Screening for hemodialysis graft stenosis and short-term thrombosis risk: A comparison of the available tools.

INTRODUCTION: Guidelines recommend hemodialysis graft screening to identify and repair significant (>50%) stenosis at high risk of thrombosis, but there is insufficient evidence to prefer one or other screening tool due to the lack of studies comparing all available options. METHODS: Seeking an optimal screening approach, we compared the performance of all currently used tools (duplex ultrasound to detect significant stenosis (StD) and measure access blood flow (QaD), ultrasound dilution access blood flow (QaU), static venous intra-access pressure ratio (VAPR), dynamic arterial and venous pressures measurement, and monitoring) for diagnosing significant angiography-proven stenosis (StA) and predicting incipient thrombosis (occurring within 4 months) in 62 grafts. All thrombotic and symptomatic acute hypotension episodes were recorded during follow-up. RESULTS: VAPR > 0.70 and QaU < 1600 mL/min were the best indicators to angiography for those aiming to identify the majority of StA (91% sensitivity) and QaU < 1000 mL/min or StD for those aiming to avoid unnecessary angiograms (95%-93% positive predictive value). At Cox's analysis, the only significant thrombosis predictors were acute hypotension episodes (relative risk = 4.4 (95% confidence interval = 2.2-8.8), p < 0.0001) and QaU or QaD (14% (95% confidence interval = 8-21) or 16% (95% confidence interval = 6-25) increased risk per 100 mL/min drop in Qa, p < 0.003). Thrombosis risk (adjusted for acute hypotension) became significantly higher at QaU = 1000-700 mL/min (relative risk = 3.6 (95% confidence interval = 1.6-8.2), p < 0.001) and QaD = 1300-1000 mL/min (relative risk = 3.1 (95% confidence interval = 1.1-12.8), p = 0.031). The proportion of thromboses attributable to acute hypotension was 40% (95% confidence interval = 24-57). CONCLUSIONS: Our comparative study showed that an effective screening for graft stenosis and short-term thrombosis risk can rely on Qa surveillance alone, and suggested that avoiding acute hypotension and correcting stenosis at QaU < 1000 mL/min or QaD < 1300 mL/min can contain thrombosis risk.

Pro: Vascular access surveillance in mature fistulas: is it worthwhile?

Guidelines recommend regular screening of mature arteriovenous fistulas (AVFs) for preemptive repair of significant stenosis (≥50% lumen reduction) at high risk of thrombosis, identifiable from clinical signs of access dysfunction (monitoring) or by measuring access blood flow (Qa surveillance), which also enables stenosis detection in functional accesses. To compare the value of Qa surveillance versus monitoring, a meta-analysis was performed on the randomized controlled trials (RCTs) comparing the two screening strategies. It emerged that correcting stenosis identified by Qa surveillance significantly halved the risk of thrombosis [relative risk (RR) = 0.51, 95% confidence interval (CI) 0.35-0.73] and access loss (RR = 0.47, 95% CI 0.28-0.80) in comparison with intervention prompted by clinical signs of access dysfunction. One small RCT aiming to identify an optimal Qa threshold showed that stenosis repair at Qa >500 mL/min produced a significant 3-fold reduction in the risk of thrombosis (RR = 0.37, 95% CI 0.12-0.97) and access loss (RR = 0.36, 95% CI 0.09-0.99) in comparison with intervening when Qa dropped to <400 mL/min as per guidelines. To test the real-world benefits of Qa surveillance, the expected RCT-based thrombosis and access loss rates with Qa surveillance were compared with the rates with monitoring reported in observational studies: the expected thrombosis and access loss rates with surveillance were only lower than with monitoring when a Qa >500 mL/min was considered (2.4, 95% CI 1.0-4.6 and 2.2, 95% CI 0.7-5.0 versus 9.4, 95% CI 7.4-11.3 and 10.3, 95% CI 7.7-13.4 events per 100 AVFs-year, P ≤ 0.024), suggesting that in clinical practice adopting Qa surveillance may only be worthwhile at centres with high thrombosis and access loss rates associated with monitoring, and adopting Qa thresholds >500 mL/min for elective stenosis repair.

