Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study.

BACKGROUND: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. METHODS: We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 ± 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR). RESULTS: CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves. CONCLUSION: We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification.

Influence of chronic renal failure on acid secretion in isolated gastric mucosal cells from human biopsies.

It has been shown previously that the antisecretory response of famotidine (histamine H2-receptor antagonist) is altered in patients with renal failure. To evaluate the underlying mechanism(s) of this clinical observation we obtained biopsy specimens of fundic mucosa from two groups of patients with variable renal function (group 1 normal renal function (n = 8); group 2 renal insufficiency (n = 8), CL(CR) < 20 mL/min) [matched for age and sex]. Furthermore, we investigated the effect of intact parathyroid hormone (PTH (1-84)), urea and calcium on 14C-aminopyrine uptake as an indicator of acid secretion. Gastric mucosal cells from human biopsies were isolated by pronase and collagenase digestion. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and calcium stimulated 14C-aminopyrine uptake. PTH (1-84) suppressed basal 14C-aminopyrine accumulation, whereas addition of urea had no influence either in presence or in absence of histamine. In contrast to histamine, PTH (1-84) did not induce a significant increase in cellular cyclic AMP. In conclusion, there is no difference in the activation of 14C-aminopyrine uptake between patients with normal renal function and renal insufficiency except lower basal values in patients with renal failure. This could be caused by PTH (1-84) and urea which inhibit gastric acid secretion. Only calcium is the important agent causing an increase in the sensitivity of parietal cells in hyperparathyroidism.

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients.

Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 +/- 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 +/- 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 +/- 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = -0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

Predictors of low circulating endothelial progenitor cell numbers in haemodialysis patients.

BACKGROUND: End-stage renal disease (ESRD) patients exhibit increased cardiovascular mortality associated with cardiovascular calcifications and endothelial dysfunction. As circulating endothelial progenitor cells (EPCs) harbour vascular regenerative potential and are altered in uraemia, we examined clinical and biochemical factors influencing EPC levels as well as the relation between EPC numbers and function and uraemic cardiovascular calcifications. METHODS: Sixty-five haemodialysis patients were investigated. Cardiovascular calcifications were assessed by multi-slice spiral CT (MSCT, n = 44) with the calculation of coronary Agatston scores and indirectly by carotid-femoral pulse wave velocity (PWV, n = 61). EPCs were quantified in peripheral blood (CD34(+)/KDR(+)) and at day 7 after ex vivo cultivation (ac-LDL(+)/lectin(+)) by flow cytometry. In addition, colony-forming units (CFUs), migratory activity, adhesion and viability of isolated EPCs were analysed. RESULTS: EPC numbers were reduced (P < 0.001) compared to 27 healthy controls (-64%) or 81 patients with documented coronary artery disease and normal renal function (-58%). Coronary calcifications did not exhibit a significant association with the numbers of circulating CD34(+)/KDR(+) or isolated ac-LDL(+)/lectin(+) EPCs. No difference in EPC functions was observed between the 10 patients with the lowest Agatston scores (range 0-41) versus those with the highest scores (range 1181-3736). Multivariate analysis revealed low fetuin-A serum levels to be a positive predictor, while haematocrit and reticulocytes were negative predictors of reduced ac-LDL(+)/lectin(+) EPC numbers. CONCLUSIONS: EPC numbers and function did not correlate with the degree of coronary calcifications in haemodialysis patients. Rather they appear to be related to serum fetuin-A levels, haematocrit and reticulocytes.

Undercarboxylated matrix GLA protein levels are decreased in dialysis patients and related to parameters of calcium-phosphate metabolism and aortic augmentation index.

