Impact of deceased donor with acute kidney injury on subsequent kidney transplant outcomes-an ANZDATA registry analysis.

BACKGROUND: The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature. MATERIAL AND METHODS: This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection. RESULTS: The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99-1.26), death-censored graft failure (HR 1.09, 95% CI 0.92-1.28), death (HR 1.15, 95% CI 0.98-1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91-1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92-2.68). CONCLUSION: Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

Multicenter registry analysis comparing survival on home hemodialysis and kidney transplant recipients in Australia and New Zealand.

BACKGROUND: In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients. METHODS: The Australia and New Zealand Dialysis and Transplant Registry was used to include incident HHD patients on Day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan-Meier product-limit method comparing HHD patients with subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome. RESULTS: The study compared 1411 HHD patients with 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared with HHD patients [LD adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.46-0.71; SCD HR = 0.65 95% CI 0.52-0.79], the risk of mortality was comparable between ECD recipients and HHD patients (HR = 0.90, 95% CI 0.73-1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared with HHD patients. CONCLUSIONS: This large registry study showed that kidney transplant offers a survival benefit compared with HHD but that this advantage is not significant for ECD recipients.

Variability and trends over time and across centres in haemodialysis weekly duration in Australia and New Zealand.

AIM: Haemodialysis treatment prescription varies widely internationally. This study explored patient- and centre-level characteristics associated with weekly haemodialysis hours. METHODS: Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry data were analysed. Characteristics associated with weekly duration were evaluated using mixed-effects linear regression models with patient- and centre-level covariates as fixed effects, and dialysis centre and state as random effects using the 2017 prevalent in-centre haemodialysis (ICHD) and home haemodialysis (HHD) cohorts. Evaluation of patterns of weekly duration over time analysed the 2000 to 2017 incident ICHD and HHD cohorts. RESULTS: Overall, 12 494 ICHD and 1493 HHD prevalent patients in 2017 were included. Median weekly treatment duration was 13.5 (interquartile range [IQR] 12-15) hours for ICHD and 16 (IQR 15-20) hours for HHD. Male sex, younger age, higher body mass index, arteriovenous fistula/graft use, Aboriginal and Torres Strait Islander ethnicity and longer dialysis vintage were associated with longer weekly duration for both ICHD and HHD. No centre characteristics were associated with duration. Variability in duration across centres was very limited in ICHD compared with HHD, with variation in HHD being associated with state. Duration did not vary significantly over time for ICHD, whereas longer weekly HHD treatments were reported between 2006 and 2012 compared with before and after this period. CONCLUSION: This study in the Australian and New Zealand haemodialysis population showed that weekly duration was primarily associated with patient characteristics. No centre effect was demonstrated. Practice patterns seemed to differ across states/countries, with more variability in HHD than ICHD.

Rate of decline in residual kidney function pre and post peritoneal dialysis initiation: A post hoc analysis of the IDEAL study.

BACKGROUND: Residual kidney function (RKF) is associated with improved survival and quality of life in dialysis patients. Previous studies have suggested that initiation of peritoneal dialysis (PD) may slow RKF decline compared to the pre-dialysis period. We sought to evaluate the association between PD initiation and RKF decline in the Initiating Dialysis Early And Late (IDEAL) trial. METHODS: In this post hoc analysis of the IDEAL randomized controlled trial, PD participants were included if results from 24-hour urine collections had been recorded within 30 days of dialysis initiation, and at least one value pre- and one value post-dialysis commencement were available. The primary outcome was slope of RKF decline, calculated as mean of urinary creatinine and urea clearances. Secondary outcomes included slope of urine volume decline and time from PD initiation to anuria. RESULTS: The study included 151 participants (79 early start, 72 late start). The slope of RKF decline was slower after PD initiation (-2.69±0.18mL/min/1.73m2/yr) compared to before PD (-4.09±0.33mL/min/1.73m2/yr; change in slope +1.19 mL/min/1.73m2/yr, 95%CI 0.48-1.90, p<0.001). In contrast, urine volume decline was faster after PD commencement (-0.74±0.05 L/yr) compared to beforehand (-0.57±0.06L/yr; change in slope -0.18L/yr, 95%CI -0.34--0.01, p = 0.04). No differences were observed between the early- and late-start groups with respect to RKF decline, urine volume decline or time to anuria. CONCLUSIONS: Initiation of PD was associated with a slower decline of RKF compared to the pre-dialysis period.

