients with CKD, but their role should always be investigated in adequately powered clinical trials, as results obtained in experimental trials may not be directly translatable to the clinical situation of elderly patients. In the meantime, physical exercise is a very important intervention, by improving both physical capacity and functional performance, as well as by a direct effect on the aging process.

OBJECTIVE: Albuminuria is thought to be a biomarker of microvascular and macrovascular endothelial dysfunction. However, direct evidence for an association of microvascular endothelial dysfunction with albuminuria is limited. In addition, experimental data suggest a stronger association of microvascular endothelial dysfunction with albuminuria in individuals with than in those without diabetes.METHODS: We examined cross-sectional associations of flicker light-induced retinal arteriolar dilation (n = 2095) and heat-induced skin hyperemia (n = 1508) with 24-h albuminuria in the population-based, diabetes-enriched Maastricht Study. We used linear regression analyses to adjust for age, sex, type 2 diabetes, and cardiovascular disease risk factors. In addition, we tested for statistical interaction with type 2 diabetes.RESULTS: Median [interquartile range] albuminuria was 6.5 [3.9-11.6] mg/24 h and 8.2% had albuminuria at least 30 mg/24 h. After adjustment, albuminuria was 1.168 (95% confidence interval, 1.046-1.303) times greater in participants in the quartile with the smallest flicker light-induced retinal arteriolar dilation relative to those with the greatest dilation, and this association was stronger in participants with type 2 diabetes (Pinteraction CONCLUSION: This is the first population-based study that provides direct evidence that microvascular endothelial dysfunction is associated with albuminuria, and that this association is stronger in individuals with than in those without type 2 diabetes.

Hemodialysis (HD) is a lifesaving treatment for patients with end-stage renal disease, which is very efficient in the correction of abnormalities of the internal environment. However, this efficiency also induces significant hemodynamic, thermal, and respiratory stressors. These have parallels with the extreme physiologic demands which are normally mainly experienced by healthy subjects under adverse environmental conditions, with the difference that they must be endured by a vulnerable patient population. Hemodynamic stress induced by ultrafiltration leads to a decline in circulating blood volume, which may result in intradialytic hypotension (IDH) and changes in tissue perfusion, which may have long-term consequences for the function of vital organs such as the brain and the heart. Pronounced declines in central venous oxygen saturation have been observed during routine HD, which are related to the circulatory stress imposed upon the patient. Apart from patient-related factors, thermal stress induced by HD may lead to skin vasodilation, counteracting the normal hemodynamic response to hypovolemia, which has important pathophysiologic correlates in heat syncope. Lastly, respiratory stress is reflected by prolonged arterial hypoxemia during HD, which is both related to patient-related factors, but may also be partly because of the treatment itself, especially during the first 30-60 minutes. Whereas hypoxemia during HD is related to increased mortality, its role in the reduced tissue oxygen delivery during HD should be further defined. Treatment modifications, such as cool or temperature-controlled HD, may reduce circulatory and thermal stress, which also may translate into a reduced risk of long-term cardiac or cerebral damage. However, as circulatory stress is mainly time-dependent, prolonged, or more dialysis treatment may reduce the homeostatic burden on the patient.

Background: Intradialytic hypotension (IDH) is a common complication of haemodialysis (HD) and associated with adverse outcomes, especially when a nadir definition (systolic blood pressure Summary: Although the decline in blood volume due to removal of fluid by ultrafiltration is the prime mover, thermally induced reflex vasodilation compromises the haemodynamic response to hypovolemia. Recent studies have stressed the relevance of changes in tissue perfusion during HD, which may translate in long-term organ damage. Monitoring changes in tissue perfusion, for which emerging evidence becomes available, appears to have great promise in the fine-tuning of the dialysis procedure. Key Messages: While it is unlikely that IDH can be completely prevented, reduction in inter-dialytic weight gain, prevention of an increase in core temperature by adjusting the dialysate temperature and more frequent or prolonged dialysis treatment remain cornerstones in providing a more comfortable and safe treatment.

Background. Protein-bound uraemic toxins (PBUT), dicarbonyl stress and advanced glycation end products (AGEs) associate with cardiovascular disease in dialysis. Intensive haemodialysis (HD) may have significant clinical benefits. The aim of this study was to evaluate the acute effects of conventional and extended HD and haemodiafiltration (HDF) on reduction ratio (RR) and total solute removal (TSR) of PBUT, dicarbonyl stress compounds and AGEs. Methods. Thirteen stable conventional HD patients randomly completed a single study of 4-h HD (HD4), 4-h HDF (HDF4), 8-h HD (HD8) and 8-h HDF (HDF8) with a 2-week interval between the study sessions. RR and TSR of PBUT [indoxyl sulphate (IS), p-cresyl sulphate (PCS), p-cresyl glucuronide, 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3-acetic acid (IAA) and hippuric acid] of free and protein-bound AGEs [N-epsilon -(carboxymethyl) lysine (CML), N-epsilon-(carboxyethyl) lysine (CEL), N-delta-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine, pentosidine], as well as of dicarbonyl compounds [glyoxal, methylglyoxal, 3-deoxyglucosone], were determined. Results. Compared with HD4, HDF4 resulted in increased RR of total and/or free fractions of IAA and IS as well as increased RR of free CML and CEL. HD8 and HDF8 showed a further increase in TSR and RR of PBUT (except CMPF), as well as of dicarbonyl stress and free AGEs compared with HD4 and HDF4. Compared with HD8, HDF8 only significantly increased RR of total and free IAA and free PCS, as well as RR of free CEL. Conclusions. Dialysis time extension (HD8 and HDF8) optimized TSR and RR of PBUT, dicarbonyl stress and AGEs, whereas HDF8 was superior to HD8 for only a few compounds.

