Correlation of pre-existing radial artery macrocalcifications with late patency of primary radiocephalic fistulas in diabetic hemodialysis patients.

OBJECTIVE: The aim of this study was to evaluate the impact of pre-existing radial artery macrocalcification (Mönckeberg type of arteriosclerosis) on patency rates of radiocephalic fistulas (RCFs) in diabetic end-stage renal disease (ESRD) patients undergoing hemodialysis. METHODS: In this observational prospective study, the long-term patency rates (primary outcome measures) of RCFs in ESRD diabetics who had Mönckeberg radial (±brachial) artery disease (calcified [C] group) were compared with those obtained in ESRD diabetics who had healthy, noncalcified vessels before RCF construction (healthy [H] group). Vessel calcification was assessed by plain two-dimensional radiography. For inclusion in the C-group, uniform linear railroad track-type macrocalcifications of at least 6 cm in length, in the medial wall of the radial artery ipsilateral to RCF creation, were required. Patients were included in the H-group if the radial artery ipsilateral to the RCF creation was free of any macrocalcification, of either intima or media type. Any intimal-like plaque with irregular and patchy distribution was an exclusion criterion for both groups. Patients in both groups also were required to have suitable upper limb vascular anatomy on the basis of ultrasound imaging before RCF creation (cephalic vein of minimum diameter of 1.6 mm, without stenosis or thrombosis in all outflow areas, and radial artery of minimum diameter of 1.5 mm, without proximal hemodynamically significant stenosis). Secondary outcome measures included all-cause mortality. Kaplan-Meier statistics were used for comparison between groups. RESULTS: The arm radiograph at the site of possible fistula construction showed abnormality in 39 patients (C-group, 47 RCFs), whereas 33 patients had noncalcified ("healthy") vascular anatomy (H-group, 40 RCFs). Mean duration of the diabetic disease at the time of RCF creation was 8.9 ± 5.6 years (range, 2-25 years) for the H-group and 14 ± 9.9 years (range, 1-40 years) for the C-group (P = .018). The mean follow-up period for H-group and C-group was 51.9 ± 35.9 months (range, 0.1-126 months) and 26.1 ± 31.6 months (range, 0.1-144 months), respectively (P = .0006). Forty-four patients died during the follow-up period. Primary patency rates at 12, 24, 36, and 48 months for C-group vs H-group were 50.2% vs 80%, 36.5% vs 72.3%, 32.4% vs 67.9%, and 29.1% vs 59.3% (P = .0019). Respective values for secondary patency rates were 52.4% vs 87.5%, 40.9% vs 82.4%, 36.6% vs 78.1%, and 33.2% vs 72.8% (P = .00064). Patient survival rates at 24 and 48 months were 56.1% and 46.4% for C-group and 92.4% and 67.4% for H-group, respectively (P = .05). CONCLUSIONS: ESRD diabetics with radial artery Mönckeberg calcifications receiving RCFs had worse late clinical outcomes compared with ESRD diabetics with healthy distal arm vessels receiving the same access. The long-term benefit of RCFs may be lost in diabetics with extensively calcified vessels, and preferably the brachial artery should be used instead.

Can dialysis modality influence quality of life in chronic hemodialysis patients? Low-flux hemodialysis versus high-flux hemodiafiltration: a cross-over study.

BACKGROUND: Hemodiafiltration with online preparation of the substitution [online high-flux hemodiafiltration (OHDF)] and hemodiafiltration with prepared bags of substitution (HDF) are important, recently widely used renal replacement therapies in patients with end-stage renal disease. However, there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis (HD) on the quality of life (QoL) of HD patients. This study investigates the effect of dialysis modality on QoL in chronic HD patients. METHODS: In this prospective, randomized, cross-over, open label study, 24 patients were enrolled. Their age were 62 ± 13.34 years (mean ± SD), with the duration of dialysis of 31 ± 23.28 months (mean ± SD). Five of the patients were women. QoL was measured by the Short-Form Health Survey with 36 questions (SF-36) and subscale scores were calculated. Each patient received HD, OHDF, and HDF for 3 months, with the dialysis modality subsequently being altered. They completed the questionnaire of QoL at the end of each period. RESULTS: There were statistical significant differences in QoL for the total SF-36 [36.1 (26.7-45.7) and 40.7 (30.2-62.8)], for classic low-flux HD and high-flux hemodiafiltration, for bodily pain [45 (26.9-66.9) and 55 (35.6-87.5)], and for role limitations due to emotional functioning [0 (0-33.3) and 33.3 (0-100)], respectively. The scores did not differ significantly between the two types of hemodiafiltration. CONCLUSIONS: Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration, on total SF-36, bodily pain, and role limitations due to emotional functioning. Convective modalities may offer better QoL than diffusive HD.

Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis.

Thrombosis is a common complication of end-stage renal disease, particularly in patients on hemodialysis. Although substantial progress has been made in preventing thrombotic complications in various other groups of patients, the mechanisms of thrombosis during hemodialysis require clarification. In this report, we demonstrate that complement activation triggered by hemodialysis biomaterials, and the subsequent generation of the complement anaphylatoxin C5a, results in the expression of functionally active tissue factor (TF) in peripheral blood neutrophils. Because TF is a key initiator of coagulation in vivo, we postulate that the recurring complement activation that occurs during long-term hemodialysis contributes to thrombosis in dialyzed end-stage renal disease patients. Furthermore, we found that complement contributed to the induction of granulocyte colony-stimulating factor, which has been implicated in the pathogenesis of thrombosis in patients treated with the recombinant form of this molecule. Importantly, the inhibition of complement activation attenuated the TF expression and granulocyte colony-stimulating factor induction in blood passing through a hemodialysis circuit, suggesting that the complement system could become a new therapeutic target for preventing thrombosis in patients with chronic renal failure who are maintained on hemodialysis.

Comparison of multiple fluid status assessment methods in patients on chronic hemodialysis.

PURPOSE: Control of hydration status is an important constituent of adequate and efficient hemodialysis (HD) treatment. Nevertheless, there are no precise clinical indices for early recognition of small changes in fluid status of patients undergoing chronic hemodialysis therapy. This study aimed to evaluate and compare the widely used and reliable method of indexed inferior vena cava diameter (IVCDi) with established and more recently available techniques (bioelectrical impedance analysis [BIA], continuous blood volume monitoring [Crit-line], and the B-line score [BLS] with lung ultrasonography) for estimating the hydration status of patients on HD. METHODS: Fifty-three patients undergoing chronic HD thrice weekly were included in the study. Evaluation of hydration status methods (IVCDi, BLS, BIA, and Crit-line) was performed thrice weekly before and after HD. Receiver operating characteristic curve analysis was performed to evaluate the discriminative power of (methods) the BLS, BIA, and Crit-line for predicting over- and underhydration of patients, as determined by the reference method, IVCDi. RESULTS: BLS showed the most promising results in predicting overhydration, as determined by IVCDi, compared with BIA and Crit-line and presented a sensitivity of 77% and specificity of 74%. The accuracy of the BLS was higher than that of BIA (0.81 vs. 0.71, p = 0.032) and Crit-line (0.61, p = 0.001). BLS also showed more promising results in predicting underhydration, as determined by IVCDi, than BIA and Crit-line and presented a sensitivity of 78% and a specificity of 73%. The accuracy of the BLS was higher than that of BIA (0.83 vs. 0.76, p = 0.035) and Crit-line (0.50, p < 0.001). CONCLUSIONS: The BLS is a useful and easily performed technique that has recently become available for accurate evaluation of dry weight and fluid status in patients with end-stage renal disease undergoing chronic HD. This method might help recognize asymptomatic lung congestion in these patients.

Efficient monthly subcutaneous administration of darbepoetin in stable CAPD patients.

BACKGROUND: Although subcutaneous administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients is a widely accepted recommendation, the lowest possible frequency of an efficient dosing regimen remains controversial. Darbepoetin alpha, a new erythropoiesis-stimulating protein with a threefold longer serum half-life compared with rHuEPO, has greater in vivo potency and can be administered less frequently to obtain the same biological response. This study assessed the efficacy of darbepoetin administered once monthly in the treatment of anemia in CAPD patients. PATIENTS AND METHODS: In this single-center, prospective cohort study, 11 stable CAPD patients (5 males, 6 females; mean age 68.8 +/- 14.1 years; mean duration on peritoneal dialysis 31.6 +/- 13 months) maintained average hemoglobin and hematocrit levels of 12.09 +/- 1.29 g/dL and 37.29% +/- 3.58%, respectively, while receiving a mean weekly maintenance dose of epoetin alfa of 129 IU/kg. These same patients were assigned to receive the equivalent weekly darbepoetin dose once monthly for 24 consecutive weeks. Hematological response, iron status (transferrin saturation, serum ferritin levels), C-reactive protein (CRP), and the patients' biochemical profiles were evaluated monthly. RESULTS: During the monthly administration of darbepoetin, mean serum levels of Hb and Hct were 12.17 +/- 1.28 g/dL and 37.1% +/- 1.19% respectively. No statistically significant difference was apparent between the previous and monthly dosing values (12.09 +/- 1.29 vs 12.17 +/- 1.28 g/dL, p = 0.769, and 37.29% +/- 3.58% vs 37.1% +/- 1.19%, p = 0.752). Transferrin saturation levels as well as serum ferritin levels also remained unchanged (30.4% +/- 8.6% vs 30.1% +/- 9.4%, NS, and 556 +/- 212 vs 621 +/- 234 ng/mL, respectively, NS). CONCLUSION: These results indicate that darbepoetin alfa can be effectively given subcutaneously at monthly intervals for the treatment of anemia in stable CAPD patients. However, more studies are needed to validate the long-term efficacy of this monthly subcutaneous administration.

