Carolyn van Eps

Randomized, Controlled Trial of Topical Exit-Site Application of Honey (Medihoney) versus Mupirocin for the Prevention of Catheter-Associated Infections in Hemodialysis Patients

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Intradermal versus intramuscular hepatitis B vaccination in hemodialysis patients: a prospective open-label randomized controlled trial in nonresponders to primary vaccination.

BACKGROUND Primary hepatitis B virus (HBV) vaccination through the intramuscular (IM) route is less efficacious in dialysis patients than in the general population. Previous studies suggest improved seroconversion with intradermal (ID) vaccination. STUDY DESIGN Prospective open-label randomized controlled trial. SETTING & PARTICIPANTS Hemodialysis patients nonresponsive to primary HBV vaccination. INTERVENTION Revaccination with either ID (10 microg of vaccine every week for 8 weeks) [DOSAGE ERROR CORRECTED] or IM (40 microg of vaccine at weeks 1 and 8) HBV vaccine . OUTCOMES PRIMARY OUTCOME proportion of patients achieving HBV surface antibody (anti-HBs) titer of 10 IU/L or greater within 2 months of vaccination course. SECONDARY OUTCOMES time to seroconversion, predictors of seroconversion, peak antibody titer, duration of seroprotection, and safety and tolerability of vaccine. MEASUREMENTS Anti-HBs titer to 24 months. RESULTS 59 patients were analyzed. Seroconversion rates were 79% ID versus 40% IM (P = 0.002). The unadjusted odds ratio for seroconversion for ID versus IM was 5.5 (95% confidence interval [CI], 1.6 to 18.4) and increased with adjustment for baseline differences. The only factor predictive of seroconversion was the ID vaccination route. The geometric mean peak antibody titer was significantly greater in the ID versus IM group: 239 IU/L (95% CI, 131 to 434) versus 78 IU/L (95% CI, 36 to 168; P < 0.001). There was a trend toward longer duration of seroprotection with ID vaccination. ID vaccine was safe and well tolerated. LIMITATIONS Inability to distinguish whether the mechanism of the greater efficacy of ID vaccination was the cumulative effect of multiple injections or route of administration; use of anti-HBs as a surrogate marker of protection; lack of evidence of long-term protection. CONCLUSIONS Significantly greater seroconversion rates and peak antibody titers can be achieved with ID compared with IM vaccination in hemodialysis patients nonresponsive to primary vaccination. ID vaccination should become the standard of care in this setting.

The impact of extended-hours home hemodialysis and buttonhole cannulation technique on hospitalization rates for septic events related to dialysis access

Few studies adequately document adverse events in patients receiving long, slow, and overnight hemodialysis (NHD). Concerns about high rates of dialysis access complications have been raised. This is an observational cohort study comparing hospital admission rates for vascular access complications between alternate nightly NHD (n=63) and conventional hemodialysis (n=172) patients established on chronic hemodialysis for at least 3 months. Overall, hospital admission rates and hospital admission rates for cardiac and all infective events are also reported. The NHD cohort was younger and less likely to be female, diabetic, or have ischemic heart disease than the conventional hemodialysis cohort. When NHD and buttonhole cannulation technique were used simultaneously, there was a demonstrated increased risk of septic dialysis access events: incidence rate ratio 3.0 (95% confidence interval 1.04–8.66) (P=0.04). The majority of blood culture isolates in NHD patients were gram‐positive organisms, particularly Staphylococcus aureus. Alternate nightly NHD did not significantly change total hospital admissions or hospital admissions for indications other than dialysis access complications, compared with conventional hemodialysis. Our data suggest that buttonhole cannulation technique should be used with caution in patients performing extended‐hours hemodialysis as this combination appears to increase the risk of septic access complications. Randomized‐controlled trials are needed to confirm these findings.