The first year following the start of haemodialysis (HD) is associated with increased mortality, especially during the first 90-120 days after the start of dialysis. Whereas the start of dialysis has important effects on the internal environment of the patient, there are relatively few studies assessing changes in phenotype and underlying mechanisms during the transition period following pre-dialysis to dialysis care, although more insight into these parameters is of importance in unravelling the causes of this increased early mortality. In this review, changes in cardiovascular, nutritional and inflammatory parameters during the first year of HD, as well as changes in physical and functional performance are discussed. Treatment-related factors that might contribute to these changes include vascular access and pre-dialysis care, dialysate prescription and the insufficient correction of the internal environment by current dialysis techniques. Patient-related factors include the ongoing loss of residual renal function and the progression of comorbid disease. Identifying phenotypic changes and targeting risk patterns might improve outcome during the transition period. Given the scarcity of data on this subject, more research is needed.

OBJECTIVES: The assessment of body composition (BC) in dialysis patients is of clinical importance given its role in the diagnosis of malnutrition and sarcopenia. Bioimpedance techniques routinely express BC as a 2-compartment (2-C) model distinguishing fat mass (FM) and fat-free mass (FFM), which may be influenced by the hydration of adipose tissue and fluid overload (OH). Recently, the BC monitor was introduced which applies a 3-compartment (3-C) model, distinguishing OH, adipose tissue mass, and lean tissue mass. The aim of this study was to compare BC between the 2-C and 3-C models and assess their relation with markers of functional performance (handgrip strength [HGS] and 4-m walking test), as well as with biochemical markers of nutrition. METHODS: Forty-seven dialysis patients (30 males and 17 females) (35 hemodialysis, 12 peritoneal dialysis) with a mean age of 64.8 +/- 16.5 years were studied. 3-C BC was assessed by BC monitor, whereas the obtained resistivity values were used to calculate FM and FFM according to the Xitron Hydra 4200 formulas, which are based on a 2-C model. RESULTS: FFM (3-C) was 0.99 kg (95% confidence interval [CI], 0.27 to 1.71, P = .008) higher than FFM (2-C). FM (3-C) was 2.43 kg (95% CI, 1.70-3.15, P < .001) lower than FM (2-C). OH was 1.4 +/- 1.8 L. OH correlated significantly with DeltaFFM (FFM 3-C - FFM 2-C) (r = 0.361; P < .05) and DeltaFM (FM 3-C - FM 2-C) (r = 0.387; P = .009). HGS correlated significantly with FFM (2-C) (r = 0.713; P < .001), FFM (3-C) (r = 0.711; P < .001), body cell mass (2-C) (r = 0.733; P < .001), and body cell mass (3-C) (r = 0.767; P < .001). Both physical activity (r = 0.456; P = .004) and HGS (r = 0.488; P = .002), but not BC, were significantly related to walking speed. CONCLUSIONS: Significant differences between 2-C and 3-C models were observed, which are partly explained by the presence of OH. OH, which was related to DeltaFFM and DeltaFM of the 2-C and 3-C models, is therefore an important parameter for the differences in estimation of BC parameters of the 2-C and 3-C models. Both FFM (3-C) and FFM (2-C) were significantly related to HGS. Bioimpedance, HGS, and the 4-m walking test may all be valuable tools in the multidimensional nutritional assessment of both hemodialysis and peritoneal dialysis patients.

Objectives: Physical inactivity in end-stage renal disease (ESRD) patients is associated with increased mortality, and might be related to abnormalities in body composition (BC) and physical performance. It is uncertain to what extent starting dialysis influences the effects of ESRD on physical activity (PA). This study aimed to compare PA and physical performance between stage 5 chronic kidney disease (CKD-5) non-dialysis and dialysis patients, and healthy controls, to assess alterations in PA during the transition from CKD-5 non-dialysis to dialysis, and to relate PA to BC. Methods: For the cross-sectional analyses 44 CKD-5 non-dialysis patients, 29 dialysis patients, and 20 healthy controls were included. PA was measured by the SenseWear™ pro3. Also, the walking speed and handgrip strength (HGS) were measured. BC was measured by the Body Composition Monitor©. Longitudinally, these parameters were assessed in 42 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before the start of dialysis and 6 months thereafter. Results: PA was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. HGS was significantly lower in dialysis patients as compared to that in healthy controls. Walking speed was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. Six months after starting dialysis, activity related energy expenditure (AEE) and walking speed significantly increased. Conclusions: PA is already lower in CKD-5 non-dialysis patients as compared to that in healthy controls and does not differ from that of dialysis patients. However, the transition phase from CKD-5 non-dialysis to dialysis is associated only with a modest improvement in AEE.

