Abstract: Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular diseases than the general population. Endothelial dysfunction, which participates in accelerated atherosclerosis, is a hallmark of CKD. Patients with CKD display impaired endothelium-dependent vasodilatation, elevated soluble biomarkers of endothelial dysfunction, and increased oxidative stress. They also present an imbalance between circulating endothelial populations reflecting endothelial injury (endothelial microparticles and circulating endothelial cells) and repair (endothelial progenitor cells). Endothelial damage induced by a uremic environment suggests an involvement of uremia-specific factors. Several uremic toxins, mostly protein-bound, have been shown to have specific endothelial toxicity: ADMA, homocysteine, AGEs, and more recently, p-cresyl sulfate and indoxyl sulfate. These toxins, all poorly removed by hemodialysis therapies, share mechanisms of endothelial toxicity: they promote pro-oxidant and pro-inflammatory response and inhibit endothelial repair. This article (i) reviews the evidence for endothelial dysfunction in CKD, (ii) specifies the involvement of protein-bound uremic toxins in this dysfunction, and (iii) discusses therapeutic strategies for lowering uremic toxin concentrations or for countering the effects of uremic toxins on the endothelium.

Abstract: Residual renal function (RRF) is well recognized as an important marker of outcomes in peritoneal dialysis (PD), and contributes vitally to solute clearance. Recently, its importance in hemodialysis (HD) has emerged with evidence that it is strongly associated with improved outcomes. The presence of RRF is associated with improved nutrition, reduced erythropoetin requirements, better potassium clearance, and improved quality of life. Retrospective and observational evidence is now available, which suggests that the presence of RRF is independently associated with survival and that this benefit goes beyond what is expected simply from augmentation of small solute clearance. Preservation of RRF is now considered by many to be an important aspect of dialysis strategy. Evidence in favor of one modality over another for preservation of RRF is conflicting, as are the potential benefits of biocompatible fluids in PD. In HD, the evidence in favor of biocompatible membranes is stronger. Emerging evidence is broadly in favor of angiotensin converting enzyme inhibitors for preservation of RRF. Diuretics appear to have a neutral effect. The complexities and practical difficulties in measurement of RRF have resulted in this important parameter being largely ignored in HD. Novel markers of renal function may provide alternative, simple methods of estimating RRF, which may remove the need for urine collections and simplify its measurement.

Abstract: Fatigue is common in chronic hemodialysis (HD) patients and impacts on daily living, impairs significantly the quality of life, increases the risk of cardiovascular events and negatively influences survival. Although numerous social, demographic, clinical, and laboratory variables have been associated with fatigue, the causes of this symptom are often unclear. In the absence of an underlying, treatable disorder, the results of therapeutic intervention are typically frustrating. So far, none of the drugs tested can be recommended for preventing and treating fatigue in chronic HD patients. There is some evidence that exercise may significantly improve fatigue in dialysis patients; however, this requires confirmation through large, prospective, randomized studies.

Abstract: Dialysis-dependent chronic kidney disease (CKD) is an expanding problem for healthcare systems worldwide. The prevalence of end-stage renal disease (ESRD) has increased by 20% since 2000 and stands at 1699 per million people in the USA. ESRD is associated with an increased risk of cardiovascular comorbidity, increased severity of cardiovascular disease, and an adjusted all-cause mortality rate that is 6.4-7.8-fold higher than the general population. These patients may present electively or emergently for surgery related to, or remote from, the CKD. In any perioperative setting, the patient with hemodialysis-dependent CKD represents a significant clinical challenge, and successful management of these patients requires effective cooperation and communication between nephrology, anesthesia, and surgical staff. The ESRD patient's nephrologist will have the best knowledge of their medical history, comorbidities, and future management goals and may have been the clinician who instigated the referral for the surgery, e.g., for parathyroidectomy, vascular access surgery, nephrectomy or renal transplantation. As such, they are in an ideal position to contribute to, or coordinate, early preoperative medical optimization of the patient and also to provide advice during postoperative recovery and rehabilitation. In this article, we provide an overview of some of the key aspects of managing these patients successfully during the perioperative period. We propose the integration of cardiopulmonary exercise testing and cardiovascular optimization into the care of these high-risk patients and provide an overview of the importance of maintaining microvascular perfusion and the role of viscosity in preserving the capillary perfusion network.