BACKGROUND: Vascular calcifications are related to cardiovascular mortality and morbidity in dialysis patients. Limited data exist on the role of calcification inhibitors, such as matrix-carboxyglutamic acid protein (MGP) in dialysis patients. METHODS: In 120 dialysis patients and 41 age-matched healthy controls, circulating undercarboxylated (uc) MGP levels were measured with a novel ELISA-based competitive assay. The association between ucMGP levels and determinants of bone mineral metabolism, including the calcification inhibitor fetuin-A, was studied. Moreover, the relation between ucMGP levels and arterial stiffness was investigated. RESULTS: The ucMGP level was significantly lower in dialysis patients compared to controls (173 +/- 70 vs. 424 +/- 126 nmol/l; p < 0.0001). After adjustment for age, sex and duration of dialysis an independent negative association between time-averaged phosphate levels [regression coefficient beta with 95% confidence interval = -64 (-107 to -21)] and a positive association between serum ucMGP and fetuin-A [131 (55-208)] was observed. Duration of dialysis was inversely correlated with ucMGP (r = -0.24, p = 0.007). ucMGP levels were not related to high-sensitivity C-reactive protein or time-averaged calcium levels. After adjustment for age, sex, cardiovascular disease, diabetes, height and mean arterial pressure, ucMGP level was negatively associated with the aortic augmentation index [-0.036 (-0.061 to -0.010)] but not with pulse wave velocity or pulse pressure. CONCLUSION: Significantly lower serum ucMGP levels were observed in dialysis patients compared to healthy controls. ucMGP levels were inversely associated with phosphate and positively associated with serum fetuin-A levels. Furthermore, ucMGP levels were inversely associated with the aortic augmentation index. These data suggest that low ucMGP levels may be a marker of active calcification.

Epicardial adipose tissue in long-term hemodialysis patients: its association with vascular calcification and long-term development.

BACKGROUND: Epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) in the general population. EAT is suggested to promote CAD by paracrine mechanisms and local inflammation. We evaluated whether in chronic hemodialysis (HD) patients EAT associates with CAD, how the amount of EAT develops over time, and if EAT independently predicts the mortality risk. METHODS: Post-hoc analysis of a prospective study in 59 chronic HD patients who underwent non-enhanced multi-slice computed tomography (MSCT) at baseline. Thirty-seven patients underwent another MSCT after 24 ± 5 months. We measured EAT volume (cm³) and Agatston calcification scores of coronary arteries (CAC) and aortic valves (AVC). All-cause mortality was assessed after a follow-up of 88 months (IQR 52-105). RESULTS: Baseline EAT was 128.2 ± 60.8 cm³ and significantly higher than in a control group of non-renal patients (94 ± 46 cm³; p < 0.05). Median Agatston score for CAC was 329 (IQR 23-1181) and for AVC was 0 (IQR 0-25.3) in HD patients. We observed significant positive correlations between baseline EAT and age (r = 0.386; p = 0.003), BMI (r = 0.314; p = 0.016), CAC (r = 0.278; p = 0.03), and AVC (r = 0.282; p = 0.03). In multivariate analysis, age, BMI and AVC remained as significant predictors of EAT (p < 0.01). Calcification scores significantly increased over 2 years; in contrast EAT change was not significant (+11 %, IQR -10 to 24 %; p = 0.066). The limited patient number in the present study precludes analysis of the EAT impact upon survival. CONCLUSION: EAT correlated significantly with cardiovascular calcification in long-term HD patients. Mean EAT did not significantly change over 2 years.

Arterial wall properties in patients with renal failure.

Hemodialysis (HD) patients commonly show abnormalities of the arterial system. Only a few studies have focused on arterial wall properties in patients with early stages of renal insufficiency and patients on peritoneal dialysis (PD) therapy. In this study, the distensibility coefficient (DC), a marker of arterial stiffening and intima media thickness (IMT) of the common carotid artery (CCA) and a surrogate marker of atherosclerosis, was assessed in four age-matched groups of patients: 18 HD patients, 36 PD patients, 30 patients with chronic renal failure (CRF) not yet on dialysis therapy with a creatinine clearance (CCl) between 10 and 70 mL/min, and 25 normotensive controls with normal renal function. Arterial wall properties were assessed by an automated vessel wall detection system. In patients with CRF and HD patients, but not PD patients, the DC of the CCA was significantly reduced (P < 0.05) compared with controls (CRF, 12.6 +/- 7.5 10(-3)/kPa; HD, 11.6 +/- 7.6 10(-3)/kPa; and PD, 14.7 +/- 6.2 10(-3)/kPa compared with controls, 16.7 +/- 4.6 10(-3)/kPa). In patients with CRF, a significant relationship was found between CCl and the DC (r = 0.41; P = 0.02). IMT was not different among patients with CRF (589 +/- 115 microm), HD (622 +/- 115 microm) and PD patients (585 +/- 121 microm), and controls (668 +/- 150 microm). In conclusion, compared with controls, the DC of the CCA was significantly reduced in HD patients and those with CRF, but not PD patients. In patients with CRF, the DC correlated significantly with CCl. IMT did not differ between groups of renal patients and controls.