Background: Chronic kidney disease patients show changes in the endothelial surface layer (ESL). Whether hemodialysis (HD) itself or low molecular weight heparins (LMWH) induce ESL alterations is unknown. Methods: We studied the ESL in 20 HD patients with Sidestream Dark Field Imaging [measuring perfused boundary region (PBR)] and measurement of ESL constituents in plasma during HD in 2 studies. LMWH was administered at the start of HD in study A, and 120 min after the start of HD in study B. Mean platelet volume (MPV) and platelet large cell ratio (P-LCR) were also measured. Results: Syndecan-1 increased significantly 30 min after LMWH administration. sP-Selectin increased 120 min after HD start, and MPV and P-LCR decreased significantly during HD. No significant changes of PBR, sE-Selectin, sICAM-1, or sVCAM-1 were perceived. Conclusions: HD caused a significant increase in Syndecan-1 without a change in PBR. The administration of LMWH appeared to precede the rise in Syndecan-1.

Background: Frequent hemodialysis (HD) may be associated with an increased risk of vascular access complications. Studies addressing vascular access outcomes in frequent HD show conflicting results. Methods: We searched Medline for trials looking at vascular access outcomes in frequent HD. Results: Nineteen studies met the inclusion criteria; only studies with a control group were included for analysis (n = 15). The vascular access event rate was higher in intensive HD as compared to conventional HD (difference of 6.7 events per 100 patient-years, p = 0.009). Overall event rates were not significantly different between conventional and intensive HD when stratified for access type, but were notably higher in the arteriovenous grafts and catheter group as compared to the arteriovenous fistula (AVF) group. Conclusion: Intensive HD is associated with an increased risk of vascular access complications. Overall reported event rates were lower in the AVF group. Further controlled studies should investigate whether a ‘fistula first' strategy may be recommended also for intensive HD.

Item does not contain fulltext Despite advances in preventive therapy, prognosis in chronic kidney disease (CKD) is still grim. Clinical cohorts of CKD patients provide a strategic resource to identify factors that drive progression in the context of clinical care and to provide a basis for improvement of outcome. The combination with biobanking, moreover, provides a resource for fundamental and translational studies. In 2007, the Dutch government initiated and funded the String of Pearls Initiative (PSI), a strategic effort to establish infrastructure for disease-based biobanking in the University Medical Centres (UMCs) in the Netherlands, in a 4-year start-up period. CKD was among the conditions selected for biobanking, and this resulted in the establishment of the Biobank of Nephrological Diseases-NL (BIND-NL) cohort. Patients with CKD Stages 1-4 are eligible. The data architecture is designed to reflect routine care, with specific issues added for enrichment, e.g. questionnaires. Thus, the collected clinical and biochemical data are those required by prevailing guidelines for routine nephrology care, with a minimal dataset for all patients, and diagnosis-specific data for the diagnostic categories of primary and secondary glomerular disorders and adult dominant polycystic kidney disease, respectively. The dataset is supplemented by a biobank, containing serum, plasma, urine and DNA. The cohort will be longitudinally monitored, with yearly follow-up for clinical outcome. Future linking of the data to those from the national registries for renal replacement therapy is foreseen to follow the patients' lifeline throughout the different phases of renal disease and different treatment modalities. In the design of the data architecture, care was taken to ensure future exchangeability of data with other CKD cohorts by applying the data harmonization format of the Renal DataSHaPER, with a dataset based upon standardized indicator sets to facilitate collaboration with other CKD cohorts. Enrolment started in 2010, and over 2200 eligible patients have been enrolled in the different UMCs. Follow-up of enrolled patients has started, and enrolment will continue at a slower rate. The aggregation and standardization of clinical data and biosamples from large numbers of CKD patients will be a strategic resource not only for clinical and translational research, but also by its basis in routine clinical care for clinical governance and quality improvement projects.

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion >= 30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria.

Next to a high morbidity, patients with end-stage renal failure (ESRD) suffer from a complex spectrum of clinical manifestations. Both the phenotype of patients with ESRD as well as the pathophysiology of uremia show interesting parallels with the general aging process. Phenotypically, patients with ESRD have an increased susceptibility for both cardiovascular as well as infectious disease and show a reduction in functional capacity as well as muscular mass (sarcopenia), translating into a high prevalence of frailty also in younger patients. Pathophysiologically, the immune dysfunction, telomere attrition and the presence of low-grade inflammation in uremic patients also show parallels with the aging process. System models of aging, such as the homeodynamic model and reliability theory of Gavrilov may also have relevance for ESRD. The reduction in the redundancy of compensatory mechanisms and the multisystem impairment in ESRD explain the rapid loss of homeodynamic/homeostatic balance and the increased susceptibility to external stressors in these patients. System theories may also explain the relative lack of success of interventions focusing on single aspects of renal disease. The concept of accelerated aging, which also shares similarities with other organ diseases, may be of relevance both for a better understanding of the uremic process, as well as for the design of multidimensional interventions in ESRD patients, including an important role for early rehabilitation. Research into processes akin to both aging and uremia may result in novel therapeutic approaches.