Abstract: The disease spectrum leading to pediatric renal replacement therapy (RRT) provision has broadened over the last decade. In the 1980s, intrinsic renal disease and burns comprised the most common pediatric acute renal failure etiologies; more recent data demonstrate that pediatric acute kidney injury (AKI) most often results from complications of other systemic diseases resulting from the advancements in congenital heart surgery, neonatal care, and bone marrow and solid organ transplantation. In addition, RRT modality preferences to treat critically ill children have shifted from peritoneal dialysis to continuous renal replacement therapy (CRRT) as a result of improvements in CRRT technologies. In this article, we aim to review the pediatric specific causes for RRT provision, emphasizing the emerging practice patterns with respect to modality and timing of treatment. We will focus on the application of different RRT modalities and related outcome of children with AKI who receive RRT.

Abstract: The present review is aimed at illustrating and discussing literature data and recent guidelines concerning artificial nutrition in patients with acute kidney injury (AKI) on renal replacement therapy (RRT). Protein-energy wasting often complicates the clinical course of AKI in critically ill patients, increasing their morbidity and mortality risk. The most severe forms of the syndrome - those observed in ICU patients - are characterized by hypercatabolism with relevant lean body mass loss. In this clinical condition, artificial nutrition (enteral and/or parenteral nutrition) is considered an integral part of the complex therapeutic approach. Even though many issues concerning nutrition in AKI are common to other critically ill patients, the presence of AKI with the ensuing impairment of the kidney homeostatic function introduces specific problems and can make more difficult to give the patient an adequate nutrient provision. Thus, peculiarities of the syndrome - and of RRT itself - must be taken into account in nutritional planning for these patients. Recent guidelines have suggested that the enteral route should be the preferred one, even though parenteral nutrition is often required to target nutritional needs (25-30 kcal/kg body weight/day, and 1.5 + 0.2 g/kg/day to compensate for amino acid losses during RRT). Special attention should be paid to the impact of different forms of RRT on the possible loss of both macro- and micronutrients and vitamins, as well as to the risk of metabolic complications. Finally, close integration between nutritional support and RRT is required, aiming at carefully tailoring both therapies on patient's changing needs.

Abstract: Vancomycin has been a cornerstone antibiotic for the treatment of severe gram-positive infections in dialysis patients for decades. Whereas subtherapeutic vancomycin levels convey a risk of treatment failure and the further emergence of resistance in staphylococci, supratherapeutic vancomycin levels are associated with a dose-related incremental risk for nephrotoxicity and ototoxicity. Consequently, a narrow therapeutic range with a trough-level target between 15 and 20 μg/ml is recommended. Vancomycin dosing in hemodialysis patients is mainly influenced by the timing of administration (during or after dialysis), the type of filter used, and the duration of dialysis. Actual body weight, the interdialytic interval, and residual renal function are also considerations. As in patients with normal kidney function, a weight-based loading dose of 20-25 mg/kg should be used in dialysis patients. While most fixed-dose maintenance regimens fail to reach target levels in the majority of hemodialysis patients, straightforward evidence on optimal maintenance dosing is lacking.

Abstract: Renal replacement therapies (RRTs) are frequently employed for treatment of patients suffering from acute kidney injury in the intensive care unit (ICU). Multiple modalities of RRT are currently available. These include intermittent hemodialysis, continuous renal replacement therapies, and hybrid therapies, such as sustained low-efficiency dialysis. Because of the high complexity of ICU patients, physicians must be aware of the limitations and complications of both intermittent and continuous dialysis modalities that can contribute to patient morbidity and mortality. In this article, we highlight the recognized complications of RRTs and the treatment approach to these complications.