Deficiencies of calcium-regulatory proteins in dialysis patients: a novel concept of cardiovascular calcification in uremia.

Dialysis patients suffer a manifold increase in cardiovascular mortality when compared to a nonuremic population, while this phenomenon is not sufficiently explained by an increased prevalence of traditional risk factors, such as hypercholesterolemia and hypertension. The presence of hyperphosphatemia, of an increased calcium x phosphate product, as well as the magnitude of vascular and valvular calcifications, were recently identified as specific major risk factors of cardiovascular mortality in the uremic population. Furthermore, hyperphosphatemia and an increased calcium x phosphate product could be quantitatively linked to the burden of coronary artery calcification in young dialysis patients, suggesting the correction of hyperphosphatemia as the central target for preventive therapeutic intervention. Recent studies in knockout mice, however, point to the alternative possibility that deficiencies in calcium-regulatory proteins may represent important pathomechanisms leading to extraosseous calcifications. alpha 2-Heremans Schmid glycoprotein (Ahsg/fetuin) and matrix Gla protein (MGP) are strong inhibitors of calcification in vivo. Novel evidence that deficiencies of such proteins may be involved in the pathogenesis of cardiovascular calcifications in dialysis patients will be discussed.

Determinants of arterial distensibility in patients with renal failure.

BACKGROUND: An increased stiffness of the arterial system is an adverse risk factor for the outcome in patients with renal disease. Few studies have focused on the determinants of an increased arterial stiffness in patients with renal failure. As the percentage of patients with renal failure secondary to vascular disease and/or diabetes mellitus is rapidly growing, and the underlying disease per se may also influence the arterial wall properties, it may also be of interest to study the arterial wall properties in relation to the etiology of kidney disease. METHODS: The distensibility coefficient (DC) of the common carotid artery was used as a marker of arterial stiffness. One hundred and seventeen patients were studied: 47 patients (aged 63 +/- 10 years) with renal failure secondary to vascular disease and/or diabetes mellitus and 70 patients (aged 57 +/- 13 years) with other diagnoses. The origin of the renal failure was retrieved from the patients' charts. RESULTS: Age, mean arterial pressure, and serum calcium level were each independent predictors of arterial stiffness (DC). The DC was significantly lower in the patients with vascular renal disease or diabetes mellitus [11.0 +/- 5.5 (1/MPa)] as compared with patients with renal/urological diseases [15.4 +/- 7.5 (1/MPa)]. Nevertheless, after correction for potentially confounding variables, the relation between cause of renal disease and DC lost significance in the overall group, but remained significant (p < 0.05) in the younger age groups (

Fluid status, blood pressure, and cardiovascular abnormalities in patients on peritoneal dialysis.

