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.

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.

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.

Influence of haemodialysis on high-sensitivity C-reactive protein, lipoprotein(a), apolipoproteins A and B.

OBJECTIVES: There is debate on the influence of haemodialysis (HD) on lipoprotein(a). DESIGN AND METHODS: Lp(a), apo A, apo B and high-sensitivity C-reactive protein (hs-CRP) were measured in 46 patients pre- and post-HD. RESULTS: The median Lp(a) concentration significantly decreased post-HD (106 vs. 145 mg/L, p<0.001). No significant variations were observed for apo A, apo B and hs-CRP. Comparable results were observed with high- and low-flux membranes. CONCLUSION: HD is effective in lowering Lp(a).

Outcomes of surgical revision of stenosed and thrombosed forearm arteriovenous fistulae for haemodialysis.

BACKGROUND: Surgery is an established treatment for stenosed and thrombosed forearm arteriovenous fistulae (AVFs), but the literature on its outcome is limited. We report our experience of the surgical repair of stenosis in patent and thrombosed forearm AVFs and evaluate the outcome of two procedures, proximal neo-anastomosis (NEO) vs replacement of the stenosed segment with a polytetrafluoroethylene graft interposition (GI). METHODS: Sixty-four stenosed forearm AVFs underwent surgery, 32 pre-emptively and 32 post-thrombosis. End points of the study were initial success, restenosis and access loss rates. After treatment, AVFs were surveilled for restenosis by measuring access flow quarterly and performing at least one follow-up angiogram. RESULTS: Initial procedural success was 92%; 100% for patent and 84% for thrombosed AVFs. The restenosis rate was 0.189 events/AVF-year for both patent and thrombosed AVFs, while the access loss rate was 0.016 events/AVF-year in patent and 0.148 in thrombosed AVFs. Stenosis was corrected by NEO in 27 AVFs and by GI in 30. The restenosis and access loss rates were 0.151 vs 0.214 and 0.033 vs 0.019 events/AVF-year for NEO vs GI, respectively. At Cox's hazard analysis, no variable was significantly associated with restenosis, while the timing of intervention was the only significant determinant of access loss, repaired clotted accesses carrying an 8.0-fold relative risk of access loss compared with patent AVFs (P=0.048). CONCLUSION: Our study shows that surgery remains a valid option for the pre-emptive repair of stenosis and to salvage clotted forearm AVFs, offering an excellent initial success rate and low restenosis rate. It confirms that it is better to treat stenosis pre-emptively than post-thrombosis (though the restenosis rate appears to be uninfluenced by the timing of intervention) and suggests that GI compares favourably with conventional NEO.

Practice patterns in the management of arteriovenous fistula stenosis: a northern Italian survey.

BACKGROUND: Clinical practice for stenosis detection and treatment in arteriovenous fistulas (AVFs) varies widely and is largely dictated by local customs and expertise. METHODS: In May 2003, a questionnaire was sent to 32 hemodialysis (HD) facilities in north-eastern Italy, to assess the prevalence of patients with an AVF; the screening criteria for stenosis; the preferred imaging technique; the timing of the intervention and the treatment modality for stenosed and thrombosed AVFs. RESULTS: The response rate was 87%; 2895 prevalent patients were evaluated, 86% with an AVF. All facilities routinely screened for stenosis; the majority relying on clinical assessment (86%), and many on multiple surveillance methods by monitoring dialysis pressures and blood pump flow rate (75-68%), measuring access recirculation (64%), Kt/V (54%) and access blood flow rate (11%). Angiography and Doppler ultrasound were used in equal proportion for imaging. All nephrologists agreed on pre-emptive stenosis correction, 57% taking action on well functioning and 43% on failing AVFs. Forty percent of nephrologists preferred either angioplasty or surgery for pre-emptive stenosis correction, while only 18% used both. Surgery was favored over endovascular techniques (57 vs. 36%) for treating thrombosed AVFs, while only 7% of facilities used both. CONCLUSIONS: Our survey shows that, as in 2003, the vast majority of patients in north-eastern Italy were dialyzed with an AVF. Screening for stenosis was universally adopted, though most facilities relied on clinical examination and surrogate access blood flow rate markers. All nephrologists agreed to pre-emptive stenosis correction, and surgery retained a relevant role in the treatment of stenosed and thrombosed AVFs.

Endovascular versus surgical preemptive repair of forearm arteriovenous fistula juxta-anastomotic stenosis: analysis of data collected prospectively from 1999 to 2004.