BACKGROUND/OBJECTIVES: Hyponatremia is a risk factor for mortality in hemodialysis (HD) patients. It is not well known to which extent the comorbidities, malnutrition, fluid status imbalance and inflammation are related to hyponatremia and affect outcomes. SUBJECTS/METHODS: We studied 8883 patients from the European subset of the international MONitoring Dialysis Outcomes initiative. Nutritional and fluid statuses were assessed by bioimpedance spectroscopy. Fluid depletion was defined as overhydration + 1.1 l, respectively. Malnutrition was defined as a lean tissue index below the 10th percentile of age-and gender-matched healthy controls. Hyponatremia and inflammation were defined as serum sodium levels 6.0 mg/l, respectively. We used logistic regression to test for predictors of hyponatremia and Cox proportional hazards analysis to assess the association with all-cause mortality. RESULTS: Hyponatremia was predicted by the presence of malnutrition (odds ratio (OR) = 1.49 (95% confidence interval (CI) = 1.30-1.70), inflammation (OR = 1.44 (95% CI = 1.26-1.64)) and fluid overload ((> + 1.1 l to + 2.5 l) OR = 0.73 (95% CI = 0.62-0.85)) but not by fluid depletion (OR = 1.34 (95% CI = 0.92-1.96)). Malnutrition, inflammation, fluid overload, fluid depletion and hyponatremia (hazard ratio = 1.70 (95% CI = 1.46-1.99)) were independent predictors for all-cause mortality. CONCLUSIONS: In HD patients, hyponatremia is associated with malnutrition, inflammation and fluid overload. Hyponatremia maintained predictive for all-cause mortality after adjustment for malnutrition, inflammation and fluid status abnormalities. The presence of hyponatremia may assist in identifying HD patients at increased risk of death.

Oscillatory and longitudinal time patterns play a major role in human physiology. In chronic hemodialysis patients, abnormalities in both time patterns have been observed, while time patterns can also influence the response of patients to the treatment. Abnormal oscillatory patterns have been observed for ultradian rhythms (cycle time 28 h) rhythms, large seasonal differences in mortality, but also in blood pressure and interdialytic weight gain, have been observed in dialysis patients. The most important longitudinal pattern is the general reduction of life span in dialysis patients. One explanation of this phenomenon relates to the concept of accelerated aging in dialysis patients, for which there are various supportive arguments. From a phenomenological point of view, this concept translates into the high prevalence of frailty, even in young dialysis patients. A multidimensional approach appears necessary to adequately address this problem. In this review, the relevance of disturbed time patterns in dialysis patients is discussed. The changes may reflect an impairment or reduction in homeostatic/homeodynamic control in dialysis patients and also may have important prognostic and therapeutic implications.

Objective The peritoneal equilibration test (PET) using 3.86% glucose solution is preceded by a long dwell with 3.86% glucose solution. A point of concern in patients treated with automated peritoneal dialysis (APD) is the influence of the preceding short nightly dwells on the results of a standardized PET. The aim of the study was to compare net ultrafiltration, small solute transport, sodium sieving, and solute transport type between a PET preceded by a long night dwell and one preceded by short (APD) dwells. Patients and Methods 13 stable APD patients (mean age 60 ± 15 years; mean duration of peritoneal dialysis 31 ± 15 months) underwent 2 PETs: 1 preceded by short nightly dwells (PET A) and 1 preceded by a long night dwell (PET B). Results Both PETs were performed within a mean period of 8 (range 5 – 11) days. Mean total ultrafiltration of PET A was 626 ± 218 mL and PET B was 644 ± 223 mL (NS). The 4-hour results of both tests for dialysate-to-plasma (D/P) ratios of creatinine and urea, Dt/D0 ratios of glucose, and the dip in D/P sodium (sodium sieving) were similar. Classification of transport categories was identical for 10 of 13 patients. Conclusion In APD, the preceding dwell time of a 3.86% glucose PET does not influence fluid transport, solute transport, or transport type.

Background/Aims: Clinical outcome in cardiorenal syndrome type II and treated with peritoneal dialysis (PD). Methods: Retrospective analysis over a period of 10 years. Results: Twenty-four patients with mean age at start of dialysis of 67 ± 10 years had mean survival on dialysis of 1.03 ± 0.84 years (median survival 1.0 year). The number of hospitalizations for cardiovascular causes were reduced (13.7 ± 26.5 predialysis vs. 3.5 ± 8.8 days/patient/month postdialysis, p = 0.001). Patients who survived longer than the median survival time (n = 12) also had a reduced number of hospitalizations for all causes (3.7 ± 3.8 predialysis vs. 1.4 ± 2.1 days/patient/month postdialysis, p = 0.041), a lower age (62 ± 10 vs. 71 ± 8 years, p = 0.013) and fewer had diabetes (2 vs. 7 patients, p = 0.039), but left ventricular ejection fraction was not different. Conclusion: After starting PD for cardiorenal syndrome, hospitalizations for cardiovascular causes were reduced for all patients. Survival after starting PD is highly variable. Age and diabetes seem to be significant prognostic factors, but not left ventricular ejection fraction.

Whereas clinical assessment remains the mainstay of estimating dry weight in dialysis patients, subtle over- and under-hydration may remain undetected, which may result in increased short- and long-term morbidity. Various technological tools have been developed to aid the clinician in the assessment of fluid state in dialysis patients. Chest X-ray is useful in clinical management, but does not fulfill the need for rapid, noninvasive bedside testing. Vena cava echography provides a reliable estimation of right atrial pressure and was shown to be useful in the clinical management of dialysis patients, but the timing of measurement is of critical importance. New developments in bioimpedance techniques hold great promise for the routine application of this technique in the assessment and follow-up of hydration state. Cardiac biomarkers have a strong prognostic value, and may reflect overhydration indirectly because of its effect on left ventricular stress. Blood volume monitoring as a tool to assess dry weight needs further validation and standardization. Summarizing technological tools may certainly aid the clinician in the assessment of fluid state, but should always be interpreted in the clinical context of the patient. Controlled studies are needed to definitively establish the role of technological tools in detecting dry weight.

