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.

Construction of genetically engineered Streptococcus gordonii strains to provide control in QPCR assays for assessing microbiological quality of recreational water.

AIMS: Quantitative polymerase chain reaction (QPCR) methods for beach monitoring by estimating abundance of Enterococcus spp. in recreational waters use internal, positive controls which address only the amplification of target DNA. In this study two internal, positive controls were developed to control for both amplification and cell lysis in assays measuring abundance of vegetative Gram-positive bacteria. METHODS AND RESULTS: Controls were constructed using Streptococcus gordonii DL-1, a naturally transformable, Gram-positive bacterium. Unique target sequences were provided by chromosomal insertion of a genetically modified, green fluorescent protein gene fragment. Results suggest that their use for control of lysis and amplification may be of significant value. CONCLUSIONS: The use of these controls and the establishment of data quality objectives to determine the tolerable level of decision error should ensure that environmental decisions based on QPCR data are technically and scientifically sound. SIGNIFICANCE AND IMPACT OF THE STUDY: QPCR measurements related to cell abundance may vary between samples as thick-walled Gram-positive bacteria are inherently difficult to lyse and substances present in recreational waters may inhibit amplification. As QPCR methods are considered for beach monitoring, it is essential to demonstrate that the data obtained accurately reflects the abundance of the bacterial indicator.

Review Article: is it time to embrace haemodiafiltration for centre-based haemodialysis?

Improvements in survival in dialysis patients over the past few decades have been disappointing. Recent prospective trials such the haemodialysis study have not shown conclusive improvements. Two recent observational studies have found a striking survival advantage for haemodiafiltration (HDF). This review covers the differences between HDF and conventional haemodialysis (HD) and the history of the technological advances in the HDF technique. In addition, it explores the putative benefits of HDF over HD. While the observational studies provide a basis for optimism that HDF will provide benefit to dialysis patients, definitive conclusions cannot be drawn until the results of randomized controlled trials are available. While the evidence in favour of HDF at this stage is observational only, there are no studies suggesting that the treatment is detrimental. The use of HDF should probably be increased, particularly in centres where an increase in the frequency and duration of dialysis cannot be readily achieved.

A randomized controlled trial of fludrocortisone for the treatment of hyperkalemia in hemodialysis patients.

BACKGROUND: Previous small uncontrolled studies suggested that fludrocortisone may significantly decrease serum potassium concentrations in hemodialysis patients, possibly through enhancement of colonic potassium secretion. The aim of this study is to evaluate the effect of oral fludrocortisone on serum potassium concentrations in hyperkalemic hemodialysis patients in an open-label randomized controlled trial. METHODS: Thirty-seven hemodialysis patients with predialysis hyperkalemia were randomly allocated to administration of either oral fludrocortisone (0.1 mg/d; n = 18) or no treatment (control; n = 19) for 3 months. The primary outcome measure was midweek predialysis serum potassium concentration, which was measured monthly during the trial. Prospective power calculations indicated that the study had an 80% probability of detecting a decrease in serum potassium levels of 0.7 mEq/L (0.7 mmol/L). RESULTS: Baseline patient characteristics were similar, except for slightly longer total weekly dialysis hours in the fludrocortisone group (13.0 +/- 1.3 versus 12.1 +/- 1.0; P = 0.02). At the end of the study period, no significant changes in serum potassium concentrations were observed between the fludrocortisone and control groups (4.8 +/- 0.5 versus 5.2 +/- 0.7 mEq/L [mmol/L], respectively; P = 0.10). Similar results were obtained when changes in serum potassium levels over time were examined between the 2 arms by using repeated-measures analysis of variance, with or without adjustment for total weekly dialysis hours. Secondary outcomes, including predialysis mean arterial pressure, interdialytic weight gain, serum sodium level, and hospitalization for hyperkalemia, were not significantly different between groups. There were no observed adverse events. CONCLUSION: Administering fludrocortisone to hyperkalemic hemodialysis patients is safe and well tolerated, but does not achieve clinically important decreases in serum potassium levels.

Reversal of acidification in tributaries of the River Duddon (English Lake District) between 1970 and 1998.

Long-term changes in stream water chemistry in the upper Duddon catchment (southwest Lake District, UK) were investigated. Ten streams were sampled and analysed weekly during 1998, and the results compared with data for the early 1970s and 1986. The waters exhibited a range of pH, average values for 1998 being 5.04-7.04. For all the streams, the average pH in 1998 was greater than that during 1971-73. Statistical analysis was carried out, using the 1970s data to estimate the magnitude of inter-annual variation, and taking discharge into account on the basis of antecedent rainfall. The results showed that for two of the streams the pH increase was significant at the 2.5% level, while for a further three it was significant at the 10% level. Comparison of the 1998 concentrations of nitrate and non-marine sulphate with data obtained for five streams in 1973-74 showed that average nitrate concentration had increased from 11 to 20 microeq dm(-3) while that of non-marine sulphate had decreased from 94 to 50 microeq dm(-3). For four of the streams, comparisons were also made between the 1998 data and those for 1986. In three cases, pH in 1998 was generally higher, and Al generally lower, than the values for 1986, but in the fourth case little difference was evident. The present results support observations for five nearby standing waters, strengthening the evidence for a general reversal of acidification in the southwest part of Lake District, due to a decline in the deposition of pollutant sulphur.

Assessing resilience in adults with histories of childhood sexual abuse.