Surgery is the traditional treatment for juxta-anastomotic stenoses in forearm arteriovenous fistulas (AVF), but percutaneous transluminal angioplasty (PTA) is a suitable alternative. No prospective comparative trials between the two have been reported to date, however. A retrospective analysis of prospectively, concurrently collected data was performed to compare the outcome and cost of surgery and PTA in the preemptive repair of juxta-anastomotic stenosis in lower forearm AVF. Sixty-four AVF with >50% venous juxta-anastomotic stenosis were considered: 21 were treated surgically (11 proximal neo-anastomosis and 10 polytetrafluoroethylene interposition graft) and 43 by PTA. After treatment, AVF were monitored by quarterly ultrasound dilution access blood flow measurement. End points were restenosis and procedure failure rate (re-intervention by another technique or access loss), and determinants were analyzed using Cox hazard model. Initial procedural success was 100% for surgery and 95% for PTA (P = 0.539). Restenosis rate was 0.168 and 0.519 events/AVF-year for surgery and PTA, respectively (P = 0.009). The type of procedure was the only variable that was significantly associated with restenosis, the adjusted relative risk being 2.77-fold higher (95% confidence interval 1.07 to 7.17; P = 0.036) after PTA than surgery. The procedure failure rate was 0.110 and 0.097 events/AVF-year for surgery and PTA, respectively (P = 0.736). The cost profile also was similar for the two procedures. This prospective comparative study confirms a higher restenosis rate after PTA than surgery, but with strict surveillance for restenosis, the two procedures show similar assisted primary patency and cost, suggesting that they should be considered equally valid, complementary alternatives in the preemptive treatment of juxta-anastomotic stenosis in forearm AVF.

Central role of vasopressin in sodium/water retention in hypo- and hypervolemic nephrotic patients: a unifying hypothesis.

The underfill and overflow hypotheses are usually held as mutually exclusive mechanisms for explaining sodium/water retention in nephrotic syndrome, but neither of them is entirely convincing. In this paper, we will briefly summarize the experimental and clinical evidence in favor of and against each hypothesis. Based on our personal observations, we propose a unifying hypothesis in which underfill and overflow are subsequent stages of the disease. In the transition, a central role is played by vasopressin, which is secreted in the two phases, respectively, by a volume and an osmotic stimulus; therefore, persistent sodium/water retention is maintained through the vascular and tubular effects of this peptide. In addition, we propose that vasodilation and sodium/water excretion could ensue when both stimuli for vasopressin release fade away, leading to the resolution of the syndrome.

Effect of protein leaking BK-F PMMA-based hemodialysis on plasma pentosidine levels.

BACKGROUND: Advanced glycation end-products (AGEs) are now considered to contribute to the middle molecule toxicity of uremia and, because they are not cleared by conventional low-flux hemodialysis, alternative strategies are needed to improve their removal. METHODS: In a prospective cross-over trial involving 18 adult chronic hemodialysis subjects, we evaluated the intradialytic removal and the long-term effect on predialysis levels of Protein-bound (PBPe) and Free (FPe) pentosidine by high-pore, protein-leaking BK-F Polymethylmethacrylate-based hemodialysis (BK-F-HD), by comparing it to hemodialysis using low-flux dialyzers (LF-HD). RESULTS: A single BK-F-HD session removed more PBPe, but not FPe, than LF-HD. Long-term BK-F-HD was associated with a significant decrease in pre-dialysis PBPe, FPe, and albumin (17.7 +/- 20.8, 25.3 +/- 17.3 and 8.0 +/- 3.3%, p<0.01) and no change in body mass index and protein catabolic rate, compared to LF-HD. Multiple stepwise regression analysis identified C-reactive Protein (CRP) (standardized beta coefficient=-0.629), pre-dialysis levels in LF-HD (beta=0.452) and dialysis vintage (beta=0.428) as significant determinants of BK-F-induced changes in predialysis PBPe, and predialysis FPe and PBPe levels in LF-HD as significant determinants of BK-F-induced changes in predialysis FPe (beta=0.720 and 0.286, respectively). CONCLUSIONS: Our study shows that long-term standard diffusive hemodialysis with BK-F membrane reduces predialysis PBPe and FPe levels by comparison with LF-HD, largely due to a greater intradialytic clearance of PBPe. Serum albumin is also reduced without any associated changes in nutritional status markers. The study also suggests that the effect of BK-F-HD in lowering PBPe levels is modulated by the body burden of pentosidine and is blunted or even lost in the presence of elevated CRP levels.

Can blood flow surveillance and pre-emptive repair of subclinical stenosis prolong the useful life of arteriovenous fistulae? A randomized controlled study.