A single dialysis session of hemodiafiltration with sorbent-regenerated endogenous ultrafiltrate reinfusion (HFR) removes hepcidin more efficiently than bicarbonate hemodialysis: a new approach to containing hepcidin burden in dialysis patients?

BACKGROUND: Most hemodialysis patients have high Hepcidin-25 levels, which may be involved in the pathogenesis of several uremic complications related to an altered iron biology. The hemodialysis procedure itself can influence Hepcidin-25 levels by removing Hepcidin-25 and maybe stimulating its production due to a pro-inflammatory effect. METHODS: To assess the relationship between dialysis-related inflammation and intradialysis changes in Hepcidin-25, we performed a crossover trial in 28 hemodialysis patients to compare the effects on serum levels of Hepcidin-25 and inflammatory markers activated during dialysis [Tumor Necrosis Factor-α (TNF-α), Interleukin-6, C-reactive protein (CRP), Pentraxin-3] of a single dialysis session using a technique capable of reducing inflammation, HFR (Hemo Filtrate Reinfusion: a hemodiafiltration system combining convection, diffusion and adsorption) or bicarbonate-dialysis using either the same low-flux membrane as in the diffusion stage of HFR (LFBD) or a high-flux membrane (HFBD). RESULTS: HFR achieved a greater reduction in Hepcidin-25 levels than both LFBD [-72% (95% CI: -11 to -133), p = 0.022] and HFBD [-137% (95% CI: -2 to -272), p = 0.047], conceivably due to both a greater removal (because of its convective/adsorptive component) and a lower inflammation-related Hepcidin-25 production. HFR also led to a greater decrease in TNF-α than LFBD [-277% (95% CI: -59 to -494), p = 0.014], while the two methods induced similar changes in Interleukin-6, CRP and Pentraxin-3 levels. CONCLUSIONS: Our findings suggest that a single bicarbonate-dialysis session can upregulate Hepcidin-25 synthesis and that HFR can fully overcome this effect, enabling a greater Hepcidin-25 removal during dialysis. Adequately-designed studies are needed, however, to establish whether the beneficial effect of HFR emerging from our study could reduce Hepcidin-25 (and TNF-α) burden and improve clinically-relevant outcomes. TRIAL REGISTRATION: ISRCTN15957905.

Clinical access assessment.

BACKGROUND: Vascular access guidelines recommend routine screening for the timely detection of stenosis using noninvasive methods, including clinical assessment (monitoring) and device-based surveillance relying on access blood flow (Qa) and static intra-access pressure (sVPR, static venous pressure ratio) measurements and duplex ultrasound (DU). METHODS: We reviewed the literature to see how monitoring compares with surveillance in terms of compliance with the World Health Organization's criteria for screening tests. RESULTS: The fundamental element of monitoring, physical examination (PE), has a fair-to-good performance in detecting stenosis in both fistulas and grafts, similar to the Qa criteria recommended in the guidelines. In fistulas, the "or" combination of a positive PE with a Qa <900 mL/min or sVPR >0.5 is more sensitive in detecting stenosis (in up to 98% of cases), making it as good as DU. In grafts, PE performed significantly less well in diagnosing stenosis than sVPR or DU.In randomized controlled trials on fistulas, Qa surveillance enables a significant halving of the risk of thrombosis and access loss by comparison with monitoring alone when Qa criteria highly sensitive to stenosis are considered. In grafts, neither Qa nor DU nor sVPR is able to reduce thrombosis or access loss rates by comparison with monitoring alone. CONCLUSIONS: Our analysis indicates that regular monitoring should be the backbone of any vascular access stenosis screening program (possibly associated with Qa and sVPR surveillance for fistulas), and PE should be part of every teaching program for caregivers involved in hemodialysis.

The rise and fall of access blood flow surveillance in arteriovenous fistulas.