Outcomes of Extended-Hours Hemodialysis Performed Predominantly at Home

BACKGROUND Recent evidence suggests that increased frequency and/or duration of dialysis are associated with improved outcomes. We aimed to describe the outcomes associated with patients starting extended-hours hemodialysis and assess for risk factors for these outcomes. STUDY DESIGN Case series. SETTING & PARTICIPANTS Patients were from 6 Australian centers offering extended-hours hemodialysis. Cases were patients who started treatment for 24 hours per week or longer at any time. OUTCOMES All-cause mortality, technique failure (withdrawal from extended-hours hemodialysis therapy), and access-related events. MEASUREMENTS Baseline patient characteristics (sex, primary cause of end-stage kidney disease, age, ethnicity, diabetes, and cannulation technique), presence of a vascular access-related event, and dialysis frequency. RESULTS 286 patients receiving extended-hours hemodialysis were identified, most of whom performed home (96%) or nocturnal (77%) hemodialysis. Most patients performed alternate-daily dialysis (52%). Patient survival rates using an intention-to-treat approach at 1, 3, and 5 years were 98%, 92%, and 83%, respectively. Of 24 deaths overall, cardiac death (n = 7) and sepsis (n = 5) were the leading causes. Technique survival rates at 1, 3, and 5 years were 90%, 77%, and 68%, respectively. Access event-free rates at the same times were 80%, 68%, and 61%, respectively. Access events significantly predicted death (HR, 2.85; 95% CI, 1.14-7.15) and technique failure (HR, 3.76; 95% CI, 1.93-7.35). Patients with glomerulonephritis had a reduced risk of technique failure (HR, 0.31; 95% CI, 0.14-0.69). Higher dialysis frequency was associated with elevated risk of developing an access event (HR per dialysis session, 1.56; 95% CI, 1.03-2.36). LIMITATIONS Selection bias, lack of a comparator group. CONCLUSIONS Extended-hours hemodialysis is associated with excellent survival rates and is an effective treatment option for a select group of patients. The major treatment-associated adverse events were related to complications of vascular access, particularly infection. The risk of developing vascular access complications may be increased in extended-hours hemodialysis, which may negatively affect long-term outcomes.

Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice?

BackgroundAluminium-containing phosphate binders have long been used for treatment of hyperphosphatemia in dialysis patients. Their safety became controversial in the early 1980s after reports of aluminium related neurological and bone disease began to appear. Available historical evidence however, suggests that neurological toxicity may have primarily been caused by excessive exposure to aluminium in dialysis fluid, rather than aluminium-containing oral phosphate binders. Limited evidence suggests that aluminium bone disease may also be on the decline in the era of aluminium removal from dialysis fluid, even with continued use of aluminium binders.DiscussionThe K/DOQI and KDIGO guidelines both suggest avoiding aluminium-containing binders. These guidelines will tend to promote the use of the newer, more expensive binders (lanthanum, sevelamer), which have limited evidence for benefit and, like aluminium, limited long-term safety data. Treating hyperphosphatemia in dialysis patients continues to represent a major challenge, and there is a large body of evidence linking serum phosphate concentrations with mortality. Most nephrologists agree that phosphate binders have the potential to meaningfully reduce mortality in dialysis patients. Aluminium is one of the cheapest, most effective and well tolerated of the class, however there are no prospective or randomised trials examining the efficacy and safety of aluminium as a binder. Aluminium continues to be used as a binder in Australia as well as some other countries, despite concern about the potential for toxicity. There are some data from selected case series that aluminium bone disease may be declining in the era of reduced aluminium content in dialysis fluid, due to rigorous water testing.SummaryThis paper seeks to revisit the contemporary evidence for the safety record of aluminium-containing binders in dialysis patients. It puts their use into the context of the newer, more expensive binders and increasing concerns about the risks of calcium binders, which continue to be widely used. The paper seeks to answer whether the continued use of aluminium is justifiable in the absence of prospective data establishing its safety, and we call for prospective trials to be conducted comparing the available binders both in terms of efficacy and safety.

Mineral metabolism, bone histomorphometry and vascular calcification in alternate night nocturnal haemodialysis

Background:  Poor control of bone mineral metabolism (BMM) is associated with renal osteodystrophy and mortality in dialysis‐dependent patients. The authors explored the efficacy of alternate nightly home haemodialysis (ANHHD) in controlling BMM parameters and its effects on bone mineral density and histomorphometry.

Changes in serum prolactin, sex hormones and thyroid function with alternate nightly nocturnal home haemodialysis

Aim:  Uraemia is associated with hyperprolactinaemia, low total (TT) and free (FT) serum testosterone, high luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) and, in women, anovulatory cycles and premature menopause. We hypothesize that extended hours haemodialysis may improve these derangements.