Peritoneal catheters and related infections.

Catheter related infectious complications (exit-site infections, tunnel infections, and peritonitis) remain the major reasons for technique failure during the three decades since, continuous ambulatory peritoneal dialysis (CAPD) treatment has been first established. Despite improvements in catheter's survival rates, catheter related complications result in an increase in the cumulative patients' morbidity and often leading to the catheter removal. The ideal catheter provides reliable and rapid dialysate flow rates without leaks or infections. Among several types, the double-cuff straight Tenckhoff catheter, developed in 1968, is still the most widely used, although its use is decreasing in favour of swanneck catheters. Although there are only few well-designed trials comparing catheters and catheters related infectious complications, controlling for all other important variables, no difference in these complications among the main types of catheters was seen. The single cuff catheters have been associated with a shorter survival rate and time to the first peritonitis episode than the double-cuff catheters. Also exit-site infections were found to be more frequent and significantly more resistant to treatment with single-cuff compared to double-cuff ones. Finally, better results have been reported with the latest developed presternal peritoneal dialysis catheter both regarding survival rates and exit-site infection and peritonitis rates. Recently a renewed interest in continuous flow peritoneal dialysis stimulated inventions of imaginative, double-lumen catheters since a suitable peritoneal access is a sine qua non condition for the development of this new technique of peritoneal dialysis.

Vascular access for hemodialysis: postoperative evaluation and function monitoring.

Vascular access (VA) survival is a crucial issue associated with morbidity and mortality of patients undergoing maintenance hemodialysis. The development of stenosis is the major factor that leads to VA failure. Strategies for early detection of lesions within a VA system before serious complications arise are therefore crucial. The implementation of a VA surveillance program could lead to timely detection of VA dysfunction and referral for correction, reduction in central venous catheter use and decrease in hospitalization and VA-related cost. Suggested methods for arteriovenous fistulae and grafts surveillance include blood flow measurement, static pressure evaluation and duplex ultrasonography. Physical examination is an accepted method in contrast to nonstandardized dynamic pressure measurement for grafts. Access recirculation (not urea based) and dynamic pressure measurements are accepted methods for fistulae. Decreasing URR or Kt/V (otherwise unexplained) and increased (negative) arterial pressure in the dialysis machine are methods of limited sensitivity and specificity for both fistulae and grafts. Measurement of access blood flow has been proposed as the gold standard for the screening of all types of VA. Access flow can be measured by various techniques which are direct or indirect. Several studies about VA surveillance programs have demonstrated conflicting results. Larger, randomized controlled trials need to be carried out in order to clarify whether surveillance programs are necessary and which is the best surveillance strategy for each type of VA.

Metformin-related lactic acidosis in patients with acute kidney injury.

BACKGROUND: Metformin is nowadays considered as first-line therapy in individuals with non-insulin dependent diabetes mellitus (NIDDM). Metformin-related lactic acidosis (MALA) occurs more frequently after inappropriate use especially in patients with acute kidney injury (AKI) or chronic kidney disease (CKD). Thus, its prescription in these patients is contraindicated, while the role of dialysis is under evaluation. METHODS: We describe two cases of severe metformin-related lactic acidosis with underlying acute kidney injury, which were treated with dialysis. RESULTS: In both cases, lactic acidosis occurred on a background of acute decline in renal function, possibly due to drug accumulation. It is interesting that metformin was contraindicated in one case. CONCLUSION: Lactic acidosis is a rare but potentially fatal adverse effect of metformin, particularly in patients with AKI, which should always be considered in clinical practice. Dialysis seems to contribute significantly to the management of this life-threatening condition and the improvement in outcome.

A hybrid approach to salvage a failing long-standing autogenous aneurysmal fistula in a hemodialysis patient.