Abstract: As dialytic practice has evolved, hemodialysis (HD) adequacy has come to be defined in terms of small molecule clearance. A growing body of evidence suggests that fluid dynamics, specifically ultrafiltration rate (UFR), bear clinical and physiological significance and should perhaps play a more central role in titrating HD therapy. Three recent studies have shown an independent association between higher UFR and mortality. Further work is needed to determine whether this relationship represents a direct toxic effect of rapid fluid perturbations or whether this association is a consequence of confounding on the basis of large interdialytic weight gain, as each would prompt a different therapeutic response. This mounting evidence builds the case that fluid management should play a more central role in the dialytic prescription and that more individualized approaches to fluid management should be encouraged.

Abstract: Thrombosed immature fistulas have historically been considered unsalvageable. However, advances in procedure and balloon catheter technologies have expanded the scope of endovascular treatments. This study investigates the efficacy, functionality, and cost associated with the use of percutaneous techniques for the salvage of thrombosed immature fistulas. Over a 2-year period and from a population of 18,000 patients on hemodialysis, 140 consecutive patients with thrombosed immature fistulas underwent attempts at salvage via thrombectomy procedures. All fistulas had thrombosed following access creation and had never been used for hemodialysis. Multiple approaches were utilized to gain access to the fistula, including trans-fistula cannulation, distal arterial puncture, and proximal retrograde venous access. Thrombectomy was performed via balloon maceration and aspiration. Accelerated maturation was achieved through sequential angioplasty of diffusely stenotic veins and elimination of competing branch vessels. Primary access, primary assisted, and secondary access patencies were calculated at 3, 6, 12, and 24 months. A cost analysis was performed based on procedure statistics and the 2009 Medicare reimbursement schedule and compared with data from the 2009 United States Renal Data Survey. Thrombectomy was successful in 119 (85%) immature clotted fistulas, and hemodialysis adequacy was achieved in 111 (79%) fistulas. The average maturation time from thrombectomy to cannulation for dialysis was 46.4 days, with an average of 2.64 interventions per patient. There were 5 (3.5%) cases of angioplasty-induced rupture, all of which were treated with stent placement. Clinically significant pseudoaneurysm formation occurred in 4 (2.8%) patients. At 12 months, secondary access patency of salvaged accesses was 90%. Based on 2009 Medicare outpatient billing rates per patient per initial access-year and the maturation times observed in the New York area, percutaneous salvage of thrombosed immature fistulas costs $4881 to $14,998 less than access abandonment and new access creation. Endovascular techniques can be used for the salvage of thrombosed nonmaturing fistulas. When analyzed within the initial access-year, this approach yields significant cost savings over access abandonment.

Abstract: Adequate dialysis is difficult to define because we have not identified the toxic solutes that contribute most to uremic illness. Dialysis prescriptions therefore cannot be adjusted to control the levels of these solutes. The current solution to this problem is to define an adequate dose of dialysis on the basis of fraction of urea removed from the body. This has provided a practical guide to treatment as the dialysis population has grown over the past 25 years. Indeed, a lower limit to Kt/V(urea) (or the related urea reduction ratio) is now established as a quality indicator by the Centers for Medicare and Medicaid for chronic hemodialysis patients in the United States. For the present, this urea-based standard provides a useful tool to avoid grossly inadequate dialysis. Dialysis dosing, however, based on measurement of a single, relatively nontoxic solute can provide only a very limited guide toward improved treatment. Prescriptions which have similar effects on the index solute can have widely different effects on other solutes. The dose concept discourages attempts to increase the removal of such solutes independent of the index solute. The dose concept further assumes that important solutes are produced at a constant rate relative to body size, and discourages attempts to augment dialysis treatment by reducing solute production. Identification of toxic solutes would provide a more rational basis for the prescription of dialysis and ultimately for improved treatment of patients with renal failure.

