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.

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.

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.