Vascular access blood flow (Qa) surveillance has been described as a typical false paradigm, an example of how new tests are sometimes adopted even without good-quality evidence of their benefits. This may be true for grafts, but not necessarily for arteriovenous fistulas. We reviewed the literature on Qa surveillance in fistulas to see whether it complies with the World Health Organization's criteria for screening tests. Measuring Qa has a fairly good reproducibility. Qa shows an excellent-to-good accuracy for stenosis being the only bedside screening test that achieves a very high sensitivity while retaining a fair-to-good positive predictive value for Qa thresholds of 600 ml/minute or higher associated with a >25% drop in Qa, or findings suggesting stenosis on physical examination. The accuracy of Qa in predicting thrombosis is hard to establish because of the heterogeneity of published studies, though a Qa of 300 ml/minute seems the most reliable cutoff. Qa surveillance affords a significant 2- to 3-fold reduction in the risk of thrombosis by comparison with clinical monitoring alone when Qa criteria highly sensitive to stenosis are considered, regardless of the study design (randomized controlled trials, cohort studies with concurrent or historic controls). Using highly sensitive Qa screening criteria also halves the risk of access loss, although this effect is not statistically significant. Our analysis strongly suggests that Qa surveillance is an effective method for screening mature fistulas, though further, appropriately designed studies are needed to fully elucidate its benefits and cost effectiveness.

Should current criteria for detecting and repairing arteriovenous fistula stenosis be reconsidered? Interim analysis of a randomized controlled trial.

BACKGROUND: The vascular access guidelines recommend that arteriovenous fistulas (AVFs) with access dysfunction and an access blood flow (Qa) <300-500 mL/min be referred for stenosis imaging and treatment. Significant (>50%) stenosis, however, may be detected in a well-functioning AVF with a Qa > 500 mL/min, too, but whether it is worth correcting or not remains to be seen. METHODS: In October 2006, we began an open randomized controlled trial enrolling patients with an AVF with subclinical stenosis and Qa > 500 mL/min, to see how elective stenosis repair [treatment group (TX)] influenced access failure (thrombosis or impending thrombosis requiring access revision), or loss and the related cost compared with stenosis correction according to the guidelines, i.e. after the onset of access dysfunction or a Qa < 400 mL/min [control group (C)]. An interim analysis was performed in July 2012, by which time the trial had enrolled 58 patients (30 C and 28 TX). RESULTS: TX led to a relative risk of 0.47 [95% confidence interval (CI): 0.17-1.15] for access failure (P = 0.090), 0.37 [95% CI: 0.12-0.97] for thrombosis (P = 0.033) and 0.36 [95% CI: 0.09-0.99] for access loss (P = 0.041). In the setting of our study (in which all surgery was performed as in patient procedure) no significant differences in costs emerged between the two strategies. The mean incremental cost-effectiveness ratio for TX was €282 or €321 to avoid one episode of thrombosis or access loss, respectively. CONCLUSIONS: Our interim analysis showed that elective repair of subclinical stenosis in AVFs with Qa > 500 mL/min cost-effectively reduces the risk of thrombosis and access loss in comparison with the approach of the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, raising the question of whether the currently recommended criteria for assessing and treating stenosis should be reconsidered.

Incidence of renal replacement therapy in Veneto for 2008, 2009 and 2010.

This section of the report of the Veneto Dialysis and Transplantation Registry (VDTR) provides data on the incidence of patients receiving renal replacement therapy (RRT) in the region from 2008 to 2010. Its purpose is to provide health authorities with the information they need to plan the delivery of RRT in Veneto. Data were obtained from the VDTR, defining incident patients according to the recommendations of the Italian Dialysis and Transplantation Registry. The incidence rate was calculated per million population (pmp). Variability by province and treatment center was studied by applying multilevel modeling methods. An age-period-cohort model was used to forecast the incidence rate of RRT over the years to come. The incidence of patients on RRT was 114.23 pmp in 2008, 120.15 pmp in 2009 and 107.08 pmp in 2010. The patients' median age at the time of starting RRT was 70.5 in 2008, 68.7 in 2009 and 69.5 in 2010. During these 3 years, 66.3% of patients were male, and 33.7% were female. Incidence rates were not uniformly distributed between the provinces in the region, but were significantly higher in 2. The incidence rate of patients needing RRT seems likely to remain stable in the future, until 2015 at least. Renal vascular disease was the primary cause of end-stage renal disease (ESRD), followed closely by diabetes, while the proportion due to primary glomerulonephritis has gradually decreased. Initial dialysis modality was hemodialysis (HD) for 78% of patients, while about 20% started RRT on peritoneal dialysis (PD), and a negligible proportion had a preemptive kidney transplantation. About 35% patients began dialysis with a temporary vascular catheter; this percentage remained fairly constant until 2010. The incidence of RRT in Veneto is one of the lowest in Italy and remained substantially stable over the period 1998-2010, despite the population of patients with ESRD becoming older and more severely ill. This finding could mean a heavier burden on the welfare system in the future.