Abstract: The current definition of a significant stenosis in an autologous arteriovenous fistula (aAVF), the percentage narrowing compared with the adjacent "normal" vessel, is inaccurate. We believe a significant stenosis in the aAVF is an absolute minimal luminal diameter determined by the requirements of the hemodialysis pump. To determine what absolute diameter constitutes a hemodynamically significant stenosis in a radio-cephalic autologous arteriovenous fistula (RC aAVF), the minimal luminal diameter of dysfunctional RC aAVF was compared to that of functional RC aAVF using grayscale and color ultrasound. There were 93 fistulas in study group and 77 in control group. The mean minimum luminal diameter in study group was significantly lower than in control group (2.19 vs. 4.71 mm, p 0.001). With a cutoff value of 2.7 mm, there was 90% sensitivity and 80% specificity in distinguishing functional fistula from dysfunctional fistula. The area under the receiver-operator curve was 90% (CI 84-94%), indicating that a 2.7 mm diameter is accurate in discriminating functional from dysfunctional fistulas. An absolute minimal luminal diameter of 2.7 mm, as determined with grayscale and color ultrasound, is a useful cutoff for defining significant stenosis in a RC aAVF.

Abstract: Currently, high-flux hemodialysis is the most common mode of dialysis therapy worldwide. Its steadily increasing use is largely based on the desire to reduce the excessively high morbidity and mortality of end-stage renal disease patients maintained on conventional dialysis (low-flux, mostly cellulosic membranes) by offering better biocompatibility and enhanced removal of uremic toxins. Two large randomized trials suggest a survival benefit for selected subgroups of high-flux dialysis patients such as diabetics, patients with hypoalbuminemia, or patients who have been on dialysis for a long period (>3.7 years). The major disadvantage of high-flux hemodialysis relates to the use of dialysis fluid, which is commonly not pure and may endanger patients treated with high-flux hemodialysis. Endotoxin fragments and other bacterial substances derived from bacteriologically contaminated dialysis fluid may, even at bacterial counts or endotoxin concentrations within the limits of accepted standards of dialysis fluid purity, enter from the dialysate into the patient's blood either by convective transfer (backfiltration) or by movement down the concentration gradient (backdiffusion). Repeated exposure of high-flux hemodialysis patients to backtransport of dialysate contaminants aggravates the uremia-associated inflammatory response syndrome and contributes to long-term morbidity. At present, the only solution to circumvent the risks of backtransport is the use of dry powder cartridges for bicarbonate concentrate and the use of bacteria- and endotoxin-retentive filters for the online production of ultrapure dialysis fluid. Use of ultrapure dialysis fluid (bacteria <0.1 CFU/ml and endotoxin <0.03 IU/ml) has been found to reduce inflammation and comorbidities in clinical investigations compared to commercial dialysis fluid. The European Renal Association and a number of national societies in Europe or in Japan strongly recommend the use of ultrapure dialysis for high-flux hemodialysis.

Abstract: Peritoneal dialysis (PD) is a simple, safe, gentle, and efficient renal replacement therapy (RRT) method. It is able to correct acute kidney injury (AKI)-induced metabolic, electrolytic, and acid-base disorders and volume overload both in and out the intensive care unit setting. Some PD modalities, such as high-volume PD and continuous flow PD, can provide RRT doses and efficiency comparable to extracorporeal blood purification methods. PD is particularly suitable for children, patients with refractory heart failure or hemodynamically instable, conditions where systemic anticoagulation should be avoided, patients with difficulty for vascular access and hypo- and hyperthermia conditions. In the following manuscript, PD technical aspects and the possible advantages and limitations of this RRT method will be discussed, and the more recent literature on clinical experience with PD for treatment of AKI will be reviewed.

