BACKGROUND:

Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF.

METHODS:

In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h.

RESULTS:

All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed.

CONCLUSIONS:

Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Willem Kolff (1911-2009), son of a physician, studied medicine in Leiden and specialised in internal medicine in Groningen. It was there that he started attempts to apply the phenomenon of dialysis in patients suffering from renal failure. He built the first prototypes of dialysis machines after his appointment as an internist in the municipal hospital in Kampen, during the Second World War. Indeed, in the first 15 patients he managed to decrease urea levels, resulting in temporary clinical improvement, but eventually they all died. It was not until after the war that dialysis helped a patient survive an episode of acute glomerulonephritis. After 1950 he continued his work on artificial organs in the United States (first in Cleveland and later, after 1967, in Salt Lake City). Although most of his work from then on revolved around the development of an artificial heart, he also contributed to the design of a compact, disposable apparatus for dialysis, the 'twin coil'. Haemodialysis also became feasible for patients with chronic renal failure after the 'Scribner shunt' (1960) provided easy access to the circulation. Peritoneal dialysis is another option. Excess mortality, mainly from cardiovascular disease, is still a largely unsolved problem.

Despite all the progress achieved since Scribner first introduced the arteriovenous (AV) shunt in 1960 and Cimino and Brescia introduced the native AV fistula in 1962, we have continued to face a conundrum in vascular access for dialysis, in that dialysis vascular access is at the same time both the 'lifeline' and the 'Achilles' heel' of haemodialysis. Indeed, findings from a multitude of published articles in this area, unfortunately mainly observational studies, reflect both our frustration and our limited knowledge in this area. Despite improved understanding of the pathophysiology of stenosis and thrombosis of the vascular access, we have unfortunately not been very successful in translating these advances into either improved therapies or a superior process of care. As a result, we continue to face an epidemic of arteriovenous fistula (AVF) maturation failure, a proliferation of relatively ineffective interventions such as angioplasty and stent placement, an extremely high incidence of catheter use, and more doubts rather than guidance with regard to the role (or lack thereof) of surveillance. An important reason for these problems is the lack of focused translational research and robust randomized prospective studies in this area. In this Review, we will address some of these critical issues, with a special emphasis on identifying the best process of care pathways that could reduce morbidity and mortality. We also discuss the potential use of novel therapies to reduce dialysis vascular access dysfunction.

Chronic kidney disease currently affects one in nine Americans and over 500,000 have progressed to failure requiring kidney replacement therapy, with nearly 45% being women. Clinical Practice Guidelines have been developed in an effort to synthesize the latest literature, particularly randomized controlled trials, to assist clinical decision making. Women have different levels of kidney function than men at the same level of serum creatinine and may also lose kidney function over time more slowly than men. Although the arteriovenous fistulae have long been recognized as the preferred access for hemodialysis, women are less likely to initiate dialysis with an arteriovenous fistula in place. In addition, the female sex is regarded as a risk factor for access failure as well for complications such as steal. This article reviews treatment of women with chronic kidney disease, focusing on the difficulties they are perceived to have with dialysis access.

Implantation of prosthetic vascular grafts is sometimes necessary to create vascular access as AV conduits for maintenance haemodialysis. Though more common in the western world, it is now also becoming an important option in our country. Here we summarise our experience with the procedure from 2001 to 2011. The technical configuration which seems to work better in India is different from what is commonly performed in the west. After a short review of the relevant basic sciences, our results are discussed and showed 95% one year graft patency. Conclusions drawn are objective and stresses on the need to increase awareness amongst all doctors about the importance of preserving forearm veins in patients with chronic kidney disease.