Prevalence of renal replacement therapy in Veneto for 2008, 2009 and 2010.

The aim of this section is to provide descriptive data for end-stage renal disease (ESRD) in the Veneto Region (Italy). Data were obtained from the Veneto Dialysis and Transplantation Registry (VDTR). Patients were considered to be prevalent renal replacement therapy (RRT) patients if alive on 31 December of each year examined. Prevalence is expressed per million population (pmp). The trend for prevalence of each treatment in the period examined was estimated by random effects longitudinal logistic regression. Prevalence of RRT in Veneto in the years 2008, 2009 and 2010 was 888, 923 and 950 pmp, respectively. The prevalence of RRT patients by treatment modality showed a slight increase for hemodialysis, notable stability for peritoneal dialysis and a more pronounced increase for transplantation. Every year, about 10% of peritoneal dialysis patients shifted to hemodialysis, and 12% received a transplant. The transition probability from hemodialysis to peritoneal dialysis was negligible, and less than 5% of hemodialysis patients received a transplant. The probability of returning to hemodialysis after having received a transplant was less than 2% a year. Bicarbonate hemodialysis slowly increased from 1998 to 2010, both in percentage and in prevalence per million population; conversely, hemodiafiltration (HDF) showed a mild but constant decrease. Automated peritoneal dialysis (APD), which was quantitatively almost negligible in 1998, reached the same level as continuous ambulatory peritoneal dialysis (CAPD) in 2010. The prevalence of patients undergoing living donor transplants almost doubled in the period 1998-2010. The increase of prevalence over time was not proportional for the 3 modalities of RRT: hemodialysis prevalence grew slowly, peritoneal dialysis prevalence remained stable, and renal transplant prevalence quickly increased.

Mortality in the Veneto population on renal replacement therapy.

This section reports survival rates for patients on renal replacement therapy (RRT). The data obtained from the Veneto Dialysis and Transplantation Registry (VDTR) cover the whole population in the region. Patients on RRT alive on 31 December of each year were assumed to be at risk of dying in the following year. Furthermore, time-to-event analysis was used to describe the complete history of patients from when they started RRT until they died, including transitions between the 3 main treatment modalities - hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation. The cohort of patients starting RRT from 1998 to 2010 was followed up until 31 December 2010. Survival rates from the first treatment to death were calculated according to the life table method. Relative survival and excess mortality rates were estimated according to the Ederer II method. A multistate model was used to describe changes in a patient's condition (changes of treatment, or death) over time. Among prevalent patients on RRT, the annual risk of death was 10.65% in 2008, 9.35% in 2009 and 8.86% in 2010. The overall mortality rate was 12.5 per 100 patient-years (95% confidence interval [95% CI], 12.1-13.0). The 5-year relative survival was 59% (95% CI, 57%-60%), and at 10 years relative survival was 41% (95% CI, 39%-43%); the estimated excess mortality rate was very high at the start of RRT (18 per 100 patient-years) but gradually decreased after the second year. On multivariate analysis, excess mortality was associated with age and primary renal diseases. Less than 10% of patients starting on PD shifted to HD in the first year of RRT, and a considerable proportion received a transplant, amounting to 6% in the first year, and thereafter increasing steadily: at the end of the fifth year, 34% of patients starting RRT on PD had received a transplant. HD patients behaved differently: any shift to PD was negligible, and the patients receiving a transplant amounted to only 2% in the first year and about 16% by the end of the fifth year. Cumulative mortality among HD patients was particularly high (already 18% at 1 year, and 70% at 10 years) by comparison with those on PD (8% at 1 year, 54% at 10 years). Although mortality on RRT is not particularly high in Veneto by comparison with countries other than Italy, this result is mainly due to an increasing number of patients receiving transplants, which makes them a favorably selected population. The mortality rate was high among those on HD, particularly in the first year. Our population on RRT is rather heterogeneous, and a description of the outcomes based only on the whole population may be misleading.