Abstract: Acute kidney injury (AKI) is now well recognized as an independent risk factor for increased morbidity and mortality particularly when dialysis is needed. Although renal replacement therapy (RRT) has been used in AKI for more than five decades, there is no standard methodology to predict which AKI patients will need dialysis and who will recover renal function without requiring dialysis. The lack of consensus on what parameters should guide the decision to start dialysis has led to a wide variation in dialysis utilization. A contributing factor is the lack of studies in the modern era evaluating the relationship of timing of dialysis initiation and outcomes. Although listed as one of the top priorities in research on AKI, timing of dialysis initiation has not been included as a factor in large, randomized controlled trials in this area. In this review we will discuss the criteria that have been used to define early vs. late initiation in previous studies on dialysis initiation. In addition, we propose a patient-centered approach to define early and late initiation that could serve as framework for managing patients and for future studies in this area.

Abstract: Over the past decade, patients returning to dialysis after a failed transplant comprised of 5-10% of the annual number of dialysis initiations in the United States, whereas retransplant candidates account for 5.0-13% of the annual deceased donor wait-list additions. The United States Renal Data System (USRDS) database revealed a >3-fold increase in the annual adjusted death rates for patients returning to dialysis after graft loss compared with patients with a functioning allograft (9.4% vs. 2.8%, respectively). Continuation of low-dose immunosuppression to maintain residual allograft function has been suggested as a contributing factor, presumably via treatment-related infectious and cardiovascular complications among others. In contrast, a survival advantage in maintaining patients on long-term immunosuppression after returning to peritoneal dialysis has also been suggested. Despite the significant number of patients requiring reinitiation of some form of renal replacement therapy after a failed transplant and the increasing evidence suggesting their high mortality and morbidity rates, management of the failed allograft in these patients has received little attention. This article presents an overview of the literature on the management of immunosuppression after allograft failure, a brief review on the pros and cons of allograft nephrectomy, and the authors' opinions on the management of immunosuppression in patients with a failed kidney allograft.

Abstract: Numerous reports in the general and the dialysis population have shown associations of sodium (Na(+)) intake, blood pressure, and survival. In addition to dietary Na(+) intake, positive Na(+) balance during dialysis needs to be considered as a source of Na(+). Dialysate Na(+) (DNa(+)) concentrations above the serum Na(+) concentration (SNa(+)) result in diffusive Na(+) flux from the dialysate into the patient, which has recently been reported to be associated with increased interdialytic weight gain and mortality. Individualization of the Na(+) prescription and Na(+) alignment (DNa(+) equal to SNa(+)) prevents positive Na(+) balance and improves patient outcomes. Alignment requires the knowledge of patients' SNa(+), which can be estimated from previous SNa(+) in the monthly routine laboratory measurements. Na(+) alignment was recently implemented in a dialysis clinic of Renal Research Institute. Preliminary results of this initiative have shown a trend of predialysis weight and blood pressure reduction. Expansion of this initiative to all clinics of RRI is currently underway and as of April 2011, four additional clinics have been included. Additional research on adequate Na(+) alignment is needed to account for Gibbs-Donnan effects, differences in charge across the dialyzer membrane, and variability in measurement methods. Regular calibration of DNa(+) delivery by dialysis machines is necessary to ensure that the dialysis prescription is followed. How to provide dialysis to severely hyponatremic patients remains an open question. Finally, long-term studies of the effects of Na(+) restriction on hospitalization and mortality are required to demonstrate the benefits of aligning DNa(+) with SNa(+).