OBJECTIVE: Hypertension, reduced arterial distensibility, and left ventricular hypertrophy (LVH) are risk factors for mortality in hemodialysis patients. However, few studies have focused on the relation between fluid status, blood pressure (BP), and cardiovascular abnormalities in peritoneal dialysis (PD) patients. This study was designed, first, to assess, using tracer dilution techniques, fluid status in PD patients compared to a control population of stable renal transplant (RTx) patients; second, to study the relation between fluid status, BP, and arterial wall abnormalities; third, to assess the determinants of cardiac structure; and last, to compare office and ambulatory BP measurements with respect to cardiac abnormalities. DESIGN: Cross-sectional study. SETTING: Multicenter study. PATIENTS: 41 stable PD patients with a mean Kt/V urea of 2.4 +/- 0.7, and 77 stable RTx patients. INTERVENTION: Fluid status was assessed by tracer dilution techniques: extracellular volume (ECV) with bromide dilution; total body water (TBW) with deuterium oxide; and plasma volume (PV) with dextran 70. Echocardiography was performed to assess left ventricular mass (LVM), left ventricular end diastolic diameter (LVEDD), and relative wall thickness as indicators of LVH. Echography of the common carotid artery was performed to assess arterial distensibility. Both office and 24-hour ambulatory BP measurements were performed. RESULTS: Fluid status, as assessed by ECV corrected for body surface area (BSA) (ECV:BSA), was significantly different between PD and RTx patients (9.4 +/- 2.6 vs 8.6 +/- 1.2 L/m2, p < 0.05). In 36.6% of the PD patients, ECV:BSA was above the 90th percentile of the RTx patients. Fluid status corrected for BSA, assessed by TBW (TBW:BSA), ECV (ECV:BSA), or plasma volume (PV:BSA), was significantly related to diastolic BP (DBP) (r = 0.35, r = 0.37, r = 0.53; p < 0.05). Arterial distensibility of the common carotid artery was related to systolic BP (SBP) (r = -0.36, p < 0.05). ECV was significantly related to LVEDD (r = 0.41, p < 0.05) as a marker of eccentric LVH, whereas arterial distensibility was related to relative wall thickness (r = -0.53, p < 0.001) as a marker of concentric LVH. An abnormal day-night BP rhythm, which was not related to fluid status, was observed in 68.4% of patients. Ambulatory DBP and SBP but not office DBP and SBP were related to LVM (r = 0.43, r = 0.46; p < 0.01). CONCLUSIONS: A large proportion of PD patients whose treatment prescriptions are in accordance with the Dialysis Outcomes Quality Initiative guidelines were found to be overhydrated compared with a population of stable RTx patients. Fluid status was significantly related to DBP and eccentric LVH, whereas arterial distensibility of the common carotid artery was significantly related to SBP and concentric LVH. In contrast to ambulatory BP, office BP was not related to LVM.

Assessment of fluid status in peritoneal dialysis patients.

OBJECTIVES: To assess the influence of abnormalities in fluid status and body composition on agreement between multifrequency bioimpedance analysis (MF-BIA), segmental BIA (sigmaBIA), the Watson formula, and tracer dilution techniques. DESIGN: Cross-sectional. SETTING: Multicenter. PATIENTS: 40 patients (29 males, 11 females) on peritoneal dialysis (PD). MAIN OUTCOME MEASURES: Agreement between the various techniques used to assess total body water (TBW) [MF-BIA, deuterium oxide (D2O), and the Watson formula] and extracellular water (ECW) [MF-BIA, bromide dilution (NaBr), and sigmaBIA], also in relation to the relative magnitude of the body water compartments [ECW (NaBr):body weight (BW) and TBW (D2O):BW] and body composition (DEXA). Second, the relation between body water compartments with echocardiographic parameters. RESULTS: Wide limits of agreement were observed between tracer dilution techniques and MF-BIA [TBW (D2O - MF-BIA) 2.0 +/- 3.9 L; ECW (NaBr - MF-BIA) -2.8 +/- 3.9 L], which were related to the relative magnitude of the body water compartments: r = 0.70 for ECW and r = 0.40 for TBW. sigmaBIA did not improve the agreement [ECW (NaBr-sigmaBIA): 3.7 +/- 2.9 L]. Also, wide limits of agreement were observed between D2O and the Watson formula (-2.3 +/- 3.3 L). The difference between D2O and Watson was related to hydration state and to percentage of fat mass (r = 0.70 and r = -0.53, p < 0.05). Both ECW and TBW as assessed by BIA and tracer dilution were related to echocardiographic parameters. CONCLUSION: Wide limits of agreement were found between MF-BIA and sigmaBIA with dilution methods in PD patients, which were related to hydration state itself. The disagreement between the Watson formula and dilution methods was related to both hydration state and body composition.

The influence of bicarbonate/lactate-buffered PD fluids on N{ε}-(carboxyethyl)lysine and N{ε}-(carboxymethyl)lysine in peritoneal effluent.

