Renal hyperparathyroidism- a risk factor in the development of encapsulating peritoneal sclerosis.

Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls. Methods: Linear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients. Results: EPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively. Conclusion: High levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.

A randomised controlled trial to examine the effects of cinacalcet on bone and cardiovascular parameters in haemodialysis patients with advanced secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism may lead to increased cardiovascular risk. The use of cinacalcet may improve bone and cardiovascular health with improved parathormone (PTH) and phosphate control. METHODS: This is an open-label prospective randomised controlled trial to compare progression of cardiovascular and chronic kidney disease mineral and bone disorder (CKD-MBD) parameters. Patients were randomised to receive cinacalcet alongside standard therapy or standard therapy alone. Thirty-six haemodialysis patients who had > 90 days on dialysis, iPTH > 300 pg/mL, calcium > 2.1 mmol/L and age 18-75 years were included. Following randomization, all 36 patients underwent an intensive 12-week period of bone disease management aiming for iPTH 150-300 pg/mL. The primary outcome was change in vascular calcification using CT agatston score. Secondary outcomes included pulse wave velocity (PWV), left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), augmentation index (Aix) and bone measurements. The above measurements were obtained at baseline and 12 months. RESULTS: There was no evidence of a group difference in the progression of calcification (median change (IQR) cinacalcet: 488 (0 to1539); standard therapy: 563 (50 to 1214)). In a post hoc analysis combining groups there was a mean (SD) phosphate reduction of 0.3 mmol/L (0.7) and median (IQR) iPTH reduction of 380 pg/mL (- 754, 120). Regression of LVMI and CIMT was seen (P = 0.03 and P = 0.001) and was significantly associated with change of phosphate on multi-factorial analyses. CONCLUSIONS: With a policy of intense CKD-MBD parameter control, no significant benefit in bone and cardiovascular markers was seen with the addition of cinacalcet to standard therapy over one year. Tight control of hyperphosphataemia and secondary hyperparathyroidism may lead to a reduction in LVMI and CIMT but this needs further investigation. Although the sample size was small, meticulous trial supervision resulted in very few protocol deviations with therapy.

Prescribing high-quality peritoneal dialysis: Moving beyond urea clearance.

Urea removal in peritoneal dialysis (PD) has been a primary measure of dialysis adequacy, but its utility remains limited due to its poor correlation with the clearance of other important uraemic retention solutes and the low certainty of evidence relating peritoneal urea clearance and survival of individuals doing PD. Indeed, clearances of other uraemic solutes, electrolyte imbalances, hypoalbuminaemia and nutritional status, may provide a more holistic measure of dialysis adequacy when evaluating individuals on PD in addition to focusing on person-centred outcomes. Here, we review the history of the urea and creatinine-centric approach to dialysis adequacy and explore the potential importance of other uraemic retention solutes, electrolyte disturbances, phosphorus control, peritoneal protein losses and hypoalbuminaemia, as well as nutritional management to promote a broader multidimensional concept of clearance for PD.

Hyperphosphataemia in 2019: have we made progress?

PURPOSE OF REVIEW: This review describes recent developments in the management of serum phosphate in dialysis patients, with a focus on the development of recent trials which randomize patients to different levels of control. RECENT FINDINGS: We review the uncertainties around clinical benefits of serum phosphate control and alternative approaches to current management, as well as a multinational attempt to conduct randomized controlled trials in this area. We discuss novel methods of limiting oral phosphate absorption. SUMMARY: Although numerous guidelines and target ranges for serum phosphate management exist, they are largely based on observational data and there is no definitive evidence that good control improves the length or quality of life of dialysis patients. New phosphate binders continue to appear on the market with increasing financial cost but without additional meaningful outcome data. Two recently published trials have demonstrated the feasibility of a large-scale study of differing phosphate levels to test the hypothesis that reduction of serum phosphate is beneficial to dialysis patients. Restriction of oral phosphate intake should not be overlooked.

A randomized controlled trial of different serum phosphate ranges in subjects on hemodialysis.