Abstract: To elucidate the source of neointimal cells, experimental fistulas were created in Lewis wild-type (WT) and transgenic rats that constitutively expressed the green fluorescent protein (GFP) in all tissues. Arteriovenous fistula (AVFs) were created by anastomosing the left renal vein to the abdominal aorta. The contribution of bone marrow (BM)-derived cells to the AVF neointima was examined in lethally irradiated WT rats that had been rescued with GFP BM cells. Neointimal cells in these chimeric rats were mostly GFP negative indicating the non-BM origin of those cells. Then, the contribution of arterial cells to the AVF neointima was assessed in a fistula made with a GFP aorta that had been implanted orthotopically into a WT rat. Most of the neointimal cells were also GFP negative demonstrating that AVF neointimal cells are not derived from the feeding artery. Finally to study local resident cells contribution to the formation of neointimal lesions, a composite fistula was created by interposing a GFP vein between the renal vein and the aorta in a WT recipient rat. GFP neointimal cells were only found in the transplanted vein. This study suggests that neointimal cells originate from the local resident cells in the venous limb of the fistula.

Abstract: The methodology, prescription, and delivery of acute renal replacement therapy are rapidly evolving areas. Recent clinical trials have provided clearer guidance around dosing targets for both therapy prescription and delivery. In this article, we discuss dialysis efficiency which is an area that subserves dialysis dose and pertains to manner in which a given dose is delivered. Dialysis efficiency directly effects the measurement and calculation of dose, and the occurrence of dialysis disequilibrium and hemodynamic instability. We provide recommendations around selecting the most appropriate clinical scenario and patients for higher-efficiency versus lower-efficiency therapy, and the implementation of therapy to achieve a given efficiency.

Abstract: The need for early cannulation grafts exists to prevent use of central venous catheters. We report our experience in patients who had a straight axillo-axillary angioaccess. All patients who have undergone an early cannulation axillo-axillary angioaccess between 2008 and 2010 were reviewed. Fifteen patients had 16 procedures. Of these, eight were women and their mean age was 56. All patients had exhausted access options bilaterally. All had previous catheter insertions with either sepsis or jugular veins thrombosis. They all had an axillary artery to axillary vein angioaccess using an early cannulation graft. Flixene(®) (Atrium Medical, Hudson, NH, USA) was used in 10 cases, whereas Rapidax(®) (Vascutek Ltd., Renfrewshire, UK) in 6. In 12 cases, grafts were cannulated after 12 hours, in 4 after 24 hours (12 hours-8 days, mean 1.8 days). For Flixene(®) , mean delay to cannulation was 1.1 days, whereas 2.71 for Rapidax(®) (p < 0.05). Primary patency rates were 92.9% and 65.7% at 6 weeks and 1 year, respectively. Secondary patency rates were 92.9% and 83.5%. There was no significant difference in patency rates between grafts. Early cannulation grafts in a complex position are safe and efficient considering their patency and complication rates. It avoids using central venous catheters.

Abstract: After early strong support, home hemodialysis (HHD) has all but disappeared as a viable modality in most western countries--except in Australia and New Zealand (ANZ), where a mean 12.9% of all HD (June 2010) is home-based. The reasons for this unique difference are neither demographic nor geographic; rather, they result from a strong belief held by ANZ nephrologists, nurses, and funding agencies in the clinical outcome and economic benefits of HHD. This "hemodialysis is best at home" approach has permitted ANZ programs to take full advantage of a renewed interest in extended hour and higher frequency dialysis. This article explores the reasons for the success of HHD in this region.

Abstract: Data derived from a large cohort of hemodialysis patients (12,896) undergoing dialysis access maintenance procedures being performed by interventional nephrologists were analyzed to determine the safety of sedation/analgesia (S/A) in a freestanding facility. Data collected included patient demographics, procedures performed, time of procedures, drugs used, doses used, and complications that occurred. Four high-risk groups were identified based upon age, pulmonary status, and over all physical status. These were compared to the total cohort. Midazolam, fentanyl, or a combination of the two were used. Within the total cohort of patients, midazolam alone was used most commonly (94.7%). The total mean dose of midazolam when used alone was 3.4 mg. The dosages used in the high-risk groups tended to be only slightly lower (3-3.2 mg). This setting appears to be safe for hemodialysis patients, even those in high-risk subgroups having these types of procedures. The types of drugs and the dosages that are commonly used do not appear to be associated with an unacceptable risk to the hemodialysis patient. A nephrologist that is not specialty trained in anesthesia is able to provide S/A safely in a freestanding facility.