Quality of life and alternate nightly nocturnal home hemodialysis

Hemodialysis has been associated with reduced quality of life (QOL). Small cohort studies of quotidian hemodialysis regimens suggest general QOL and dialysis‐related symptoms may improve compared with conventional regimens. An observational cohort study was conducted on 63 patients (age 51.7 ± 12.9 years; 79.4% male; 33.3% diabetes; duration of renal replacement therapy 1.9 [0.7–6.4] years) converted from conventional home hemodialysis (3–5 sessions weekly, 3–6 h/session) to home nocturnal home hemodialysis (NHD) (3–5 sessions weekly, 6–10 h/session). Kidney Disease Quality of Life (KDQOL) and Assessment of Quality of Life instruments and 6‐minute–walk tests were applied at baseline and 6 months. Baseline and 6 month surveys were returned by 70% of patients. On KDQOL, significant improvements in general health (P=0.02) and overall health ratings (P=0.0008), physical function (P=0.003), physical role (P=0.018), and energy and fatigue (P=0.027) were documented. There was a trend toward improvement in burden of kidney disease (P=0.05) and emotional role (P=0.066). There was a significant improvement in distance covered in the 6‐minute–walk test from 513 m (420.5–576.4) to 536.5 m (459–609), P=0.007. On Assessment of Quality of Life, there was a trend toward improvement in overall utility score from 0.65 (0.39–0.81) to 0.73 (0.46–0.86), P=0.096. After 86.2 patient‐years of observation, 23 patients have discontinued NHD (12 transplanted, 5 deceased, 4 psychosocial problems, 1 dialysis access problem, 1 medically unsuitable). Nocturnal home hemodialysis is a sustainable therapy. In addition to improving general QOL, alternate nightly NHD can significantly improve physical functioning as measured by KDQOL and 6‐minute–walk tests.

A randomized controlled trial of intravenous or oral iron for posttransplant anemia in kidney transplantation

Background. Anemia after kidney transplantation has been associated with poor transplant outcomes. We hypothesized that intravenous (IV) iron may more rapidly correct anemia than oral (PO) iron. Methods. One hundred four kidney transplant recipients were prospectively randomized to IV iron polymaltose (500 mg single dose) or PO ferrous sulfate (210 mg elemental iron daily, continuously). The primary outcome was time to resolution of anemia, defined as hemoglobin more than or equal to 11 g/dL. Secondary outcomes included infections, blood transfusions, gastrointestinal side-effects, and acute rejection. Results. There was no significant difference in the primary outcome comparing IV with PO iron (hazards ratio 1.22; 95% confidence interval 0.82–1.83; P=0.32). The median time to resolution of anemia was 12 days in the IV group versus 21 days in the PO group. There were no differences in infections (20% vs. 24%, P=0.62), acute rejection (8% vs. 6%, P=0.68), blood transfusions (10% vs. 18%, P=0.24), and severe gastrointestinal side-effects (6% vs. 12%, P=0.29) between the IV iron and the PO iron groups. Conclusions. We conclude that a single dose of IV iron did not result in more rapid resolution of anemia compared with PO iron. Both IV and PO iron are safe and effective in the management of posttransplant anemia.

A randomized controlled trial of oral heme iron polypeptide versus oral iron supplementation for the treatment of anaemia in peritoneal dialysis patients: HEMATOCRIT trial

BACKGROUND Preliminary clinical evidence suggests that heme iron polypeptide (HIP) might represent a promising, novel oral iron supplementation strategy in chronic kidney disease. The aim of this multi-centre randomized controlled trial was to determine the ability of HIP administration to augment iron stores in darbepoetin (DPO)-treated patients compared with conventional oral iron supplementation. METHODS Adult peritoneal dialysis (PD) patients treated with DPO were randomized 1:1 to receive two capsules daily of either HIP or ferrous sulphate per os for 6 months. The primary outcome measure was transferrin saturation (TSAT). Secondary outcomes comprised serum ferritin, haemoglobin, DPO dose and responsiveness, and adverse events. RESULTS Sixty-two patients were randomized to HIP (n = 32) or ferrous sulphate (n = 30). On intention-to-treat analysis, the median (inter-quartile range) TSAT was 22% (16-29) in the HIP group compared with 20% (17-26) in controls (P = 0.65). HIP treatment was not significantly associated with TSAT at 6 months on multivariable analysis (P = 0.95). Similar results were found on per-protocol analysis and subgroup analysis in iron-deficient patients. Serum ferritin levels at 6 months were significantly lower in the HIP group (P = 0.003), while the cost of HIP was 7-fold higher than that of ferrous sulphate. No other differences in secondary outcomes were observed. CONCLUSIONS HIP showed no clear safety or efficacy benefit in PD patients compared with conventional oral iron supplements. The reduction in serum ferritin levels and high costs associated with HIP therapy suggest that this agent is unlikely to have a significant role in iron supplementation in PD patients.