BACKGROUND: Hyperphosphataemia in dialysis subjects is associated with increased mortality. However cause and effect has not been proven, and the ideal phosphate target range is unknown despite KDOQI's call for studies over 12 years ago. The design and conduct of a randomized controlled trial is challenging because maintaining two groups within differing target ranges of serum phosphate has not been achieved over a long follow-up of 1 year, in a trial setting, before. The SPIRiT study examines the subject acceptance, recruitment and retention rates for such a study in which subjects were randomised to two distinct serum phosphate concentrations, then titrated and maintained over 12 months. METHODS: A two center trial of 104 hemodialysis subjects randomized to lower range LRG 0.8-1.4 mmol/L or 2.5-4.3 mg/dL) and higher range (HRG 1.8-2.4 mmol/L or 5.6-7.4 mg/dL) serum phosphate groups. Two months' titration and ten months' maintenance phase. Interventions were non-calcium phosphate binders, self-help questionnaires, with blood tests at specified time intervals. RESULTS: Thirteen percent of the eligible dialysis population were successfully recruited. A mean separation by serum phosphate of 1.1 mg/dL was achieved and maintained between the groups over 10 months. Drop-out rate was 27% with mortality 10%. Nine subjects in the HRG (17.6%) and two subjects in the LRG (3.8%) died during the study, however the study was not powered to detect significant differences in outcomes. CONCLUSION: Randomizing dialysis subjects to separate treatment targets for serum phosphate can achieve a clinically significant sustained separation over 12 months. A large scale longer term study is required to examine outcomes including mortality. TRIAL REGISTRATION: The trial registration number is ISRCTN24741445 - Date of registration 16th January, retrospectively registered.

Long-Term Mortality and Bone Safety in Patients with End-Stage Renal Disease Receiving Lanthanum Carbonate.

BACKGROUND/AIMS: This post-marketing observational study assessed the long-term safety of lanthanum carbonate (LaC) in US patients with end-stage renal disease (NCT00567723). METHODS: Patients (≥18 years old) undergoing dialysis, who had Medicare as their primary healthcare payer, and records in the United States Renal Data System were followed-up for 5 years. Patients who had received LaC for at least 12 consecutive weeks formed the exposed cohort. During the same time period, patients who had undergone dialysis for at least 12 consecutive weeks and had been treated with any other phosphate binder formed the primary comparator cohort. A historical cohort was also evaluated. Primary outcomes were all-cause mortality, and time to and incidence of first bone-fracture event requiring hospitalization. Secondary outcomes were time to first occurrence of and incidence of specific gastrointestinal (GI) disease, liver disease, malignancy, and major infectious episode requiring hospitalization. -Results: 2,026 and 8,094 patients were included in the exposed and primary comparator cohorts, respectively. A Cox proportional hazards model showed that patients receiving LaC were not at increased risk of all-cause mortality (adjusted hazard ratio 0.94; 95% CI 0.88-1.01; p = 0.078), bone fractures (0.86; 0.71-1.05; p = 0.130), specific GI disease (0.86; 0.76-0.97; p = 0.015), liver disease (0.88; 0.70-1.09; p = 0.236), malignancy (0.85; 0.54-1.34; p = 0.496), or major infectious episodes (0.87; 0.80-0.94; p < 0.001) requiring hospitalization compared with primary comparator patients. CONCLUSIONS: LaC was not associated with increased risk of mortality, bone fractures, or any secondary outcome.

A Multifaceted Quality Improvement Programme to Improve Acute Kidney Injury Care and Outcomes in a Large Teaching Hospital.

Acute kidney injury (AKI) is now widely recognised as a serious health care issue, occurring in up to 25% of hospital in-patients, often with worsening of outcomes. There have been several reports of substandard care in AKI. This quality improvement (QI) programme aimed to improve AKI care and outcomes in a large teaching hospital. Areas of documented poor AKI care were identified and specific improvement activities implemented through sequential Plan-Do-Study-Act (PDSA) cycles. An electronic alert system (e-alert) for AKI was developed, a Priority Care Checklist (PCC) was tested with the aid of specialist nurses whilst targeted education activities were carried out and data on care processes and outcomes monitored. The e-alert had a sensitivity of 99% for the detection of new cases of AKI. Key aspects of the PCC saw significant improvements in their attainment: Detection of AKI within 24 hours from 53% to 100%, fluid assessment from 42% to 90%, drug review 48% to 95% and adherence to nine key aspects of care from 40% to 90%. There was a significant reduction in variability of delivered AKI care. AKI incidence reduced from 9% of all hospitalisations at baseline to 6.5% (28% reduction), AKI related length of stay reduced from 22.1 days to 17 days (23% reduction) and time to recovery (AKI days) 15.5 to 9.8 days (36% reduction). AKI related deaths also showed a trend towards reduction, from an average of 38 deaths to 34 (10.5%). The number of cases of hospital acquired AKI were reduced by 28% from 120 to 86 per month. This study demonstrates significant improvements related to a QI programme combining e-alerts, a checklist implemented by a nurse and education in improving key processes of care. This resulted in sustained improvement in key patient outcomes.