Abstract: Increasing the creation of arteriovenous fistulas in the maintenance of hemodialysis patients is of great importance to the nephrology community. The creation of the brachial artery-basilic vein fistula is an important option in patients with unsuccessful or failing forearm accesses for hemodialysis. The aim of this study is to review reported outcomes of brachial artery-basilic vein fistulas regarding patency and primary failure rates in comparison with other types of fistulas and grafts in the published literature. We have also described the variations in the surgical technique during creation and the potential influence on outcomes. Based on our review of the literature, the rate of primary failure is approximately 15-20% with a range of 0-40%. The mean 1-year primary patency rate is approximately 72% with a range of 23-90%, and the 2-year primary patency rate is approximately 62% with a range from 11% to 86%. The number of required interventions to maintain patency is lower with brachial artery-basilic vein fistula compared to arteriovenous grafts.

Abstract: Dialysis catheter-related bacteremia (CRB) can frequently be treated with systemic antibiotics, in conjunction with an antibiotic lock, in an attempt to salvage the catheter. It is unknown whether CRB associated with an exit-site infection can be treated with such an approach. We retrospectively queried a prospective, computerized vascular access database, and identified 1436 episodes of CRB, of which 64 cases had a concurrent exit site. The frequency of concurrent exit-site infection was 9.6% with Staphylococcus epidermidis, 6.1% with Staphylococcus aureus, and only 0.7% with Gram negative CRB (p < 0.001 for Staphylococcus vs. Gram negative rods). Five serious complications (four major sepses and one endocarditis) occurred in 24 patients with S. aureus infection, but none in 32 episodes of S. epidermidis infection (p = 0.01). Catheter survival was significantly shorter in patients with S. aureus infections. The median catheter survival (without infection or dysfunction) was 14 days with S. aureus vs. 30 days with S. epidermidis infection (p = 0.035). In conclusion, concurrent exit-site infection is seen most commonly in association with Staphylococcal CRB. When the infecting organism is S. epidermidis, attempted salvage with systemic antibiotics and an antibiotic lock is reasonable. However, prompt catheter removal is indicated when the pathogen is S. aureus.

Abstract: Children receiving chronic hemodialysis (HD) three times a week have many obstacles to overcome. Not only do they have to endure dietary restrictions, but they also need to take various medications on a daily basis, which contribute to anorexia. Children on such conventional dialysis programs often have poorly controlled blood pressure (which can lead to left ventricular hypertrophy and/or left ventricular dysfunction) and impaired statural growth. Therefore, the need for more frequent and/or intensive dialysis is recognized. Nevertheless despite limited center experience, daily dialysis is currently most often limited as a rescue treatment. When performed, daily intensified HD provides a modality for preserving cardiovascular health and promoting normal growth in children. Therefore, the time spent on chronic dialysis preserves their chances of the best possible outcome.

Abstract: Both the Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines and the European Best Practice Guidelines (EBPG) support the use of substantial doses of iron supplementation when iron overload cannot be confirmed. However, excessive iron reduces iron utilization and is involved in the generation of intracellular reactive oxygen species, which induce cell injury; the risk of subtle toxicity from iron excess exists. Unnecessary iron supplementation also accelerates hepcidin (HP) production. HP, via its effect on ferroportin 1 (FP-1), keeps intracellular iron from being carried even if the iron storage is adequate; it also decreases iron absorption from the intestine. The Japanese Society for Dialysis Therapy Guidelines propose that a minimal amount of iron should be given to chronic kidney disease patients with anemia and only in cases of evident iron deficiency. Japanese clinicians believe that the risk/benefit ratio for iron supplementation is higher than that accepted in Western countries. When erythropoiesis-stimulating agent hyporesponsiveness exists, we should consider conditions other than iron deficiency and treat these conditions to improve iron utilization.