Patients with end-stage renal disease (ESRD) are placed on dialysis while they await kidney transplantation. The mortality rate among patients with ESRD is high. This review outlines the importance of preservation of residual renal function (RRF) and supports the idea of the integrated care approach to uraemia where patients start on peritoneal dialysis (PD).

Objective. This study reviews the relevant publications on the clinical effects of icodextrin in peritoneal dialysis (PD). Design. The study provides a systematic review of the literature (MEDLINE search with icodextrin as the keyword). Results. Icodextrin induces sustained transcapillary ultrafiltration during long dwell periods. It also stimulates increased removal of sodium by the peritoneal membrane, reduction of extracellular water (ECW) and total body water (TBW). Effects of icodextrin on blood pressure control and residual renal function are discrepant. Icodextrin induces a reduction in the formation of advanced glycation end-products, while the longitudinal changes in the peritoneal membrane transport are less prominent. Conclusions. Use of icodextrin in PD improves the sodium and fluid balance. Icodextrin is potentially more biocompatible, when compared with the conventional glucose solutions. The side effects are rare.

A reduction in vascular access flow poses a risk for thrombosis. We present a new technique to measure vascular access flow during dialysis based on extracorporeal temperature gradients, and their changes, on reversing the extracorporeal bloodlines without having to inject an indicator. Fistula temperatures were measured by the blood temperature monitor with normal line position and after manual switching of the bloodlines using the same extracorporeal blood flow. The access flow by our temperature gradient method (TGM) was compared to access flow derived by saline dilution with measurements in the same patients repeated in subsequent weeks. In 70 pairs of TGM and saline dilution measurements in 35 patients, the repeatability of the TGM measurements was not significantly different from that of saline dilution. There was a highly significant correlation between the two techniques with an acceptable confidence level for limits of agreement for the difference between them. It took about 9 min to complete the TGM method and about 5 min for saline dilution. Our studies show that the novel TGM method showed excellent agreement and reproducibility with the saline dilution method without the need for indicator dilution.

Background. Structural abnormalities of the common carotid artery (CCA), as assessed by ultrasound techniques, are related to cardiovascular outcome in dialysis patients. An increased intima media thickness (IMT) of the CCA may both represent a reaction to a haemodynamic burden as well as atherosclerosis. With a new ultrasound technique CCA-IMT and IMT-inhomogeneity, a novel parameter of spatial variance of the IMT, were measured and related to traditional and non-traditional risk factors. Methods. In a cross-sectional study, we included 134 dialysis patients, aged 61 � 13 years (103 on haemodialysis, 31 on peritoneal dialysis) and 41 controls, aged 60 � 8 years. Age, sex, pulse pressure, diabetes, prevalent cardiovascular disease (CVD) and height were included in the basic multiregression analysis. Ultrasound examination of the CCA was performed. We also measured serum fetuin-A, high-sensitivity C-reactive protein (hsCRP), antibodies to oxidized low density lipoproteins (anti-oxLDL antibodies), calcium, phosphate, albumin and parathyroid hormone. Results. Compared with controls, dialysis patients had a greater CCA-IMT (670mm vs 590 � 10mm; P ¼ 0.002) and a greater CCA-IMT inhomogeneity (11.0 vs 8.1%; P ¼ 0.013). Dialysis patients with CVD had a greater CCA-IMT (734mm vs 631mm; P ¼ 0.001) and IMT-inhomogeneity (13.2 vs 9.7; P ¼ 0.008) compared with patients without CVD. IMT-inhomogeneity strongly correlated with IMT (R ¼ 0.65, P < 0.0001). In multiregression analysis, serum fetuin-A and antioxLDL antibodies correlated with IMT-inhomogeneity but not with IMT. HsCRP neither correlated with IMTinhomogeneity nor with IMT. Conclusion. The present study shows that CCA-IMT and IMT-inhomogeneity were increased in dialysis patients compared with controls. Although CCA-IMT and IMT-inhomogeneity are related, the different associations between both measurements and nontraditional risk factors show that they are distinct entities.