A 53-year-old woman was admitted to our hospital due to abdominal pain, diarrhea, and shunt occlusion caused by dehydration. She had undergone hemodialysis due to diabetic nephropathy over a ten-year period. She was hospitalized again with fever and a persistent high serum CRP level. We started antibiotic administration using cefotiam hexetil hydrochloride because of ascites and peritoneum thickening observed by abdominal computed tomography. Although her symptoms, such as abdominal pain and diarrhea, improved after the administration of antibiotics, the ascites and the peritoneum thickening did not improve. On the fourth hospital day, we attempted ascites aspiration to investigate the etiology of the peritonitis. Cytological examination suggested tuberculous peritonitis because of predominant macrophage cell proliferation, a high level of ADA concentration, and a high level of CA125 of ascites. Although QuantiFERON-tuberculosis (QFT) and the Gaffky scale were negative, we started multidrug therapy (isoniazid + rifampicin + pyrazinamide + ethambutol) on the 20th hospital day. She was finally diagnosed as mycobacterium tuberculous peritonitis based on biopsy of the tissue of the ileum and the results of colonoscopy. Administration of antituberculosis chemotherapy improved abdominal fullness and ascites and the patient was discharged on the 97th hospital day. Moreover Kuno et al. reported that serum soluble interleukin-2 receptor(sIL-2R) and CA-125 levels can be used to monitor the response to anti-tuberculosis treatment. In this case, we use these markers to monitor the response to treatment. We experienced a case of tuberculous peritonitis undergoing hemodialysis. Tuberculosis should be suspected when patients undergoing dialysis have long-term fever of unknown etiology. There are many reports stating that the sensitivity and specificity of QuantiFERON-tuberculosis (QFT) and sputum culture are low in latent tuberculosis infection of dialysis patients. Accordingly it is necessary to diagnose mycobacterium tuberculous peritonitis comprehensively by the clinical symptoms and image analysis.

Clinical practice guidelines recommend an arteriovenous fistula as the preferred vascular access for hemodialysis, but quantitative associations between vascular access type and various clinical outcomes remain controversial. We performed a systematic review of cohort studies to evaluate the associations between type of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) and risk for death, infection, and major cardiovascular events. We searched MEDLINE, EMBASE, and article reference lists and extracted data describing study design, participants, vascular access type, clinical outcomes, and risk for bias. We identified 3965 citations, of which 67 (62 cohort studies comprising 586,337 participants) met our inclusion criteria. In a random effects meta-analysis, compared with persons with fistulas, those individuals using catheters had higher risks for all-cause mortality (risk ratio=1.53, 95% CI=1.41-1.67), fatal infections (2.12, 1.79-2.52), and cardiovascular events (1.38, 1.24-1.54). Similarly, compared with persons with grafts, those individuals using catheters had higher risks for mortality (1.38, 1.25-1.52), fatal infections (1.49, 1.15-1.93), and cardiovascular events (1.26, 1.11-1.43). Compared with persons with fistulas, those individuals with grafts had increased all-cause mortality (1.18, 1.09-1.27) and fatal infection (1.36, 1.17-1.58), but we did not detect a difference in the risk for cardiovascular events (1.07, 0.95-1.21). The risk for bias, especially selection bias, was high. In conclusion, persons using catheters for hemodialysis seem to have the highest risks for death, infections, and cardiovascular events compared with other vascular access types, and patients with usable fistulas have the lowest risk.

Initiatives to increase arteriovenous fistula (AVF) use are based on studies that show that AVFs require fewer interventions and have better patency than arteriovenous grafts (AVGs). Because patients who receive AVFs typically have more favorable vascular anatomy and are referred earlier for access placement than those who receive AVGs, the advantages of AVF might be overestimated. We compared outcomes for AVFs and AVGs in patients with equivalent vascular anatomy who were on dialysis via catheter at the time of vascular access placement.The study included patients who underwent placement of a first-time AVF or AVG between 2006 and 2009, who were on dialysis via catheter at the time of access placement, and who had favorable arterial and venous (>3 mm) anatomy. Outcomes for AVF and AVG were compared.Eighty-nine AVF and 59 AVG patients met study inclusion criteria. Similar secondary patency was achieved by AVG and AVF at 12 (72% vs 71%) and 24 months (57% vs 62%), respectively (p = 0.96). The number of interventions required to maintain patency for AVF (n = 1; range 0 to 10) and AVG (n = 1; range 0 to 11) were not different (p = 0.36). However, the number of catheter days to first access use was more than doubled in the AVF group (median 81 days) compared with the AVG group (median 38 days; p < 0.001).For patients who are receiving dialysis via catheter at the time of access placement, the maturation time, risk of nonmaturation, and interventions required to achieve a functional AVF can negate its benefits over AVG. A fistula first approach might not always apply to patients who are already on dialysis when referred for chronic access placement.