Acetate-free biofiltration reduces intradialytic hypotension: a European multicenter randomized controlled trial.

BACKGROUND: Intradialytic hypotension (IH) is a common complication of bicarbonate hemodialysis (BD) and contributes to the intolerance of dialysis and the high cardiovascular morbidity and mortality among dialysis patients, the risk of which can be contained by convective therapies. AIMS/METHODS: To assess whether acetate-free biofiltration (AFB), a hemodiafiltration technique found to improve intradialytic cardiovascular stability in short-term studies, can influence long-term IH rates, predialysis systolic blood pressure (SBP), cardiovascular morbidity and mortality by comparison with BD, we analyzed data from a randomized controlled trial enrolling 371 new-to-dialysis patients, 194 on BD and 177 on AFB. RESULTS: During a 3-year follow-up, AFB carried a significantly lower risk of IH (incidence rate ratio 0.60 (95% CI 0.53-0.68), p < 0.0001). SBP dropped on AFB (p = 0.01), while it did not change on BD. Cardiovascular morbidity and mortality were similar between AFB and BD. CONCLUSION: AFB carries a lower long-term IH rate and reduces SBP by comparison with BD.

In search of an optimal bedside screening program for arteriovenous fistula stenosis.

BACKGROUND AND OBJECTIVES: Guidelines recommend systematically screening for stenosis using various methods, but no studies so far have compared all of the options. A prospective blinded study was performed to compare the performance of several bedside tests performed during dialysis in diagnosing angiographically proven >50% fistula stenosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In an unselected population of 119 hemodialysis patients with mature fistulas, physical examination (PE) was conducted; dynamic and derived static venous pressure (VAPR), blood pump flow/arterial pressure (Qb/AP) ratio, recirculation (R), and access blood flow (Qa) were measured; and angiography was performed. RESULTS: Angiography identified 59 stenotic fistulas: 43 stenoses were located upstream from the venous needle (inflow stenosis), 12 were located downstream (outflow stenosis), and 4 were located at both sites. The optimal tests for identifying an inflow stenosis were Qa < 650 ml/min and the combination of a positive PE "or" Qa < 650 ml/min (accuracy 80% and 81%, respectively), the latter being preferable because it was more sensitive (85% versus 65%, respectively) for a comparable specificity (79% versus 89%, respectively). The best tests for identifying outflow stenosis were PE and VAPR, with no difference between the two (accuracy 91% and 85%, sensitivity 75% and 81%, specificity 93% and 86%, respectively), the former being preferable because it was more reproducible, easier to perform, and applicable to all fistulas. CONCLUSIONS: This study showed that fistula stenosis can be detected and located during dialysis with a moderate-to-excellent accuracy using PE and Qa measurement as screening procedures.

Bedside screening for fistula stenosis should be tailored to the site of the arteriovenous anastomosis.