Lanthanum carbonate: safety data after 10 years.

Despite 10 years of post-marketing safety monitoring of the phosphate binder lanthanum carbonate, concerns about aluminium-like accumulation and toxicity persist. Here, we present a concise overview of the safety profile of lanthanum carbonate and interim results from a 5-year observational database study (SPD405-404; ClinicalTrials.gov identifier: NCT00567723). The pharmacokinetic paradigms of lanthanum and aluminium are different in that lanthanum is minimally absorbed and eliminated via the hepatobiliary pathway, whereas aluminium shows appreciable absorption and is eliminated by the kidneys. Randomised prospective studies of paired bone biopsies revealed no evidence of accumulation or toxicity in patients treated with lanthanum carbonate. Patients treated with lanthanum carbonate for up to 6 years showed no clinically relevant changes in liver enzyme or bilirubin levels. Lanthanum does not cross the intact blood-brain barrier. The most common adverse effects are mild/moderate nausea, diarrhoea and flatulence. An interim Kaplan-Meier analysis of SPD405-404 data from the United States Renal Data System revealed that the median 5-year survival was 51.6 months (95% CI: 49.1, 54.2) in patients who received lanthanum carbonate (test group), 48.9 months (95% CI: 47.3, 50.5) in patients treated with other phosphate binders (concomitant therapy control group) and 40.3 months (95% CI: 38.9, 41.5) in patients before the availability of lanthanum carbonate (historical control group). Bone fracture rates were 5.9%, 6.7% and 6.4%, respectively. After more than 850 000 person-years of worldwide patient exposure, there is no evidence that lanthanum carbonate is associated with adverse safety outcomes in patients with end-stage renal disease.

Dissolution of extensive urolithiasis: extending the utility of rasburicase can avoid the need for surgical intervention and renal replacement therapy.

A 79-year-old male with chronic myelomonocytic leukaemia and extensive bilateral renal stone disease was treated with intravenous rasburicase for persistent hyperuricaemia. Subsequent imaging revealed a complete dissolution of stone burden, avoiding the need for complex, invasive stone surgery and further renal replacement therapy.

A Study to Inform the Design of a National Multicentre Randomised Controlled Trial to Evaluate If Reducing Serum Phosphate to Normal Levels Improves Clinical Outcomes including Mortality, Cardiovascular Events, Bone Pain, or Fracture in Patients on Dialysis.

UNLABELLED: Background. Retrospective, observational studies link high phosphate with mortality in dialysis patients. This generates research hypotheses but does not establish "cause-and-effect." A large randomised controlled trial (RCT) of about 3000 patients randomised 50 : 50 to lower or higher phosphate ranges is required to answer the key question: does reducing phosphate levels improve clinical outcomes? Whether such a trial is technically possible is unknown; therefore, a study is necessary to inform the design and conduct of a future, definitive trial. Methodology. Dual centre prospective parallel group study: 100 dialysis patients randomized to lower (phosphate target 0.8 to 1.4 mmol/L) or higher range group (1.8 to 2.4 mmol/L). Non-calcium-containing phosphate binders and questionnaires will be used to achieve target phosphate. PRIMARY ENDPOINT: percentage successfully titrated to required range and percentage maintained in these groups over the maintenance period. Secondary endpoints: consent rate, drop-out rates, and cardiovascular events. Discussion. This study will inform design of a large definitive trial of the effect of phosphate on mortality and cardiovascular events in dialysis patients. If phosphate lowering improves outcomes, we would be reassured of the validity of this clinical practice. If, on the other hand, there is no improvement, a reassessment of resource allocation to therapies proven to improve outcomes will result. Trial Registration Number. This trial is registered with ISRCTN registration number ISRCTN24741445.

Acute arteriovenous access failure: long-term outcomes of endovascular salvage and assessment of co-variates affecting patency.