OBJECTIVE: Accumulation of advanced glycation end products (AGEs) may be involved in the pathogenesis of peritoneal membrane dysfunction. As glycoxidation may play an important role in AGE formation, peritoneal dialysis fluids with low levels of glucose degradation products (GDPs) might result in a reduction in AGE concentration in the peritoneal effluent. The aim of this study was to compare the effects of conventional glucose-containing dialysis solutions and low GDP level fluids on the concentration of the AGEs N(ε)-(carboxymethyl)lysine (CML) and N(ε)-(carboxyethyl)lysine (CEL) in peritoneal effluent. DESIGN: Prospective randomized control study. METHODS: 23 patients were treated with either conventional glucose-containing fluid (n = 11, group A) or low level GDP fluid (n = 12, group B) during a period of 12 weeks. Before and after this period, CML and CEL were measured in peritoneal effluent. RESULTS: In groups A and B there were changes in CML concentrations [respectively 13.7 ± 17.0 and -16.0 ± 46.0 nmol/L (NS)] and CEL concentrations (respectively 20.3 ± 26.6 and -8.8 ± 18.9 nmol/L, p = 0.015). Residual renal function (RRF) in groups A and B was, respectively, 6.8 and 6.1 mL/min (NS). CML, but not CEL, in the peritoneal effluent was inversely related to RRF (r = -0.67, p < 0.05). CONCLUSION: CEL, but not CML, in the peritoneal effluent appears to be influenced by the prescription of low GDP level fluid, probably due to the highly reduced concentration of methylglyoxal, which is needed for formation of CEL. CML is primarily influenced by RRF.

Spatial inhomogeneity of common carotid artery intima-media is increased in dialysis patients.

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 (670 microm vs 590+/-10 microm; P=0.002) and a greater CCA-IMT inhomogeneity (11.0 vs 8.1%; P=0.013). Dialysis patients with CVD had a greater CCA-IMT (734 microm vs 631 microm; P=0.001) and IMT-inhomogeneity (13.2 vs 9.7; P=0.008) compared with patients without CVD. IMT-inhomogeneity strongly correlated with IMT (R=0.65, P<0.0001). In multiregression analysis, serum fetuin-A and anti-oxLDL antibodies correlated with IMT-inhomogeneity but not with IMT. HsCRP neither correlated with IMT-inhomogeneity 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 non-traditional risk factors show that they are distinct entities.

Study on the relationship of serum fetuin-A concentration with aortic stiffness in patients on dialysis.

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<0.0001). PWV but not AI was higher in dialysis patients than in controls (9.9 vs 7.9 m/s; P<0.0001). In univariate analysis in dialysis patients, fetuin-A levels were inversely related to both PWV (r = - 0.25, P = 0.007) and AI (r = - 0.26, P = 0.006), respectively. However, after correction for age, gender, MAP and diabetes mellitus, this relation lost statistical significance. CONCLUSIONS: In a dialysis population with a relatively low level of inflammatory activity, the soluble calcification inhibitor fetuin-A could not be identified as an independent predictor of aortic stiffness as measured with PWV and AI.

Energy transfer is the single most important factor for the difference in vascular response between isolated ultrafiltration and hemodialysis.

Differences in vascular reactivity between isolated ultrafiltration (i-UF) and hemodialysis (UF + HD) have been attributed to various factors, including differences in core temperature (CT) and energy transfer (ET). However, the relative importance of these thermal factors is not known. The aim of this study was to elucidate to what extent differences in ET are responsible for the divergent vascular response between i-UF and UF + HD. During four different dialysis treatments in 15 patients, four measurements were performed that consisted of 1 h of i-UF, UF + HD at a dialysate temperature (T(d)) of 37.5 degrees C (UF + HD(37.5)), UF + HD at T(d) 35.5 degrees C (UF + HD(35.5)), and UF + HD with a similar ET as during i-UF(UF + HD(ET-set)). The UF rate in all sessions was 1 L/h. CT ( degrees C) decreased significantly during i-UF and UF + HD(ET-set) (P < 0.05), increased significantly during UF + HD(37.5) (P < 0.05), and remained unchanged during UF + HD(35. 5) (NS). Forearm vascular reactivity increased significantly during i-UF, UF + HD(ET-set), and UF + HD(35.5) (P < 0.05), but not during UF + HD(37.5) (NS). Venous tone increased significantly during i-UF, UF + HD(35.5), and UF + HD(ET-set) (P < 0.05), and decreased significantly during UF + HD(37.5) (P < 0.05). When i-UF and UF + HD are matched for ET, all differences in vascular response disappear, showing that differences in ET are the single most important factor for the observed difference in vascular response between i-UF and UF + HD. In contrast to UF + HD(37.5), vascular reactivity was improved when the increase in CT was prevented during UF + HD(35.5) and appeared to increase more when CT was lowered. Preventing the increase in CT during UF + HD appears to be mandatory for optimization of hemodynamic stability during dialysis.