in this way [6] . Automated peritoneal dialysis offers more freedom to the patients, but may be disadvantageous to continuous ambulatory peritoneal dialysis (CAPD) in terms of sodium removal, especially in so-called low transporters [7] . Thus, there is a great need for a more comfortable and effective renal replacement technique, also given the great shortage of donor kidneys. Ideally, such a device would function for 24 h daily, corresponding to the normal functioning of the human kidney, and would be comfortable to wear for the patient. The ultimate dream would be a bioengineered implantable kidney, but the ultimate development of such a device is not foreseeable in the near future. In this aspect, it is sobering to realize that the human kidney is constructed of more than 26 different cell types [8] , whose interaction was developed in more than 450 million years of evolution, since our ancestors left the iso-osmotic milieu of the Ordovicians seas and went on to conquer first the freshwater environment, followed by the land [9] . Of course, an implantable blood-cleansing device would not have to be a reliable replica of the normal kidney, and recently the group of Humes succeeded in achieving site-directed neovascularization of an implanted hollow-fiber hemofilter device after addition of angiogenic growth factors, resulting in formation of filtrate [10] . However, in the case of an implantable kidney, formidable problems in terms of immune tolerance, vascular access, and biocompatibility, to name only a few, still lie ahead. However, the construction of exterior devices, or developments which The commonly used dialysis techniques suffer from various drawbacks which preclude the leading of a normal life in patients with end-stage renal failure. Both hemodialysis and peritoneal dialysis are vastly inferior to renal transplantation in terms of correction of the interior milieu, due to the discontinuous nature of hemodialysis and the small efficacy in terms of solute clearance of peritoneal dialysis. This is reflected by the fact that the adjusted mortality for patients with a functioning renal transplant is 40–60% lower as compared to dialysis patients on the transplant waiting list [1] . In terms of equivalence of renal clearance, 3 times weekly hemodialysis for 4 hours corresponds roughly to a urea clearance of 13 ml/ min [2] whereas current guidelines recommend a minimum peritoneal Kt/V urea of 1.7 (roughly corresponding to a weekly peritoneal creatinine clearance of 45 ml/ min/1.73 m 2 (i.e. 8 4.5 ml/min)) for peritoneal dialysis [3] . The inefficiency of current dialysis techniques is highlighted by the importance of even small amounts of residual renal clearance in the prognosis of dialysis patients [4, 5] . Apart from these inherent drawbacks, hemodialysis and peritoneal dialysis are disadvantageous from a psychosocial point of view, because patients are either tied to a device for several hours, or have to perform several daily exchanges. Although quotidian hemodialysis results in an improvement of the quality of life and an improvement of the interior milieu, this option appears to be logistically feasible in only a selected number of dialysis centers, given the small number of patients treated Published online: September 3, 2007

The intravascular volume change in relation to the aforementioned pathophysiologic mechanisms and its possible role in the cause of dialysis-induced hypotension is discussed here

Periodical access flow measurements can predict the development and presence of vascular access flow-limiting stenosis and subsequent thrombosis. Access flow measurement has become a standard in vascular access care. Different techniques to measure access flow are available. The aim of this study was to compare an integrated access flow measurement device, based on thermodilution (Blood Temperature Monitor, BTM, Fresenius Medical Care, Bad Homburg, Germany), with the gold standard, the HD01 (Transonic Systems Inc., Ithaca, NY), whose technique is based on saline dilution.In 40 patients with end-stage renal disease, 40 vascular accesses were studied to determine the correlation between access flow measurements by both techniques. Reproducibility of access flow measurements by both techniques was assessed in 20 patients on a weekly interval.A total of 40 measurement series were performed. Average access flow measured with the saline technique and the thermodilution technique was 1053 (+/-495) ml/min and 1034 (+/-527) ml/min, respectively (p = ns) (n = 40). Correlation between access flow measurements by both techniques expressed in R was 0.79 (r = 0.89). Reproducibility of saline and thermodilution subsequent measurements with a weekly interval, expressed in relative difference (Delta xrel) was 13 (+/-11)% and 24 (+/-14)%, respectively (p < 0.01) (n = 20).BTM access flow measurements correlated well with the HD01 access flow measurements. However, the better reproducibility of HD01 and shorter measurement time compared with BTM access flow measurements should be considered when implementing access flow measurement to prevent vascular access failure.

Background. Peritoneal dialysis (PD) may be a useful technique in the treatment of patients with congestive heart failure, both with and without primary end-stage renal disease (ESRD). Methods. In the treatment of patients with ESRD and congestive heart failure (CHF), PD has theoretical advantages compared with haemodialysis (HD), such as the absence of an arteriovenous fistula and the more gradual fluid removal. In cohort studies, the incidence of heart failure was less as compared with HD, however, randomized studies on this aspect are lacking. Results. As an acute rescue treatment of patients with treatment refractory heart failure, functional improvement has been observed with the use of PD. However, fluid removal is less predictable compared with continuous haemofiltration therapies. Conclusions. As a long-term option for patients with treatment refractory CHF without ESRD, various case series showed improved functional performance and a reduction in hospitalization with the use of PD. However, also with the use of PD, median survival is still limited in these patients. Randomized studies are needed to establish the potential role of PD for this indication.

Background. An increase in aortic stiffness, as reflected by an increase in pulse wave velocity (PWV) or aortic augmentation index (AI) is an important predictor of cardiovascular mortality in dialysis patients. Dysregulation of calcification inhibitors, such as fetuin-A, is involved in vascular pathology in dialysis patients and fetuin-A is inversely related to mortality in dialysis patients. In this study, the relation between serum fetuin-A concentration and parameters of aortic stiffness was investigated in patients with end-stage renal disease. Methods. In a cross-sectional study we included 131 dialysis patients, aged 62±14 years (33 on peritoneal dialysis and 98 on haemodialysis), and 41 controls, aged 60±8 years. Time-averaged pre-dialysis values of serum albumin, Ca, P and intact parathyroid hormone were included in multiregression analysis, as were high-sensitivity C-reactive protein (hsCRP), fetuin-A, age, mean arterial pressure (MAP) and dialysis modality. PWV and AI were measured with the SphygmoCor device. Results. Mean fetuin-A concentration in dialysis patients (0.63±0.16 g/l) did not differ from controls (0.63±0.11 g/l). Median hsCRP levels in dialysis patients were higher compared with controls (4.0 vs 1.9 mg/l; P