BACKGROUND: Stenosis is the main cause of arteriovenous fistula (AVF) failure. It is unclear, however, if surveillance for stenosis enhances AVF function and longevity and if there is an ideal time for intervention. METHODS: In a 5-year randomized, controlled, open trial we compared blood flow surveillance and pre-emptive repair of subclinical stenoses (one or both of angioplasty and open surgery) with standard monitoring and intervention based upon clinical criteria alone to determine if the former prolonged the longevity of mature forearm AVFs. Surveillance with blood pump flow (Qb) monitoring during dialysis sessions and quarterly shunt blood flow (Qa) or recirculation measurements identified 79 AVFs with angiographically proven, significant (>50%) stenosis. The AVFs were randomized to either a control group (intervention done in response to a decline in the delivered dialysis dose or thrombosis; n = 36) or to a pre-emptive treatment group (n = 43). To evaluate a possible relationship between outcome and haemodynamic status of the access, AVFs were divided into functional and failing subgroups, according to Qa values higher or lower than 350 ml/min or the absence or presence of recirculation. RESULTS: A Kaplan-Meier analysis showed that pre-emptive treatment reduced failure rate (P = 0.003) and the Cox hazards model identified treatment (P = 0.009) and higher baseline Qa (P = 0.001) as the only variables associated with favourable outcome. Primary patency rates were higher in treatment than in control AVFs in both functional (P = 0.021) and failing subgroups (P = 0.005). They were also higher in functional than in failing AVFs in both control (P<0.001) and treatment groups (P = 0.023). Access survival was significantly higher in pre-emptively treated than in control AVFs (P = 0.050), a higher post-intervention Qa being the only variable associated with improved access longevity (P = 0.044). Secondary patency rates were similar in pre-emptively treated and control AVFs in both functional (P = 0.059) and failing subgroups (P = 0.394). They were also similar in functional and failing AVFs in controls (P = 0.082), but were higher in pre-emptively treated functional AVFs than in pre-emptively treated failing AVFs (P = 0.033) or in the entire control group (P = 0.019). CONCLUSIONS: We provide evidence that active blood flow surveillance and pre-emptive repair of subclinical stenosis reduce the thrombosis rate and prolong the functional life of mature forearm AVFs. We also show that Qa is a crucial indicator of access patency and a Qa >350 ml/min portends a superior outcome with pre-emptive action in AVFs.

Diagnostic accuracy of ultrasound dilution access blood flow measurement in detecting stenosis and predicting thrombosis in native forearm arteriovenous fistulae for hemodialysis.

BACKGROUND: Vascular access surveillance by ultrasound dilution blood flow rate (Qa) measurement is widely recommended; however, optimal criteria for detecting stenosis and predicting thrombosis in arteriovenous fistulae (AVFs) are still not clearly defined. METHODS: In a blinded trial, we evaluated the accuracy of single Qa measurement, Qa adjusted for mean arterial pressure (Qa/MAP), and decrease in Qa over time (dQa) in detecting stenosis and predicting thrombosis in an unselected population of 120 hemodialysis subjects with native forearm AVFs (91 AVFs, located at the wrist; 29 AVFs, located at the midforearm). All AVFs underwent fistulography, which identified greater than 50% stenosis in 54 cases. RESULTS: Receiver operating characteristic curve analysis showed that dQa, Qa, and Qa/MAP have a high stenosis discriminative ability with similar areas under the curve (AUCs), ie, 0.961 +/- 0.025, 0.946 +/- 0.021, and 0.912 +/- 0.032, respectively. In the population as a whole, optimal thresholds for stenosis were Qa less than 750 mL/min alone and in combination with dQa greater than 25% (efficiency, 90%); however, the best threshold depended on anastomotic site; it was Qa less than 750 mL/min for an AVF at the wrist and Qa less than 1,000 mL/min for an AVF in the midforearm. Qa was the best predictor of incipient thrombosis (AUC, 0.981 +/- 0.013) with an optimal threshold at less than 300 mL/min (efficiency, 94%). Pooled intra-assay and interassay variation coefficients were 8.2% for MAP, 7.9% for Qa, and 11.2% for Qa/MAP. CONCLUSION: Our study shows that ultrasound dilution Qa measurement is a reproducible and highly accurate tool for detecting stenosis and predicting thrombosis in forearm AVFs. Neither Qa/MAP nor dQa improve the diagnostic performance of Qa alone, although its combination with dQa increases the test's sensitivity for stenosis.

A prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae survival.

Balloon angioplasty (PTA) is an established treatment modality for stenosis in dysfunctional arteriovenous fistulae (AVF), although most studies showing efficacy have been retrospective, uncontrolled, and nonrandomized. In addition, it is unknown whether correction of stenosis not associated with significant hemodynamic, functional, and clinical abnormality may improve survival in AVF. This study was a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access dysfunction improves survival in native, virgin, radiocephalic forearm AVF. Sixty-two stenotic, functioning AVF, i.e., able to provide adequate dialysis, were enrolled in the study: 30 were allocated to control and 32 to PTA. End points of the study were either AVF thrombosis or surgical revision due to reduction in delivered dialysis dose. Kaplan-Meier analysis showed that PTA improved AVF functional failure-free survival rates (P = 0.012) with a fourfold increase in median survival and a 2.87-fold decrease in risk of failure. Cox proportional hazard model identified PTA as the only variable associated with outcome (P = 0.012). PTA induced an increase in access blood flow rate (Qa) by 323 (236 to 445) ml/min (P < 0.001), suggesting that improved AVF survival is the result of increased Qa. PTA was also associated with a significant decrease in access-related morbidity by approximately halving the risk of hospitalization, central venous catheterization, and thrombectomy (P < 0.05). This study shows that prophylactic PTA of stenosis in functioning forearm AVF improves access survival and decreases access-related morbidity, supporting the usefulness of preventive correction of stenosis before the development of access dysfunction. It also strongly supports surveillance program for early detection of stenosis.