Fluid status in CAPD patients is related to peritoneal transport and residual renal function: evidence from a longitudinal study.

BACKGROUND: Both peritoneal transport characteristics as well as residual renal function are related to outcome in patients treated with continuous ambulatory peritoneal dialysis (CAPD). It has been suggested that part of this relationship might be explained by an effect of both parameters on the fluid state in CAPD patients or by the relationship between inflammation and peritoneal transport. METHODS: In the present study, the relationship between fluid state [extracellular water (ECW) (sodium bromide); total body water (TBW) (deuterium oxide)] with peritoneal transport characteristics (2.27% glucose dialysate/plasma creatinine [D/P (creat)] ratio), residual renal function (residual glomerular filtration rate [rGFR] by urine collection) and C-reactive protein (CRP) was assessed in 37 CAPD patients in a cross-sectional and longitudinal design, with 25 patients completing the study. RESULTS: In the cross-sectional part ECW, corrected for height (ECW:height), was inversely related to rGFR (r=-0.40, P=0.016), whereas during the longitudinal part, D/P[creat] was related to the change in ECW (r=0.40, P=0.05). Neither D/P[creat] nor rGFR were related to CRP, whereas a significant relationship was observed between ECW:height and CRP (r=0.58, P=0.0001). Patients were dichotomized according to rGFR (<2 or >2 ml/min). Despite a higher daily peritoneal glucose prescription (216.3+/-60.0 vs 156.5+/-53.0 g/24 h; P=0.004) and peritoneal ultrafiltration volume (1856+/-644 vs 658+/-781 ml/24 h, respectively; P=0.0001), the patients with a rGFR <2 ml/min showed a higher ECW:height compared with the group with rGFR >2 ml/min (12.5+/-3.8 vs 9.2+/-2.2 l/m, respectively; P=0.003). Results for TBW were comparable. CONCLUSION: Fluid state was significantly related to peritoneal transport characteristics and rGFR. The larger ECW:height in CAPD patients with a negligible rGFR existed despite a higher peritoneal ultrafiltration volume and higher peritoneal glucose prescription. These findings raise doubts as to whether fluid state in CAPD patients with a diminished rGFR can be adequately controlled on standard glucose solutions without an additional sodium and fluid restriction. The preliminary finding of a relationship between CRP and fluid state might suggest a relationship between overhydration and inflammation.

Effect of icodextrin on volume status, blood pressure and echocardiographic parameters: a randomized study.

Overhydration is a risk factor for hypertension and left ventricular hypertrophy in peritoneal dialysis patients. Recently, a high prevalence of subclinical overhydration was observed in peritoneal dialysis patients. Aim of the present open-label randomized study was to assess the effect of a icodextrin 7.5% solution on fluid status [extracellular water (ECW) bromide dilution], blood pressure regulation (24-hour ambulatory measurements) and echocardiographic parameters during a study period of 4 months, and to relate the effect to peritoneal membrane characteristics (dialysate/plasma creatinine ratio). Forty peritoneal dialysis patients (22 treated with icodextrin, 18 controls) were randomized to either treatment with icodextrin during the long dwell or standard glucose solutions. Thirty-two patients (19 treated with icodextrin, 13 controls] completed the study. The use of icodextrin resulted in a significant increase in daily ultrafiltration volume (744 +/- 767 mL vs. 1670 +/- 1038 mL; P = 0.012) and a decrease in ECW (17.5 +/- 5.2 L vs. 15.8 +/- 3.8 L; P = 0.035). Also the change in ECW between controls and patients treated with icodextrin was significant (-1.7 +/- 3.3 L vs. +0.9 +/- 2.2 L; P = 0.013). The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but significantly related to the fluid state of the patients (ECW:height) (r = -0.72; P < 0.0001). Left ventricular mass (LVM) decreased significantly in the icodextrin-treated group (241 +/- 53 grams vs. 228 +/- 42 grams; P = 0.03), but not in the control group. In this randomized open-label study, the use of icodextrin resulted in a significant reduction in ECW and LVM. The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but was related to the initial fluid state of the patient.