already applied isolated ultrafi ltration in 1952. Alwall showed that ultrafi ltration resulted in far better fl uid removal when compared to haemodialysis with a high dialysate glucose concentration, which was employed until that time. However, Alwall did not report haemodynamic differences between isolated ultrafi ltration and ultrafi ltration combined with haemodialysis. It is tempting to read, in the commentary of Jonas Bergstrom himself, that the improved haemodynamic stability during isolated ultrafi ltration was actually discovered in 1973 by a technical fault of the dialysis module, which had been in bypass position without alarming, meaning that no dialysate had passed during the treatment. During this faulty treatment, fl uid removal was remarkably well tolerated in a patient who used to experience symptomatic hypotension during every treatment. Due to Bergstrom’s combination of clinical and scientifi c interest, this single observation was translated into a structured research program. The paper published in the EDTA proceedings and now again in this issue of Blood Purifi cation, confi rmed the initial observations in 6 hypotension-prone patients. As you also can read in the addendum to the EDTA proceedings paper, this road was further followed by Stanley Shaldon, who developed the sequential ultrafi ltration-haemodialysis concept. Exactly 30 years ago, in 1976, Bergstrom, Asaba, Furst and Oules presented their ground-breaking fi ndings on the benefi ts of isolated ultrafi ltration at the EDTA congress. To mark this anniversary, the present issue of Blood Purifi cation contains a reprint of the fi rst description of the benefi cial effects of isolated ultrafi ltration, compared to ultrafi ltration combined with haemodialysis, on haemodynamic stability during dialysis. Although a more detailed haemodynamic analysis of the effect of isolated ultrafi ltration was published by the same group in Kidney International in 1979 [1] , the fi rst description of its clinical effects, as discussed at the EDTA congress in 1976, never appeared as a Medline-listed paper. A commentary to this paper was written some years ago by Jonas Bergstrom (1929–2001), professor emeritus at the Karolinska Institute in Stockholm, but was also never published until now. Here, it is published together with the original paper as an acknowledgement of the reviving interest in the thermal effects of dialysis and to give credit to the initiators of this odyssey. Bergstrom, however, was not the fi rst to prescribe isolated ultrafi ltration. As you can see in fi gure 1 , Alwall [2] Published online: January 17, 2006

The cause of the increase in core temperature (CT) during hemodialysis (HD) is still under debate. It has been suggested that peripheral vasoconstriction as a result of hypovolemia, leading to a reduced dissipation of heat from the skin, is the main cause of this increase in CT. If so, then it would be expected that extracorporeal heat flow (Jex) needed to maintain a stable CT (isothermic; T-control = 0, no change in CT) is largely different between body temperature control HD combined with ultrafiltration (UF) and body temperature control HD without UF (isovolemic). Consequently, significant differences in DeltaCT would be expected between isovolemic HD and HD combined with UF at zero Jex (thermoneutral; E-control = 0, no supply or removal of thermal energy to and from the extracorporeal circulation). During the latter treatment, the CT is expected to increase. In this study, changes in thermal variables (CT and Jex), skin blood flow, energy expenditure, and cytokines (TNF-alpha, IL-1 receptor antagonist, and IL-6) were compared in 13 patients, each undergoing body temperature control (T-control = 0) HD without and with UF and energy-neutral (E-control = 0) HD without and with UF. CT increased equally during energy-neutral treatments, with (0.32 +/- 0.16 degrees C; P = 0.000) and without (0.27 +/- 0.29 degrees C; P = 0.006) UF. In body temperature control treatments, the relationship between Jex and UF tended to be significant (r = -0.51; P = 0.07); however, there was no significant difference in cooling requirements regardless of whether treatments were done without (-17.9 +/- 9.3W) or with UF (-17.8 +/- 13.27W). Changes in energy expenditure did not differ among the four treatment modes. There were no significant differences in pre- and postdialysis levels of cytokines within or between treatments. Although fluid removal has an effect on thermal variables, no single mechanism seems to be responsible for the increased heat accumulation during HD.

Introduction. From the beginning of the dialysis era, the most appropriate composition of the dialysate has been one of the central topics in the delivery of dialysis treatment. Methods. A discussion is employed to achieve a consensus on key points relating to the composition of the dialysate, focusing on the relationships with blood pressure behaviour. Results. Sodium balance is the cornerstone of intradialysis cardiovascular stability and good inter-dialysis blood pressure control. Hypernatric dialysis carries the risk of positive sodium balance, with the consequent possibility of the worsening sense of thirst and hypertension. Conversely, hyponatric dialysis may lead to negative sodium balance, with the possibility of intradialysis cardiovascular instability and ‘disequilibrium’ symptoms including fatigue, muscle cramps and headache. The goal is to remove with dialysis the exact amount of sodium that has accumulated in the inter-dialysis interval. The conductivity kinetic model is applicable on-line at each dialysis session and has been proved to be able to improve intra-dialytic cardiovascular stability in hypotension-prone patients. Therefore, it should be regarded as a promising tool to be implemented in everyday clinical practice. Serum potassium concentration and variations during dialysis treatment certainly play a role in the genesis of cardiac arrhythmia. Potassium profiling, with a constant gradient between plasma and dialysate, should be implemented in clinical practice to minimize the arrhythmogenic potential of dialysis. Calcium plays a role both in myocardial contractility and in peripheral vascular resistance. Therefore, an increase in dialysate calcium concentration may be useful in cardiac compromised hypotension-prone patients. Acid-buffering by means of base supplementation is one of the major roles of dialysis. Bicarbonate concentration in the dialysate should be personalized in order to reach a midweek pre-dialysis serum bicarbonate concentration of 22 mmol/l. The role of convective dialysis techniques in cardiovascular stability is still under debate. It has been demonstrated that dialysate temperature and sodium balance play a role and this should be taken into account. Whether removal of vasoactive, middlesized compounds by convection plays an independent role in improving cardiovascular stability is still uncertain. Conclusions. The prescription of dialysis fluid is moving from a pre-fixed, standard dialysate solution to individualization of electrolyte and buffer composition, not only during the dialysis session, but also within the same session (profiling) in order to provide patients with an optimal blood purification coupled with a high degree of tolerability.