AIMS: This study reports long-term outcomes after endovascular salvage (EVS) for acute dialysis fistula/graft dysfunction. METHODS: All patients presenting with acute fistula or graft dysfunction, excluding primary failures, referred for endovascular salvage were included in this single-centre prospective study. RESULTS: Altogether, 410 procedures were carried out in 232 patients. Overall, the incidence of thrombosis/occlusion (per patient-year) was 0.12 for fistulae and 0.9 for grafts. The anatomical success rate for EVS was 94% for fistulae and 92% for grafts. Primary patency rates for fistulae at 1, 6, 12, 24 and 36 months were 82, 64, 44, 34 and 26%, respectively, whereas secondary patency rates were 88, 84, 74, 69 and 61%, respectively. Primary patency rates for grafts at 1, 6 and 12 months were 50, 14 and 8%. The overall rate of complications was 6% with no incidence of symptomatic pulmonary embolism. In a Cox regression model, upper-arm location of fistula (HR 1.9, p = 0.04, n = 144) was associated with lower primary patency, whereas the presence of thrombosis was associated lower primary (HR 1.9, p = 0.004, n = 144) and secondary patency (HR 3.7, p < 0.001, n = 144). Aspirin therapy was associated with longer primary patency (HR 0.6, p = 0.02, n = 144) and secondary patency (HR 0.58, p = 0.08, n = 144). CONCLUSION: EVS is effective but longer-term outcomes are poor. Presence of thrombosis portends poor fistula survival and strategies for prevention need attention. Balloon maceration, our preferred declotting technique, is safe and the most cost-effective method. Aspirin therapy for patients presenting with failure of fistulae deserves further investigation.

Novel phosphate binders: plus ça change, plus c'est la même chose.

Sucroferric oxyhydroxide is a new calcium-free polynuclear iron(III)-oxyhydroxide compound that binds phosphate by ligand exchange. Floege et al. report equivalent phosphate control with a mean dose of three pills daily compared with eight of sevelamer, and suggest that a reduced pill burden may represent an aid to improved adherence. However, there is still no prospective interventional study to demonstrate that reduction in serum phosphate improves patient outcomes for any oral phosphate binder.

Profiling patient attitudes to phosphate binding medication: a route to personalising treatment and adherence support.

OBJECTIVE: Nonadherence to phosphate binding medication (PBM) compromises the efficacy of treatment for chronic kidney disease, but its causes are poorly understood. This study sought to explore patient attitudes towards PBM and to evaluate the utility of the necessity-concerns framework for understanding adherence to PBM. DESIGN: A sample of 221 dialysis patients currently prescribed PBM were surveyed from eight UK renal units. MAIN OUTCOME MEASURES: Demographic data and clinical information, alongside the Beliefs about Medicines Questionnaire and the medication adherence report scale were reported. RESULTS: Low adherence to PBM was predicted by reduced beliefs in personal need for PBM (OR = .34; 95% CI: .14-.83; p < .05), and increased concerns about PBM (OR = 3.17; 95% CI: 1.87-5.37; p < .001). Patients were categorised into attitudinal groups based on their beliefs about PBM and being 'skeptical' of PBM (low necessity beliefs and high concerns) was most associated with low adherence. CONCLUSION: Strategies to improve adherence to PBM should aim to elicit and address patients' beliefs about their personal need for PBM and their concerns about this medication.

Incidence and consequence of acute kidney injury in unselected emergency admissions to a large acute UK hospital trust.

BACKGROUND: AKI is common among hospital in-patients and places a huge financial burden on the UK National Health Service, causing increased length of hospital stay and use of critical care services, with increased requirement for complex interventions including dialysis. This may account for up to 0.6% of the total Health Service budget. To investigate the incidence and consequences of AKI, all unselected emergency admissions to a large acute UK single centre University Teaching Hospital over two separate 7 day periods were reviewed. METHODS: A retrospective audit of 745 case records was undertaken (54.6% male) including laboratory data post-discharge or death, with classification of AKI by RIFLE, AKIN and AKIB criteria. Participants were included whether admitted via their general practitioners, the emergency department, or as tertiary specialty transfers. Outcome measures were presence or absence of AKI recorded using each of the three AKI criteria, length of hospital stay (LOS), admission to, and LOS in critical care, and mortality. The most severe grade of AKI only, at any time during the admission, was recorded to prevent double counting. Renal outcome was determined by requirement for renal replacement therapy (RRT), and whether those receiving RRT remained dialysis dependent or not. RESULTS: AKI incidence was 25.4% overall. With approximately one third present on admission and two thirds developing post admission. The AKI group had LOS almost three times higher than the non AKI group (10 vs 4 days). Requirement for critical care beds was 8.1% in the AKI group compared to 1.7% in non AKI group. Overall mortality was 5.5%, with the AKI group at 11.4% versus 3.3% in the non AKI group. CONCLUSIONS: AKI in acute unselected hospital admissions is more common than existing literature suggests, affecting 25% of unselected admissions. In many this is relatively mild and may resolve spontaneously, but is associated with increased LOS, likelihood of admission to critical care, and risk of death. If targeted effective interventions can be developed it seems likely that substantial clinical benefits for the patient, as well as financial and structural benefits for the healthcare organisation may accrue.