Effect of patient- and center-level characteristics on uptake of home dialysis in Australia and New Zealand: a multicenter registry analysis.

BACKGROUND: Home-based dialysis therapies, home hemodialysis (HHD) and peritoneal dialysis (PD) are underutilized in many countries and significant variation in the uptake of home dialysis exists across dialysis centers. This study aimed to evaluate the patient- and center-level characteristics associated with uptake of home dialysis. METHODS: The Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry was used to include incident dialysis patients in Australia and New Zealand from 1997 to 2017. Uptake of home dialysis was defined as any HHD or PD treatment reported to ANZDATA within 6 months of dialysis initiation. Characteristics associated with home dialysis uptake were evaluated using mixed effects logistic regression models with patient- and center-level covariates, era as a fixed effect and dialysis center as a random effect. RESULTS: Overall, 54 773 patients were included. Uptake of home-based dialysis was reported in 24 399 (45%) patients but varied between 0 and 87% across the 76 centers. Patient-level factors associated with lower uptake included male sex, ethnicity (particularly indigenous peoples), older age, presence of comorbidities, late referral to a nephrology service, remote residence and obesity. Center-level predictors of lower uptake included small center size, smaller proportion of patients with permanent access at dialysis initiation and lower weekly facility hemodialysis hours. The variation in odds of home dialysis uptake across centers increased by 3% after adjusting for the era and patient-level characteristics but decreased by 24% after adjusting for center-level characteristics. CONCLUSION: Center-specific factors are associated with the variation in uptake of home dialysis across centers in Australia and New Zealand.

Kidney Health Australia - Caring for Australasians with Renal Impairment guideline recommendations for infection control for haemodialysis units.

AIM: There is no national consensus on infection control in haemodialysis units in Australia and New Zealand. The primary aim of this guideline was to provide recommendations on screening for blood-borne viruses and multi-resistant organisms for dialysis units based on the available evidence. METHODS: The Kidney Health Australia Caring for Australasians with Renal Impairment guidelines, overall approach to guideline development follows the GRADE framework. A facilitated workshop was conducted to ensure that patient and caregiver concerns were considered. The evidence from relevant medical databases on the impact of screening on detection and transmission rates, hospitalization, mortality and psychosocial care, was reviewed and critically appraised. The guideline group made recommendations from the evidence available. RESULTS: The main guideline recommendations are: Dialysis units adopt a comprehensive approach that encompasses standard infection control precautions. Conduct routine surveillance for key blood-borne viruses and methicillin-resistant Staphylococcus aureus. Conduct routine surveillance of individual levels of protection against hepatitis B for patients on haemodialysis. Use dedicated dialysis machines for HBV-infected patients. The evidence in totality was not found to support routine surveillance of vancomycin-resistant Enterococci . Enhanced surveillance in light of the local risk of transmittable infectious agents should be considered by dialysis units. Very few studies have reported on the potential adverse effects of screening and associated practices. CONCLUSIONS: Future research should focus on the potential benefits and adverse effects of screening and associated practices on clinical outcomes including infections prevented and health service delivery, and psychosocial domains for patients. Given the results of trials in the critical setting, the effectiveness of methicillin-resistant Staphylococcus aureus decolonization in people receiving dialysis therapy warrants further research.

Identifying and integrating patient and caregiver perspectives for clinical practice guidelines on the screening and management of infectious microorganisms in hemodialysis units.

INTRODUCTION: The integration of patient and caregiver input into guideline development can help to ensure that clinical care addresses patient expectations, priorities, and needs. We aimed to identify topics and outcomes salient to patients and caregivers for inclusion in the Kidney Health Australia Caring for Australasians with Renal Impairment (KHA-CARI) clinical practice guideline on the screening and management of infectious microorganisms in hemodialysis units. METHODS: A facilitated workshop was conducted with 11 participants (patients [n = 8], caregivers [n = 3]). Participants identified and discussed potential topics for inclusion in the guidelines, which were compared to those developed by the guideline working group. The workshop transcript was thematically analyzed to identify and describe the reasons underpinning their priorities. FINDINGS: Patients and caregivers identified a range of topics already covered by the scope of the proposed guidelines and also suggested additional topics: privacy and confidentiality, psychosocial care during/after disease notification, quality of transportation, psychosocial treatment of patients in isolation, patient/caregiver education and engagement, and patient advocacy. Five themes characterized discussion and underpinned their choices: shock and vulnerability, burden of isolation, fear of infection, respect for privacy and confidentiality, and confusion over procedural inconsistencies. DISCUSSION: Patients and caregivers emphasized the need for guidelines to address patient education and engagement, and the psychosocial implications of communication and provision of care in the context of infectious microorganisms in hemodialysis units. Integrating patient and caregiver perspectives can help to improve the relevance of guidelines to enhance quality of care, patient experiences, and health and psychosocial outcomes.

