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.

BackgroundSclerostin 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.MethodsWe 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).ResultsCAC (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.ConclusionWe 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.

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.

♦ 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.

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.