BACKGROUND AND OBJECTIVES: Given different sites of stenosis and access blood flow rates (Qa), the criteria for diagnosing fistula stenosis might vary according to anastomotic site. To test this, we analyzed the database of a prospective blinded study seeking an optimal bedside screening program for fistula stenosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Several methods used during dialysis (physical examination [PE], dynamic and derived static venous pressure [VAPR], dialysis blood pump flow/arterial pressure ratio, and Qa measurement) to diagnose angiographically-proven >50% stenosis were assessed in an unselected population of hemodialysis patients with mature fistulae (43 at the wrist [distal fistulae], 76 at mid-forearm or the elbow [proximal fistulae]). RESULTS: Prevalence of inflow stenosis was uninfluenced by anastomotic site, whereas outflow stenoses were more prevalent in proximal fistulae. The best test for inflow stenosis was Qa <650 ml/min in distal fistulae and a combination of a positive PE and Qa <900 ml/m in proximal fistulae. In proximal fistulae, PE and VAPR >0.5 were both equally highly diagnostic of outflow stenosis. Tailoring choice of test to site of the anastomosis may also contain the screening-associated workload, by reducing the need to perform PE and measure VAPR, compared with a screening approach regardless of the access location. CONCLUSIONS: Our study shows that an effective bedside screening program with ≥85% accuracy for fistula stenosis can be tailored to the site of the anastomosis, Qa being the tool of choice for the wrist, and PE alone or combined with Qa and VAPR measurements for more proximally-located accesses.

Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents.

BACKGROUND: It has been suggested that hepcidin may be useful as a tool for managing iron therapy in haemodialysis (HD) patients on erythropoiesis-stimulating agents (ESA). METHODS: We used SELDI-TOF mass spectrometry assay to measure serum hepcidin-25 (Hep-25) and hepcidin-20 (Hep-20) in 56 adult HD patients on maintenance ESA to assess their ability to predict haemoglobin (Hb) response after 1 g intravenous iron (62.5 mg ferric gluconate at 16 consecutive dialysis sessions) and their relationship with markers of iron status, inflammation and erythropoietic activity. RESULTS: At multivariate analysis (in a model that also included Hb, reticulocyte, ESA dose, HFE genotype, soluble transferrin receptor [sTfR] and C-reactive protein), Hep-25 independently correlated with ferritin (ß = 0.03, P = 0.01) and the percentage of hypochromic red blood cells [%Hypo] (ß = 1.84, P = 0.01), suggesting that Hep-25 may be a useful biomarker for iron stores and bone marrow iron availability. Hep-20 correlated independently with Hep-25 (ß = 0.159, P < 0.001) and ferritin (ß = 0.006, P = 0.05), suggesting that it may be a useful additional biomarker for iron stores. On receiver operating characteristics curve analysis, neither Hep-25 nor Hep-20 significantly predicted who will increase their Hb after iron loading (AUC = 0.52 ± 0.09 and 0.54 ± 0.08, P = 0.612), and the same applied to ferritin and transferrin saturation (AUC = 0.55 ± 0.08 and 0.59 ± 0.08, P = 0.250), whereas %Hypo and reticulocyte Hb content were significant predictors (AUC = 0.84 ± 0.05 and 0.70 ± 0.08, P < 0.01). At multivariate logistic regression analysis, %Hypo was the only biomarker independently associated with iron responsiveness. CONCLUSIONS: Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status.

Evaluation of hepcidin isoforms in hemodialysis patients by a proteomic approach based on SELDI-TOF MS.

The hepatic iron regulator hormone hepcidin consists, in its mature form, of 25 amino acids, but two other isoforms, hepcidin-20 and hepcidin-22, have been reported, whose biological meaning remains poorly understood. We evaluated hepcidin isoforms in sera from 57 control and 54 chronic haemodialysis patients using a quantitative proteomic approach based on SELDI-TOF-MS. Patients had elevated serum levels of both hepcidin-25 and hepcidin-20 as compared to controls (geometric means: 7.52 versus 4.69 nM, and 4.06 versus 1.76 nM, resp., P < .05 for both). The clearance effects of a single dialysis session by different dialysis techniques and membranes were also investigated, showing an average reduction by 51.3% +/- 29.2% for hepcidin-25 and 34.2% +/- 28.4% for hepcidin-20 but only minor differences among the different dialysis modalities. Measurement of hepcidin isoforms through MS-based techniques can be a useful tool for better understanding of their biological role in hemodialysis patients and other clinical conditions.

Procalcitonin values after dialysis is closely related to type of dialysis membrane.