Prescriptions for home hemodialysis.

Prescribing a regimen that provides "optimal dialysis" to patients who wish to dialyze at home is of major importance, yet there is substantial variation in how home hemodialysis (HD) is prescribed. Geographic location, patient health status and clinical goals, and patient lifestyle and preferences all influence the selection of a prescription for a particular patient-there is no single prescription that provides optimal therapy for all patients, and careful weighing of potential benefit and burden is required for long-term success. This article describes how home HD prescribing patterns have changed over time and provides examples of commonly used home HD prescriptions. In addition, associated clinical outcomes and adequacy parameters as well as criteria for identifying which patients may benefit most from these diverse prescriptions are also presented.

Psychological factors associated with successful outcomes in home haemodialysis.

AIM: Performing haemodialysis therapy at home has been associated with improved survival for end-stage kidney disease patients and can generally be delivered at a lower cost to the healthcare system when compared with centre and satellite unit dialysis. However, only a minority of dialysis dependent end-stage kidney disease patients successfully sustain haemodialysis at home. Current practice for determining dialysis treatment modality and location takes into account medical suitability and social situation, but infrequently formally examines the contribution of psychological factors. This study explores demographic, health, and psychological factors that may predict patients' ability to sustain home haemodialysis. METHODS: One hundred and thirteen successful and unsuccessful home haemodialysis users were recruited to the study, and 55 responded to self-report measures. Demographic (age, gender, education level, carer support), health (comorbidities, diabetes, psychiatric condition) and psychological (locus of control beliefs, coping styles) information was used as predictor variables for the participants' time maintaining home therapy (Home Time). RESULTS: In a three-step regression, the model explained 32% of variance in Home Time. Coping styles significantly contributed 16% of the variance in Home Time after accounting for other variables. Adaptive Coping was significantly correlated with the length of time sustaining home therapy. CONCLUSION: Adaptive coping strategies are associated with improved ability to sustain home haemodialysis therapy. Evidence-based psychological approaches can help patients develop more adaptive coping strategies. More research is needed to assess whether instituting these psychological interventions will assist patients to adopt and sustain dialysis therapies which require increased patient self-management.

Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody-associated vasculitis has been associated with many drugs and it is a relatively rare side effect of the antihypertensive drug hydralazine. The diagnosis and management of patients who have anti-neutrophil cytoplasmic antibody-associated vasculitis may be challenging because of its relative infrequency, variability of clinical expression and changing nomenclature. The spectrum of anti-neutrophil cytoplasmic antibody-associated vasculitis is wide and can be fatal. This case documents a 62-year-old woman who presented with hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis with a puzzling cutaneous rash. CASE PRESENTATION: We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis in a 62-year-old Caucasian woman who presented with a vasculitic syndrome with a sore throat, mouth ulcers and otalgia after several months of constitutional symptoms. She then proceeded to develop a rash over her right lower limb. Clinically, the rash had features to suggest Sweet's syndrome, but also had some appearances consistent with embolic phenomena and did not have the appearance of palpable purpure usually associated with cutaneous vasculitis. Differential diagnoses were hydralazine-associated Sweet's syndrome, streptococcal-induced cutaneous eruption or an unrelated contact dermatitis. A midstream urine sample detected glomerular blood cells in the setting of anti-neutrophil cytoplasmic antibody-positive renal vasculitis and Streptococcus pyogenes bacteremia. A renal biopsy revealed a pauci-immune, focally necrotizing glomerulonephritis with small crescents. Her skin biopsy revealed a heavy neutrophil infiltrate involving the full thickness of the dermis with no evidence of a leucocytoclastic vasculitis, but was non-specific. She was initially commenced on intravenous lincomycin for her bloodstream infection and subsequently commenced on immunosuppression after cessation of hydralazine. The patient was subsequently discharged from hospital after a rapid clinical improvement. CONCLUSION: Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis is a rare adverse effect and can present with a severe vasculitic syndrome with multiple organ involvement. Features of this association include the presence of high titres of anti-myeloperoxidase-anti-neutrophil cytoplasmic antibody with multi-antigenicity, positive anti-histone antibodies and the lack of immunoglobulin and complement deposition histopathogically. A rash that is characteristic of Sweet's syndrome has also been described as an association. Prompt cessation of hydralazine may be sufficient to reverse disease activity but immunosuppression may be needed for definite treatment.

