Plasmatic osteopontin and vascular access dysfunction in hemodialysis patients: a cross-sectional, case-control study (The OSMOSIS Study).

BACKGROUND AND AIMS: Despite close follow-up of patients with native arteriovenous fistulas (AVFs), up to 10% experience thrombosis each year. The OSMOSIS Study (Osteopontin as a Marker of Stenosis) tested the hypothesis that the systemic osteopontin level, a pro-inflammatory mediator related to vascular remodelling and intimal hyperplasia, increases in AVF stenosis, and may be used in clinical surveillance. METHODS: Our cross-sectional study compared the level of plasmatic osteopontin (pOPN) between patients with a well-functioning AVF (control group) and patients who required revision of their AVF due to stenosis (stenosis group). Blood samples were collected before dialysis (control group) or before intervention (stenosis group) from the AVF arm, and from the opposite arm as a within-subject control. pOPN level was measured by enzyme-linked immunosorbent assay. RESULTS: A total of 76 patients were included in the study. Baseline characteristics were similar between the groups (mean age, 70 years; men, 63%; AVF duration, 39 months), apart from prevalence of type 2 diabetes (T2D) (control group, 33%; stenosis group, 57%; p = 0.04). pOPN levels were similar between the AVF arm and the contralateral arm (551 ± 42 ng/mL vs. 521 ± 41 ng/mL, respectively, p = 0.11, paired t-test). Patients in the stenosis group displayed a higher pOPN level than patients in the control group (650.2 ± 59.8 ng/mL vs. 460.5 ± 61.2, respectively, p = 0.03; two-way ANOVA). T2D was not identified as an associated factor in a multivariate analysis (p = 0.50). CONCLUSIONS: The level of pOPN in hemodialysis patients was associated with the presence of AVF stenosis requiring intervention. Thus, its potential as a diagnostic biomarker should be assessed in a vascular access surveillance program.

Alkaline Phosphatases Account for Low Plasma Levels of Inorganic Pyrophosphate in Chronic Kidney Disease.

INTRODUCTION: Patients on dialysis and kidney transplant recipients (KTR) present the syndrome of mineral and bone disorders (MBD), which share common traits with monogenic calcifying diseases related to disturbances of the purinergic system. Low plasma levels of inorganic pyrophosphate (PPi) and ectopic vascular calcifications belong to these two conditions. This suggests that the purinergic system may be altered in chronic kidney disease with MBD. Therefore, we perform a transversal pilot study in order to compare the determinants of PPi homeostasis and the plasma levels of PPi in patients on dialysis, in KTR and in healthy people. PATIENTS AND METHODS: We included 10 controls, 10 patients on maintenance dialysis, 10 early KTR 3 ± 1 months after transplantation and nine late KTR 24 ± 3 months after transplantation. We measured aortic calcifications, plasma and urine levels of PPi, the renal fractional excretion of PPi (FePPi), nucleoside triphosphate hydrolase (NPP) and ALP activities in plasma. Correlations and comparisons were assessed with non-parametric tests. RESULTS: Low PPi was found in patients on dialysis [1.11 (0.88-1.35), p = 0.004], in early KTR [0.91 (0.66-0.98), p = 0.0003] and in late KTR [1.16 (1.07-1.45), p = 0.02] compared to controls [1.66 (1.31-1.72) µmol/L]. Arterial calcifications were higher in patients on dialysis than in controls [9 (1-75) vs. 399 (25-526) calcium score/cm2, p < 0.05]. ALP activity was augmented in patients on dialysis [113 (74-160), p = 0.01] and in early KTR [120 (84-142), p = 0.002] compared to controls [64 (56-70) UI/L]. The activity of NPP and FePPi were not different between groups. ALP activity was negatively correlated with PPi (r = -0.49, p = 0.001). DISCUSSION: Patients on dialysis and KTR have low plasma levels of PPi, which are partly related to high ALP activity, but neither to low NPP activity, nor to increased renal excretion of PPi. Further work is necessary to explore comprehensively the purinergic system in chronic kidney disease.