Outcomes of peritoneal dialysis patients and switching to hemodialysis: a competing risks analysis.

BACKGROUND: We performed a review of a large incident peritoneal dialysis cohort to establish the impact of current practice and that of switching to hemodialysis. METHODS: Patients starting peritoneal dialysis between 2004 and 2010 were included and clinical data at start of dialysis recorded. Competing risk analysis and Cox proportional hazards model with time-varying covariate (technique failure) were used. RESULTS: Of 286 patients (median age 57 years) followed for a median of 24.2 months, 76 were transplanted and 102 died. Outcome probabilities at 3 and 5 years respectively were 0.69 and 0.53 for patient survival (or transplantation) and 0.33 and 0.42 for technique failure. Peritonitis caused technique failure in 42%, but ultrafiltration failure accounted only for 6.3%. Davies comorbidity grade, creatinine and obesity (but not residual renal function or age) predicted technique failure. Due to peritonitis deaths, technique failure was an independent predictor of death hazard. When successful switch to hemodialysis (surviving more than 60 days after technique failure) and its timing were analyzed, no adverse impact on survival in adjusted analysis was found. However, hemodialysis via central venous line was associated with an elevated death hazard as compared to staying on peritoneal dialysis, or hemodialysis through a fistula (adjusted analysis hazard ratio 1.97 (1.02 - 3.80)). CONCLUSIONS: Once the patients survive the first 60 days after technique failure, the switch to hemodialysis does not adversely affect patient outcomes. The nature of vascular access has a significant impact on outcome after peritoneal dialysis failure.

Variability in parathyroid hormone assays confounds clinical practice in chronic kidney disease patients.

BACKGROUND: Intact parathyroid hormone (iPTH) measurements are used to guide therapy in renal patients, but variability in results can occur depending on the assay used. This study has investigated iPTH assay variation in North West England and paired data with regional audit data to determine clinical relevance of assay variability. METHODS: Thirty-seven haemodialysis patients had blood taken (EDTA plasma, and serum), and samples were processed at 17 laboratories that analyse iPTH for North West dialysis patients. Correction factors were calculated and applied to the iPTH assay results to enable direct comparisons. These correction factors were also applied to Regional Audit data to determine if iPTH assay variability explains the variation in unit performance in achieving PTH targets. RESULTS: The iPTH results from the 37 patients were significantly different when either analysed by different assays and/or different laboratories (P < 0.001). The Abbott Architect method consistently produced the highest iPTH results. Of the 37 patients, between 49% and 65% would achieve the Kidney Disease: Improving Global Outcomes (KDIGO) iPTH target depending on the assay used. When results were adjusted using correction factors, 21% of the patients would require a change of management according to guidelines. Data from all haemodialysis units submitted for the regional audit were adjusted to the Roche assay and this led to a small change in achievement of KDIGO iPTH targets in individual units when compared to each other. CONCLUSIONS: A combination of iPTH assay variability and diversity in clinical management leads to variation in achieving iPTH targets. Both need to be improved and/or standardized to improve patient care.

Lanthanum carbonate versus placebo for management of hyperphosphatemia in patients undergoing peritoneal dialysis: a subgroup analysis of a phase 2 randomized controlled study of dialysis patients.