BACKGROUND: Infections account for considerable morbidity and mortality in patients with chronic renal failure undergoing hemodialysis (HD). Diagnosis of infection in HD patients is challenging because the most used laboratory parameters may be increased even in the absence of infection. In this setting, procalcitonin (PCT) could be useful for detection of systemic bacterial infections. METHODS: We measured high sensitivity C Reactive Protein (hsCRP) and PCT serum levels before and immediately after dialysis in 44 HD patients (22 treated with high- and 22 with low-flux membranes), without history of infections. RESULTS: Patients on HD by high-flux membranes, but not by low-flux membranes, displayed mean PCT values significantly decreased after dialysis (high-flux: 0.50 vs. 0.26 ng/mL, p=0.005; low-flux: 0.41 vs. 0.42 ng/mL, p=0.863). HsCRP levels were unchanged. HsCRP correlated with PCT values both before and after HD only in patients on HD by low-flux membranes (r=0.51 and 0.47 before and after HD respectively; p<0.05). CONCLUSIONS: Although PCT is considered a sensitive and specific diagnostic and prognostic marker of systemic bacterial infection, we suggest that specific reference ranges might be developed in patient with impaired renal function, also showing that and its clinical usefulness might be limited in patients undergoing HD with high-flux membranes.

The impact of pruritus on the quality of life of patients undergoing dialysis: a single centre cohort study.

BACKGROUND: Pruritus is common in dialysis patients, but no studies have addressed its impact on the patients' quality of life (QoL). OBJECTIVE: We sought to measure the impact of pruritus on the QoL of patients undergoing chronic hemodialysis (HHD) or peritoneal dialysis (PPD). METHODS: Pruritus intensity was measured on a 10-point visual analog scale. QoL was investigated with the 36-item Short Form of the Medical Outcomes Study questionnaire (SSF-336), the 12-item General Health Questionnaire (GHQ-12) and a dermatological questionnaire (Skindex-29). RESULTS: One hundred and thirty-nine patients on HD and 30 on PD were recruited. Pruritus was found in 88/169 patients (52.1%),with no differences between HD and PD patients. Prevalence of poor sleep in patients with pruritus was higher than in those without (559% vs. 11%; p<0.001). Both physical and mental scores of SF-36 did not correlate with the presence and the intensity of pruritus. Pruritus intensity was significantly related to poor scores in all 3 subscales of Skindex-29 (symptoms, social function and emotions). In the subscales of social function and emotions, worse scores were observed in patients undergoing HD and with minor psychiatric disorders (GHQpos). CONCLUSIONS: Pruritus had a high level of impact on all aspects of QoL and was a predictor of poor sleep. Type of dialysis and minor psychiatric disorders affect the emotional and social aspects of QoL.

Adding access blood flow surveillance to clinical monitoring reduces thrombosis rates and costs, and improves fistula patency in the short term: a controlled cohort study.

BACKGROUND: Access blood flow (Qa) measurement is the recommended method for fistula (AVF) surveillance for stenosis, but whether it may be beneficial and cost-effective is controversial. METHODS: We conducted a 5-year controlled cohort study to evaluate whether adding Qa surveillance to unsystematic clinical monitoring (combined with elective stenosis repair) reduces thrombosis and access loss rates, and costs in mature AVFs. We prospectively collected data in 159 haemodialysis patients with mature AVFs, 97 followed by unsystematic clinical monitoring (Control) and 62 by adding Qa surveillance to monitoring (Flow). Indications for imaging and stenosis repair were clinically evident access dysfunction in both groups and a Qa < 750 ml/min or dropping by >20% in Flow. RESULTS: Adding Qa surveillance prompted an increase in access imaging (HR 2.96, 95% CI 1.79-4.91, P < 0.001), stenosis detection (HR 2.55, 95% CI 1.48-4.42, P = 0.001) and elective repair (HR 2.26, 95% CI 1.16-4.43, P = 0.017), and a reduction in thromboses (HR 0.27, 95% CI 0.09-0.79, P = 0.017), central venous catheter placements (HR 0.14, 95% CI 0.03-0.42, P = 0.010) and access losses (HR 0.35, 95% CI 0.11-1.09, P = 0.071). In the Kaplan-Meier analysis, adding Qa surveillance only extended short-term cumulative patency (P = 0.037 in the Breslow test). Mean access-related costs were 1213 Euro/AVF-year in Control and 743 in Flow (P < 0.001). CONCLUSIONS: Our controlled cohort study shows that adding Qa surveillance to monitoring in mature AVFs is associated with a better detection and elective treatment of stenosis, and lower thrombosis rates and access-related costs, although the cumulative access patency was only extended in the first 3 years after fistula maturation. We are aware of the limitations of our study (non-randomization and the possible centre effect) and that further, better-designed trials are needed to arrive at a definitive answer concerning the role of Qa surveillance for fistulae.