Vitamin E-Coated and Heparin-Coated Dialyzer Membranes for Heparin-Free Hemodialysis: A Multicenter, Randomized, Crossover Trial.

BACKGROUND: Hemodialysis requires effective anticoagulation to avoid blood circuit clotting. In patients at high risk for bleeding, several alternative methods have been developed. STUDY DESIGN: Multicenter, prospective, randomized, crossover study evaluating the noninferiority of vitamin E-coated compared with heparin-coated dialyzers in a 4-hour heparin-free hemodialysis strategy. SETTINGS & PARTICIPANTS: 32 adult long-term hemodialysis patients from 2 French hemodialysis units with well-functioning fistulas or double-lumen catheters. INTERVENTION: Patients were randomly allocated to a first period using either vitamin E- or heparin-coated dialyzers. After a washout period of 2 hemodialysis sessions, each patient was switched to the alternative dialyzer for a second period. Each study period started with 2 hemodialysis sessions with reduced heparin dose (50% and 25% of usual heparin dose, respectively, for sessions 1 and 2) followed by 2 heparin-free sessions. OUTCOMES: The primary end point was the percentage of successful study periods, defined as no circuit-clotting event leading to premature interruption of any of the 4 dialysis sessions. Secondary end points included total number and cumulative duration of hemodialysis sessions without clotting, number of saline solution flushes, dialysis circuit bubble trap status and dialyzer membrane status by visual inspection, and dialysis adequacy. RESULTS: The percentage of success with vitamin E-coated dialyzers (25/32 study periods [78%]) was not inferior to that with heparin-coated dialyzers (26/32 study periods [81%]). Visual inspection showed equal numbers of clean dialysis circuit bubble traps (vitamin E-coated, 34/121; heparin-coated, 32/120), whereas clean fiber bundles were more frequently noted with the vitamin E-coated compared with heparin-coated dialyzers (25/121 vs 2/120; P=0.002). LIMITATIONS: Results may not extrapolate to critically ill patients. Differences in dialyzer transparency may account for visual inspection scores. CONCLUSIONS: The success rate of 4-hour heparin-free hemodialysis sessions is lower than that previously claimed in uncontrolled studies. Vitamin E-coated and heparin-coated dialyzers exposed patients to similar and unacceptable high failure rates. Further studies are required to improve heparin-free hemodialysis.

Patients' preferences regarding choice of end-stage renal disease treatment options.

BACKGROUND: Dialysis registries have reported a low take-up of home treatment. The aim of our study was to report patients' preferred treatment options for end-stage renal disease (ESRD) after information delivery, patients' characteristics by treatment preference, and the reasons for differences between treatment preference and the treatment delivered. METHODS: A prospective cohort study on patients seen in our nephrology department between January 2009 and June 2011 included all patients with chronic kidney disease (GFR <20 ml/min/1.73 m(2)) and incident dialysis patients who received an information program about ESRD treatment options. RESULTS: 228 patients received information delivery and either expressed a preference for a given renal replacement therapy (peritoneal dialysis, PD: 42%; hemodialysis, HD: 33%), remained undecided (20%) or expressed reluctance to undergo renal replacement therapy (5%). Multivariate analysis revealed that compared to HD preference, patients preferring PD were older (OR 1.02, 95% CI 1.0-1.04), had a lower BMI (OR 0.9, 95% CI 0.87-0.98) and were more likely to have been informed before rather than after starting dialysis (OR 3.4, 95% CI 1.5-7.4); home treatment was the main reason given for preferring PD. Undecided patients were mainly women and the majority were eventually treated by HD. Reluctant patients were the oldest (OR 1.12, 95% CI 1.02-1.22) and were rarely treated by dialysis. Only 24% of patients informed before and 8% of patients informed after starting dialysis were ultimately treated with PD. Reasons for a mismatch between dialysis modality preference and treatment delivered were equally distributed between medical and nonmedical. CONCLUSION: Patients should be systematically informed before starting dialysis, patients' preferences should be taken into account before organizing dialysis and all treatment modalities should be available in all centers.