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.

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.

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.

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. METHODS: This is an observational cohort study of 30 men (age 54±13 years, body mass index (BMI) 28.1±5.8 kg/m2) and seven women (age 41±11 years, BMI 32.2±11.2 kg/m2) established on chronic home haemodialysis (3-5 h, 3.5-5 sessions weekly) who were converted to nocturnal home haemodialysis (6-9 h, 3.5-5 sessions weekly). Serum was collected at baseline and 6 months for measurement of TT, sex hormone binding globulin (SHBG), LH, FSH, prolactin, thyroid-stimulating hormone and thyroxine. RESULTS: In the male patients (n=25), serum prolactin significantly fell (281 (209.5-520) vs 243 (187-359) mU/L, P=0.001) and TT (12.6±5.8 vs 15.2±8.1 nmol/L, P=0.06) and FT (281±118 vs 359±221 pmol/L, P=0.01) increased. SHBG, LH and FSH were unchanged. At 6 months, two of the three women under 40 years of age had return of regular menses after being amenorrhoeic or having prolonged and irregular menses at baseline. There were insufficient women in this study to further analyse changes in sex hormone levels. Thyroid function tests remained stable. CONCLUSION: Alternate nightly nocturnal haemodialysis significantly improves hyperprolactinaemia and hypotestosteronaemia in men. Menstrual cycling may be re-established in young women. The effect of these changes on fertility has not been established. Patients should be counselled about the possibility of increased fertility before conversion to extended hours haemodialysis regimens.

Cardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: an interventional cohort study.

BACKGROUND: Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known. METHODS: Sixty-three patients on standard hemodialysis (SHD: 3.5-6 hours/session, 3-5 sessions weekly) converted to NHD (6-10 hours/session overnight for 3-5 sessions weekly). 2Dimensional transthoracic echocardiography and ultrasound measures of brachial artery reactivity (BAR), carotid intima-media thickness (CIMT), total arterial compliance (TAC) and augmentation index (AIX) were performed post dialysis at baseline and 18-24 months following conversion to NHD. In 37 patients, indices of oxidative stress: plasma malonyldialdehyde (MDA) and anti-oxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured at baseline, 3 and 6 months. RESULTS: Left ventricular mass index (LVMI) remained stable. Despite significant derangement at baseline, there were no changes in diastolic function measures, CIMT, BAR and TAC. AIX increased. Conversion to NHD improved bone mineral metabolism parameters and blood pressure control. Interdialytic weight gains increased. No definite improvements in measures of oxidative stress were demonstrated. CONCLUSIONS: Despite improvement in uremic toxin levels and some cardiovascular risk factors, conversion to an alternate nightly NHD regimen did not improve cardiovascular structure and function. Continuing suboptimal control of uremic toxins and interdialytic weight gains may be a possible explanation. This study adds to the increasing uncertainty about the nature of improvement in cardiovascular parameters with conversion to intensive hemodialysis regimens. Future randomized controlled trials will be important to determine whether increases in dialysis session duration, frequency or both are most beneficial for improving cardiovascular disease whilst minimizing costs and the impact of dialysis on quality of life.

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

BACKGROUND: Aluminium-containing phosphate binders have long been used for treatment of hyperphosphatemia in dialysis patients. Their safety became controversial in the early 1980's 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. DISCUSSION: The 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. SUMMARY: This 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.

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.

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.

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial).

BACKGROUND: The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet). METHODS: Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp(R), Amgen) for >or= 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements) will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA). Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration), and occurrence of adverse events (especially gastrointestinal adverse events). DISCUSSION: This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry number ACTRN12609000432213.

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 . 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.