Adults with histories of childhood sexual abuse were categorized as being either resilient or nonresilient on the basis of current levels of depression and self-esteem. Characteristics of both the individual and the early family environment distinguished resilient from nonresilient abuse survivors, as did the physically coercive nature of the abuse experience.

Analysis of bacterial communities in seagrass bed sediments by double-gradient denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA genes.

Bacterial communities associated with seagrass bed sediments are not well studied. The work presented here investigated several factors and their impact on bacterial community diversity, including the presence or absence of vegetation, depth into sediment, and season. Double-gradient denaturing gradient gel electrophoresis (DG-DGGE) was used to generate banding patterns from the amplification products of 16S rRNA genes in 1-cm sediment depth fractions. Bioinformatics software and other statistical analyses were used to generate similarity scores between sections. Jackknife analyses of these similarity coefficients were used to group banding patterns by depth into sediment, presence or absence of vegetation, and by season. The effects of season and vegetation were strong and consistent, leading to correct grouping of banding patterns. The effects of depth were not consistent enough to correctly group banding patterns using this technique. While it is not argued that bacterial communities in sediment are not influenced by depth in sediment, this study suggests that the differences are too fine and inconsistent to be resolved using 1-cm depth fractions and DG-DGGE. The effects of vegetation and season on bacterial communities in sediment were more consistent than the effects of depth in sediment, suggesting they exert stronger controls on microbial community structure.

Randomized trial of FX high flux vs standard high flux dialysis for homocysteine clearance.

BACKGROUND: Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid-vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels. METHODS: A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B(6) 25 mg and folic acid 5 mg daily throughout the study. RESULTS: The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25+/-6.6 vs 25.9+/-5.8 microg/l, Delta95% CI = -2.77 to 4.59, P = 0.31. There was a non-significant trend toward a decrease in Hcy in both groups (27.43+/-7.68 to 25.91+/-5.78 micromol/l for SHF, P = 0.23 and 26.0+/-4.58 to 25.0+/-6.61 micromol/l for FX, P = 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted beta = -1.30, 95% CI = -2.41 to -0.19, P = 0.022). K(t)/V(urea) was higher in FX vs SHF (1.35+/-0.18 vs 1.22+/-0.2; P = 0.013). Folate and B(6) levels did not change. CONCLUSIONS: The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 mumol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis.

The psychological effects of work experiences and disagreements about gender role beliefs in dual-earner couples: a longitudinal study.

Using an economically diverse random sample of 300 full-time employed men and women in dual-earner couples from two communities in the Northeast, we estimated the relation between the direction and magnitude of disagreement about gender role ideology (GRI) within couples and psychological distress. We conceptualized GRI within couples as both the couple mean or stable gender-role ideology (the "couple ideology") and as each partner's deviation from the other partner's score. Moreover, for each partner, we estimated the relation between both the stable (i.e., mean) component and the change (i.e., time-varying) component of GRI and distress. Finally, for each partner we estimated the moderating effect of GRI on the relation between job-role quality and distress. Findings are: (a) the more egalitarian the husband's average GRI is relative to his wife's, the less distressed he is; (b) if over time a wife's GRI becomes less egalitarian relative to her husband's, then her distress will be more affected by changes in her job-role quality; (c) for husbands, as the couple's average GRI becomes more egalitarian over time, the effect of job-role quality on distress is lessened; and (d) for a man in a couple with a more egalitarian stable GRI, the effects of change in job-role quality on distress are less pronounced than for a man in a couple with a less egalitarian stable GRI. Results are discussed in terms of new conceptions of GRI revealing the dynamic interaction of within-couples' gender-role ideologies.

Comparison of bacterial and endotoxin retention by charge-modified sterilizing grade filters during intermittent long-term use.

There has been growing concern in recent years about control of bacterial bioburden and endotoxin in pharmaceutical water systems by both the pharmaceutical manufacturers and the Food and Drug Administration (FDA). This concern exists not only for Water for Injection (WFI) systems, but for any water system used in the manufacture of a product which could be affected by the microbial bioburden. In hot WFI systems, bioburden control is assured by keeping the water in the recirculating loops at 80 degrees C. At points of use in these systems, the temperature fluctuates and can be below sanitization temperature for extended periods. On the other hand, in cold water systems [WFI and deionized (DI)], both bioburden and endotoxin control are more difficult. This study shows that sterilizing grade, positively-charged filters can provide absolute bioburden control. In addition, these filters effectively retain high levels of both purified and cell-associated endotoxins over a five month period under severe intermittent system use conditions in a model high-purity water system. This study suggests a solution to the concerns over long-term use of bacterially retentive filters in properly maintained high-purity water systems.

Themes of power and betrayal in sexual abuse survivors' characterizations of interpersonal relationships.

Consistent with the notion that childhood sexual abuse (CSA) shapes motivational dispositions and internalized schemata that are reflected in adult characterizations of self and others, we hypothesized that adult CSA survivors' characterizations of interpersonal relationships would reflect greater power motivation as defined by McClelland and Winter, and more preoccupation with themes of powerlessness and betrayal than nonabused adult's - a pattern associated with poor psychological functioning. Stories written by women with CSA histories (n = 43) reflected both a greater need for and fear of power, and contained more themes of powerlessness and betrayal than stories written by women without CSA histories (n = 43). Frequency of sexual abuse in combination with fear of power was predictive of depression and low self-esteem.