Very few studies have addressed the repair of autogenous and prosthetic-related false arteriovenous access (AVA) aneurysms in hemodialysis patients. Surgical management of complicated AVA-related aneurysms remains the gold standard method although covered stents have recently been introduced for the exclusion of such aneurysms, offering a minimally invasive therapy. In this paper, we describe a combination of open and endovascular repair for treating an anastomotic and a puncture-site aneurysm to salvage a failing long-standing autogenous radial-cephalic fistula in the wrist. Resection of the anastomotic aneurysm and reconstruction of the anastomosis proximally was initially performed. Via the first cm of the anastomosis, a Fluency® stent graft (SG) was inserted and it successfully excluded the mid-outflow vein false aneurysm. Such hybrid therapies may be the future of AVA revisions and this trend should not be overlooked by nephrologists and vascular surgeons.

Surgical revision of complicated false and true vascular access-related aneurysms.

PURPOSE: This prospective observational study examined the effect of revision surgery in patients who present solely with complicated arteriovenous access (AVA)-related aneurysms. METHODS: The demographics and comorbid conditions of 44 hemodialysis access patients who presented with complicated true or false AVA-related aneurysms and underwent revision surgery during a 7-year period were prospectively entered into our AVA database. Also recorded were AVA characteristics before and after revision. Arteriovenous access anatomy was evaluated preoperatively using color Doppler ultrasonography, and AVA adequacy was assessed in all patients postoperatively after the first needle puncture and every month thereafter. Postintervention access function and primary patency rates were analyzed. Patency was evaluated using the Kaplan-Meier method and compared between groups of patients with different AVA characteristics before and after revision using the log-rank test. RESULTS: The cases of initial AVA with complicated aneurysms comprised 16 radiocephalic, 8 brachiocephalic, 2 basilic vein transposition, and 18 prosthetic fistulas (7 and 11 of the lower and upper arm, respectively), of which 42 were dysfunctional and 2 had thrombosed early at presentation. Primary indications for revision were danger of aneurysm rupture in 26, duplication in graft aneurysm diameter in 18, painful aneurysm in 12, stenosis due to partial aneurysm thrombosis in 12, shortness of the potential cannulation area in 12, aneurysm enlargement in 4, infected aneurysm in 2, and completely thrombosed aneurysm in 2. The mean postintervention primary patencies were 93%, 82%, 57%, and 32% at 3, 6, 12, and 24 months, respectively. The outcomes was better in autogenous than prosthetic corrections, in true than false aneurysms, in patients with two or fewer than more than 2 previous AVAs on revised arms, and in forearm than upper-arm corrections (P = .0197, P = .004, P = .0022, and P = .0225, respectively). CONCLUSIONS: Surgical revision of complicated false and true AVA-related aneurysms reveals acceptable postintervention primary patency rates and therefore is justified. This outcome measure was superior in the following specific groups of corrections: autogenous were better than prosthetic, true aneurysms were better than false aneurysms, patients with one or two previous AVAs in the revised arm were better than those with more than two previous accesses in the revised arm, and finally, forearms were better than those in the upper arm.

Use of short PTFE segments (<6 cm) compares favorably with pure autologous repair in failing or thrombosed native arteriovenous fistulas.

OBJECTIVE: The re-establishment of patency in a stenosed or thrombosed native arteriovenous fistula (AVF) is fundamental to regaining adequate hemodialysis through the same cannulable vein. Many surgeons have been reluctant to use even small segments of synthetic grafts in AVF revisions because of a perception that these would lead to poor results; however, studies comparing various treatment options are scarce. This study compared the use of short (<6 cm) polytetrafluoroethylene (PTFE) segments with pure autologous repair in stenosed or thrombosed native fistulas. METHODS: The cumulative postintervention primary patency rates of two groups of hemodialysis patients receiving different surgical revision operations of their vascular accesses were prospectively compared. Group I (n = 30) comprised patients who presented with stenosed or thrombosed native fistulas and received short (2 to 6 cm) interposition PTFE grafts placed after the stenosed or thrombosed outflow vein segment was resected. These short PTFE grafts were not used for cannulation. Group II (n = 29) comprised patients who presented with dysfunctional or failed AVFs and underwent various types of pure autogenous corrections. AVF dysfunction or thrombosis was detected with clinical examination and color duplex ultrasound scanning. In all cases, on-table arteriography-fistulography was performed before surgical repair. Access adequacy was assessed in all patients postoperatively after the first puncture and every month thereafter (mean follow up 16.7 months). RESULTS: No statistically significant difference in patency was observed between the two groups. Postintervention cumulative patencies were 100%, 88%, and 82% for group I and 90%, 82%, and 71% for group II at 6, 12, and 18 months, respectively ( P = .8). CONCLUSIONS: Short (<6 cm) interposition PTFE segments used for the revision of failing or failed AVFs compare favorably to purely native repair and do not alter the autologous behavior of the initial access. These short PTFE revisions resulted in satisfactory midterm primary patency without further consumption of the venous capital by harvesting segments of vein from other locations and without compromising more proximal access sites. This practice is recommended and is justified as part of an aggressive access salvage policy addressed by many authors so far.