Nepsilon-(carboxymethyl)lysine, Nepsilon-(carboxyethyl)lysine and vascular cell adhesion molecule-1 (VCAM-1) in relation to peritoneal glucose prescription and residual renal function; a study in peritoneal dialysis patients.van de Kerkhof J, Schalkwijk CG, Konings CJ, Cheriex EC, van der Sande FM, Scheffer PG, ter Wee PM, Leunissen KM, Kooman JP.MD Department of Internal Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands.BACKGROUND: Advanced glycation end products (AGEs) may contribute to peritoneal and cardiovascular damage in peritoneal dialysis (PD) patients, possibly in part by over-expression of vascular cell adhesion molecule-1 (VCAM-1). It has been suggested that peritoneal glucose load, oxidative stress, as well as the uraemic state itself may lead to an increased formation of AGEs. Aims of the present study were first to investigate the relation between residual glomerular filtration rate (rGFR), malondialdehyde (MDA) as a marker of lipid peroxidation, and peritoneal glucose prescription and absorption with serum levels of VCAM-1 and with the well characterized AGEs N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL), as well as with CML and CEL in peritoneal effluent. METHODS: CML and CEL were measured by tandem mass spectroscopy, MDA by HPLC, and VCAM-1 by ELISA in 37 stable PD patients (age 54 +/- 12 years; time on PD 25 +/- 18 months). CML and CEL were also measured after a 4-month interval. RESULTS: rGFR was independently related to CML both in serum (r = -0.66; P

Introduction. Cardiovascular (CV) disease is the main cause of morbidity and mortality in dialysis patients. Hypertension in patients affected by chronic renal insufficiency (CRI) has been recognized as one of the major classical CV risk factors in CRI from the very beginning of the dialysis era. However, its treatment is still unsatisfactory. Methods. A discussion is employed to achieve a consensus on key points relating to the epidemiological, pathophysiological and clinical characteristics of hypertension in renal patients, in the light of global CV risk assessment. Results. CV disease is accelerated by CRI, in particular by uraemia-specific risk factors. This is reflected by the fact that general population-based equations for calculating CV risk underestimate the real CV risk in CRI and dialysis patients. Hypertension in dialysis patients is clearly a major CV risk factor. Isolated systolic hypertension with increased pulse pressure is the most prevalent blood pressure (BP) anomaly in dialysis patients, due to stiffening of the arterial tree. BP should be assessed by clinical measurements on a routine basis, leaving 24 h monitoring for selected cases. The targets of BP control should be those recommended by the present guidelines, i.e.

Nitric oxide synthetic capacity in relation to dialysate temperature.Beerenhout CH, Noris M, Kooman JP, Porrati F, Binda E, Morigi M, Bekers O, van der Sande FM, Todeschini M, Macconi D, Leunissen KM, Remuzzi G.Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands.BACKGROUND: During hemodialysis, vascular reactivity is impaired, which can be corrected by lowering dialysate temperature. It has also been shown that nitric oxide (NO) is related to intradialytic hypotension. As NO synthesis may be temperature-dependent, this study addressed the influence of dialysate temperature on the NO synthetic capacity of plasma. METHODS: NO synthetic capacity was studied during hemodialysis with a dialysate temperature of 37.5 degrees C (dialysis-37.5 degrees C) and programmed extracorporeal blood cooling (cool dialysis; Blood Temperature Monitor; Fresenius C) in 12 stable patients. NO synthetic capacity was assessed ex vivo by [3H]L-citrulline formation from [3H]L-arginine in cultured endothelial cells after incubation with plasma samples obtained during the respective sessions. RESULTS: Core temperature decreased (-0.32 +/- 0.10 degrees C) and energy transfer rate was significantly lower (-27.5 +/- 2.8 W; p < 0.05) during cool dialysis compared to dialysis-37.5 degrees C (0.19 +/- 0.06 degrees C and -0.8 +/- 1.2 W respectively; p < 0.05). Systolic blood pressure decreased during dialysis-37.5 degrees C (-19 +/- 4 mm Hg; p < 0.05), but not during cool dialysis (-6 +/- 5 mm Hg). NO synthetic capacity increased during dialysis-37.5 degrees C (55.5 +/- 9.3 to 73.5 +/- 10.2 pmol/10(5) cells; p < 0.05), in contrast to cool dialysis (67.3 +/- 11.1 to 66.2 +/- 10.8 pmol/10(5) cells). CONCLUSION: The stimulatory effect of uremic plasma on endothelial NO synthesis was augmented during dialysis-37.5 degrees C but not during cool dialysis. Copyright 2004 S. Karger AG, Basel