BACKGROUND: This short-term study assessed the efficacy and safety of lanthanum carbonate in the treatment of hyperphosphatemia in dialysis patients; here, we report a prespecified subgroup analysis of patients undergoing peritoneal dialysis. METHODS: Men and women (n=39) who had received continuous ambulatory peritoneal dialysis for chronic kidney disease for 6 months or more were enrolled in eight renal medicine departments in the United Kingdom. A 2-week washout period was followed by a 4-week dose-titration phase during which patients received lanthanum carbonate titrated up to 2250 mg/day. This was followed by a 4-week, randomized, placebo-controlled, parallel-group phase during which patients continued to receive either lanthanum carbonate at the titrated dose, or a matched dose of placebo. The main outcome measure was control of serum phosphate levels (1.3-1.8 mmol/l) at the end of the parallel-group phase. RESULTS: Serum phosphate was controlled in 3/39 (8%) patients at the beginning of the dose-titration phase (after washout) and in 18/31 (58%) patients treated with lanthanum carbonate at its end. After the parallel-group phase, 60% of lanthanum carbonate-treated patients and 10% of those receiving placebo had controlled serum phosphate. There was no difference in mean (95% confidence interval) serum phosphate levels between groups at randomization: lanthanum carbonate, 1.57 (1.34-1.81) mmol/l; placebo, 1.58 (1.40-1.76) mmol/l (p=0.96). However, a difference was seen at the end of the parallel-group phase: lanthanum carbonate, 1.56 (1.33-1.79) mmol/l; placebo, 2.25 (1.81-2.68) mmol/l (p=0.0015). There were no clinically important changes in nutritional parameters and no serious treatment-related adverse events were recorded. CONCLUSIONS: At doses up to 2250 mg/day, lanthanum carbonate is well tolerated and controls hyperphosphatemia effectively. Treatment with higher doses of lanthanum carbonate may allow patients undergoing peritoneal dialysis the potential to increase their dietary protein intake without compromising their phosphate control.

Use of magnesium as a drug in chronic kidney disease.

From chronic kidney disease (CKD) Stage 4 onwards, phosphate binders are needed in many patients to prevent the development of hyperphosphataemia, which can result in disturbed bone and mineral metabolism, cardiovascular disease and secondary hyperparathyroidism. In this review, we re-examine the use of magnesium-containing phosphate binders for patients with CKD, particularly as their use circumvents problems such as calcium loading, aluminum toxicity and the high costs associated with other agents of this class. The use of magnesium hydroxide in the 1980s has been superseded by magnesium carbonate, as the hydroxide salt was associated with poor gastrointestinal tolerability, whereas studies with magnesium carbonate show much better gastrointestinal profiles. The use of combined magnesium- and calcium-based phosphate binder regimens allows a reduction in the calcium load, and magnesium and calcium regimen comparisons show that magnesium may be as effective a phosphate binder as calcium. A large well-designed trial has recently shown that a drug combining calcium acetate and magnesium carbonate was non-inferior in terms of lowering serum phosphate to sevelamer-HCl and had an equally good tolerability profile. Because of the high cost of sevelamer and lanthanum carbonate, the use of magnesium carbonate could be advantageous and drug acquisition cost savings would compensate for the cost of introducing routine magnesium monitoring, if this is thought to be necessary and not performed anyway. Moreover, given the potential cost savings, it may be time to re-investigate magnesium-containing phosphate binders for CKD patients with further well-designed clinical research using vascular end points.

Pharmacology, efficacy and safety of oral phosphate binders.

The ideal serum level of phosphate in patients on dialysis, and the benefits of controlling levels of phosphate in serum remain unclear despite observational studies that associate phosphate levels with mortality. In the absence of robust data from trials, current guidelines are necessarily based on opinion. Oral phosphate binders are required by the majority of patients on dialysis, and all of these binders can control serum levels of phosphate to similar degrees. Patient preference and adherence to prescribed therapy is at least as important as the efficacy of the prescribed binder. Avoidance of calcium-containing binders has become accepted practice where the alternatives are affordable, but incontrovertible evidence in favor of this approach is lacking. Use of sevelamer and lanthanum avoids calcium loading, but at considerable financial cost and with no reliable patient outcome data to prove their value. Additional approaches to aid control of serum levels of phosphate include blockade of gastrointestinal phosphate absorption and possibly binding of salivary phosphate. Importantly, the role of phosphate control in determining patient outcomes must be quantified, which is likely to require a large randomized, controlled study of two levels of phosphate control. Without such a study we will continue to rely on observational data with all its uncertainties and potential to mislead.