Effects of hemodialysis dose on anemia, hypertension, and nutrition.

There is good evidence that by improving dialysis adequacy, morbidity, and mortality of hemodialysis (HD) patients decrease. Dialysis adequacy has also been related to the better control of arterial blood pressure (BP), anemia and improvement of patients' nutritional status. This is a self-control study of 34 HD patients, (23 males, 11 females), aged 52.6 +/- 15.5 years, HD duration 55.9 +/- 61.2 months, referring to the effect of increasing delivered dialysis dose, over a two-year period, on their clinical and laboratory parameters. Delivered HD dose increased statistically significantly: Urea reduction ratio (URR) increased from 52 +/- 8 to 71 +/- 7% and Kt/V from 0.93 +/- 0.19 to 1.55 +/- 0.29 (p < 0.001). Hb increased statistically significantly from 10.4 +/- 1.7 to 11.0 +/- 1.3 g/dL (p < 0.05) while no difference has been noticed in weekly EPO dose. Both systolic and diastolic BP decreased statistically significantly (from 147 +/- 24 to 133 +/- 25mmHg and from 73 +/- 12 to 66 +/- 13 mmHg respectively, p = 0.001). Serum albumin increased from 4.3 +/- 0.4 to 4.6 +/- 0.3g/dL (p = 0.002) and nPCR from 0.93 +/- 0.16 to 1.20 +/- 0.17 (p < 0.001). We conclude that increasing dialysis dose results in both clinical and laboratory improvement regarding hypertension, nutritional status and control of HD patients' anemia.

The Clinical Impact of Increasing the Hemodialysis Dose.

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2-year period, the present self-controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry-weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/Vurea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred-to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)-with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/Vurea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry-weight policy, resulted in improvements in hypertension, nutritional status, and anemia.

The Progression of Uremic Polyneuropathy in Patients on Hemodialysis and Hemofiltration: A Two-Year Study.

Uremic polyneuropathy is one of the major complications of long-term end-stage renal disease. In the present study, we performed an electrophysiologic evaluation in 17 patients having a mean age of 49 ± 11 years. The patients were divided into two groups according to dialysis method. Group A included 9 patients who were undergoing conventional hemodialysis (mean age, 44.2 ± 12.5 years; mean duration on dialysis, 21.7 ± 4.3 months); group B included 8 patients undergoing hemofiltration (mean age, 55.2 ± 5.2 years; mean duration on treatment, 27 ± 7.6 months). Measurements of the distal latency time of the sensory fibers (median, ulnar, and sural nerves), and measurements of the distal latency time and peripheral conduction velocity of the motor fibers (median and peroneal nerves) were performed. In addition, we recorded somatosensory evoked potentials after peripheral stimulation of the median and peroneal nerves. The electrophysiologic evaluations were repeated two times at intervals of 12 months. In group A, a statistically significant worsening of motor and sensory conductance in the upper and lower limbs was observed; in group B, a statistically significant improvement was found. These findings suggest that hemofiltration has a more beneficial effect on motor and sensory conductivity than does conventional hemodialysis.

Lipoprotein abnormalities in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Lipid abnormalities are important variables in the development of vascular atherosclerotic lesions in ESRD patients while Lp(a) represents an independent risk factor. In order to evaluate lipid changes in HD and CAPD patients, serum cholesterol (TC), HDLc, LDLc, TG, apolipoproteins (AI,AII,B,E), Lp(a), and albumin levels were estimated in 109 ESRD dialyzed patients, 46 in HD and 63 in CAPD (mean duration 50 +/- 40 and 25 +/- 19 months, respectively), and 45 volunteers with high serum levels of C and TG, without renal insufficiency. Both HD and PD group revealed statistically significantly higher levels than controls for TC, TG, LDL-C, Apo-B,-E, while HDL-C levels were significantly lower. Except for the lower serum albumin levels in both dialyzed groups after six months lower ApoAI levels and higher ApoB levels were observed in HD and PD patients respectively. Lp(a) levels remained unchanged in HD group, while a statistically significant increase appeared in PD patients that was negative correlated with the decreased serum albumin levels. These results indicate that renal replacement modalities result in a different effect in lipoprotein metabolism that may play an important role in atherosclerotic vascular disease of dialyzed ESRD patients.