Abstract: The underlying inflammatory component of chronic kidney disease may predispose blood vessels to intimal hyperplasia (IH), which is the primary cause of dialysis access failure. We hypothesize that vascular pathology and markers of IH formation are antecedent to arteriovenous (AV) fistula creation. Blood, cephalic, and basilic vein segments were collected from predialysis chronic kidney disease (CKD) patients with no previous AV access and patients with end-stage renal disease (ESRD). Immunohistochemistry was performed with antibodies against mast cell chymase, transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6), which cause IH. Plasma chymase was measured by ELISA. IH was present in 91% of CKD and 75% of ESRD vein segments. Chymase was abundant in vessels with IH, with the greatest expression in intima and medial layers, and virtually absent in the controls. Chymase colocalized with TGF-β1 and IL-6. Plasma chymase concentration was elevated up to 33-fold in patients with CKD versus controls and was associated with increased chymase in vessels with IH. We show that chymase expression in vessels with IH corresponds with plasma chymase concentrations. As chymase inhibition attenuates IH in animal models, and we find chymase is highly expressed in IH lesions of patients with CKD and ESRD, we speculate that chymase inhibition could have therapeutic value in humans.

Abstract: Hemodialysis (HD) is often used as an example of the most expensive chronic medical intervention that society will pay for on an ongoing basis. More intensive forms of HD have been associated with improved clinical outcomes, but concerns have been raised regarding the possibility of increased costs. We review recent Canadian studies examining the costs and cost utility of intensive HD, with a focus on comparisons with conventional in-center hemodialysis (IHD). The costs of starting a new home nocturnal hemodialysis (HNHD) program in British Columbia was estimated to be about $510,000 for the first year of the program, including the training of the first 53 patients, or about $18,830 per patient. A study by Lee et al. found the costs of home HD to be substantially less than IHD ($93,976 vs. $54,936, p < 0.001). A study by Kroeker et al. found that the lowest costs were seen with home short daily HD ($82,522), compared with $89,154 for IHD, and $91,218 for HNHD. Two studies by McFarlane et al. found that total costs were lower for those receiving HNHD (IHD $87,172 vs. HNHD $71,313), and that HNHD was associated with a superior cost-utility ratio (CAN$ 2011, HNHD $84,430/quality-adjusted life year [QALY] vs. IHD $148,722/QALY, incremental cost-effectiveness ratio: -$54,281, p < 0.05). While consistent findings of lower staffing and overhead costs for home HD, and higher consumable costs for frequent dialysis are probably reliable, findings of lower medication and hospital admission costs seen with intensive HD will need confirmation in randomized studies. Modifications to conventional dialysis funding are needed to accommodate for the additional costs of supplies and technology needed to support intensive modalities.

Abstract: Non-maturation is a common problem in patients receiving an arteriovenous fistula The first vascular access choice is a distal radiocephalic fistula (dRCF) at the wrist Patients with a failed dRCF or with vessels unsuitable for dRCF, the recommendation is to place a brachiocephalic fistula in the upper arm Proximal forearm radiocephalic fistulas (pRCF) are created infrequently, but may permit a second forearm fistula before proceeding to the upper arm The goal of the present study was to compare the outcomes of them We retrospectively analyzed a computerized access database to compare the outcomes of 19 RCF and 39 dRCF placed during a 6-month period The baseline characteristics were similar, except those with a pRCF were more likely to have previous access and be male Primary failure (non-maturation) was lower for pRCF than dRCF (32 vs 59%, p = 005); and excluding secondary failures, cumulative fistula survival was similar (92 vs 86% at 1 year and 74 vs 76% at 2 years, p = 056) pRCF may be an attractive alternative to a brachiocephalic fistula in patients who cannot receive a dRCF pRCF has a lower non-maturation rate than that of a dRCF, and a comparable cumulative survival once it is used successfully for dialysis