Frequent hemodialysis requires using the vascular access more often than with conventional hemodialysis, but whether this increases the risk for access-related complications is unknown. In two separate trials, we randomly assigned 245 patients to receive in-center daily hemodialysis (6 days per week) or conventional hemodialysis (3 days per week) and 87 patients to receive home nocturnal hemodialysis (6 nights per week) or conventional hemodialysis, for 12 months. The primary vascular access outcome was time to first access event (repair, loss, or access-related hospitalization). Secondary outcomes were time to all repairs and time to all losses. In the Daily Trial, 77 (31%) of 245 patients had a primary outcome event: 33 repairs and 15 losses in the daily group and 17 repairs, 11 losses, and 1 hospitalization in the conventional group. Overall, the risk for a first access event was 76% higher with daily hemodialysis than with conventional hemodialysis (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.11-2.79; P=0.017); among the 198 patients with an arteriovenous (AV) access at randomization, the risk was 90% higher with daily hemodialysis (HR, 1.90; 95% CI, 1.11-3.25; P=0.02). Daily hemodialysis patients had significantly more total AV access repairs than conventional hemodialysis patients (P=0.011), with 55% of all repairs involving thrombectomy or surgical revision. Losses of AV access did not differ between groups (P=0.58). We observed similar trends in the Nocturnal Trial, although the results were not statistically significant. In conclusion, frequent hemodialysis increases the risk of vascular access complications. The nature of the AV access repairs suggests that this risk likely results from increased hemodialysis frequency rather than heightened surveillance.

Vascular access by dialysis graft or fistula is of major importance for hemodialysis treatment. Vascular access occlusion is one main reason for hospitalization of patients on hemodialysis. Thrombophilic risk factors are discussed as one cause for occlusion. The aim of this study was to determine if the presence of thrombophilic factors is associated with a reduced survival rate of vascular dialysis access.The following thrombophilic parameters were measured in every hemodialysis patient from five outpatient dialysis centers in Berlin: antithrombin, protein C, protein S, prothrombin mutation (G20210A), factor V mutation (G1691A), lupus anticoagulant, anticardiolipin antibodies, factor VIII, plasminogen activator inhibitor, homocysteine and lipoprotein(a). Vascular access characteristics such as vascular access material (PTFE graft or native fistula) and location were also recorded. Each patient's medical history was documented.199 patients with a total of 499 vascular accesses in the past (311 native fistulas (62.3 %) and 188 PTFE grafts (33.7 %)) were included in this study. The type of vascular access played an important role, with mean survival times of 34.2 months for native fistulas versus 9.5 months for grafts. There was at least one thrombophilic risk factor present in 69.8 % of the patients. In the univariate analysis thrombophilia had a significant influence on vascular access survival. The effect persisted throughout the multivariate analysis. Multivariate Cox analysis showed that the presence of thrombophilic factors was associated with a 43 % (mild) to 105 % (severe thrombophilia) increased risk of occlusion of the vascular access, corresponding to a 45 % to 68 % reduction of native access survival time. The influence of thrombophilia was evident in fistulas as well as in PTFE grafts.Thrombophilia plays a role in vascular accesses survival in patients on hemodialysis. In hemodialysis patients with recurrent occlusions of vascular access thrombophilia testing should be performed.