Effect of hemodialysis on traditional and innovative cardiac markers.

The diagnostic approach to acute coronary syndrome (ACS) is challenging in patients with impaired renal function since most serum biomarkers are commonly increased in this clinical setting. Cardiac troponin T (cTnT), creatine kinase isoenzyme MB (CK MB), myoglobin, and ischemia modified albumin (IMA), were assayed in 45 patients prehemodialysis (pre-HD) and posthemodialysis (post-HD), and results were adjusted for hemoconcentration. The pre-HD values of serum IMA and cTnT were above the respective diagnostic thresholds (IMA<85 K units/L; cTnT <0.03 ng/mL) in six (13%) and 27 (60%) patients undergoing chronic HD, respectively. A significant (105.0 vs. 79.0 K units/L, P<0.0001) and variable (+38%; 95% confidence interval [CI], 12-65%) increase of serum IMA was observed post-HD, whereas the other biomarkers significantly decreased (cTnT: 0.029 vs. 0.044 ng/mL, P=0.016; CK-MB: 2.33 vs. 2.50 microg/L, P<0.0001; myoglobin: 128.1 vs. 148.7 microg/L, P<0.0001). Biomarkers of myocardial injury, especially cTnT and IMA, might be used in HD patients, provided that an appropriate diagnostic interpretation is guarantee, according to individual baseine value, metabolism, and time of sampling. Moreover, IMA might be reliably applied to stratify the long-term risk of these patients, but not for diagnosing an ACS during or immediately post-HD.

Influence of sampling time and ultrafiltration coefficient of the dialysis membrane on cardiac troponin I and T.

CONTEXT: The measurement of cardiac troponin I (TnI) and T (TnT) is essential to diagnose, guide therapy, and predict outcomes of the acute coronary syndrome. Increased levels of troponins, especially TnT, are frequently observed in patients on chronic hemodialysis (HD), reflecting ongoing and subclinical myocardial damage. OBJECTIVE: Because these markers are increasingly used for stratification of cardiac risk in these patients, their behavior during HD should be acknowledged to optimize their clinical usefulness. DESIGN: TnI and TnT were measured in 34 patients pre-HD and post-HD by either high- or low-flux membranes. The post-HD concentrations were corrected for hemoconcentration. RESULTS: Pre-HD levels above the 99th percentile reference limits of the general population of TnI (>0.06 ng/ mL) and TnT (>0.01 ng/mL) were observed in 9% (13% high-flux, 6% low-flux membranes) and 88% (94% high-flux; 83% low-flux membranes) of the patients, respectively. No significant difference was observed in mean pre-HD values between patients dialyzed by low- and high-flux membranes. The overall decrease post-HD of both troponins (-21% and -17% for TnI and TnT, respectively) only reached statistical significance in patients dialyzed by low-flux membranes (-27% and -37% for TnI and TnT, respectively). A significant correlation was observed between absolute variations of TnI and TnT pre-HD to post-HD. CONCLUSIONS: Results of our investigation attest that high-flux membranes clear both troponins more efficiently from circulation than low-flux membranes. Therefore, sampling time and ultrafiltration coefficient of the HD membrane should be regarded as potential sources of variability in the clinical interpretation of troponin measurement in HD patients.