Phosphate-Binder Use in US Dialysis Patients: Prevalence, Costs, Evidence, and Policies.

Medicare costs for phosphate binders for US dialysis patients and patients with chronic kidney disease enrolled in Medicare Part D exceeded $1.5 billion in 2015. Previous data have shown that Part D costs for mineral and bone disorder medications increased faster than costs for all Part D medications for dialysis patients. Despite extensive use of phosphate binders and escalating costs, conclusive evidence is lacking that they improve important clinical end points in dialysis patients or non-dialysis-dependent patients with chronic kidney disease. Using dialysis patient data from the US Renal Data System and laboratory information from the Centers for Medicare & Medicaid Services (CMS) CROWNWeb data, we update information on trends in phosphate-binder use, calcium and phosphorus values, and costs for Medicare-covered dialysis patients. We discuss these results in the context of evidence from clinical trials, meta-analyses, and observational studies evaluating phosphate-binder efficacy, safety, comparative effectiveness, and cost-effectiveness. Based on our analysis, we note a need for US Food and Drug Administration guidance regarding clinical evaluation of new phosphate binders, and we suggest that it would be in CMS' best interest to fund a clinical trial to assess whether lower versus higher phosphate concentrations improve hard clinical outcomes, and if so, whether particular phosphate binders are superior to placebo or other binders in improving these outcomes.

The Efficacy and Safety of Megestrol Acetate in Protein-Energy Wasting due to Chronic Kidney Disease: A Systematic Review.

OBJECTIVE: To assess the efficacy and safety of oral megestrol acetate (MA) in the management of protein-energy wasting in patients with chronic kidney disease (CKD). DESIGN: A systematic review of English published literature from 1970 until April 1, 2014. SUBJECTS: All adult patients with CKD including both dialysis and non-dialysis-dependent. INTERVENTION: Oral MA. MAIN OUTCOME MEASURE: Efficacy outcomes included changes in body weight, serum albumin, and appetite. Safety outcomes examined included adverse events (AEs) and deaths. RESULTS: A total of 9 studies met the inclusion criteria. No data on MA in non-dialysis CKD patients were available. Statistically significant increases in body weight (range 1.5-5 kg) were reported in 6 trials. Statistically significant increases in albumin (range of 0.22 g/dL-0.52 g/dL) were observed in 5 trials. Improved appetite was observed in 7 trials. All trials were limited by small sample sizes (range 9-32 subjects), short duration (range 8-24 weeks), a high degree of bias, and absence of clinical outcomes such as quality of life or hospitalizations. Forty-seven AEs were reported and included overhydration/excessive fluid gain, diarrhea, hyperglycemia, excessive weight gain, suppressed cortisol levels, thrombophlebitis, nausea/vomiting, confusion/hallucinations, vaginal bleeding, headache/dizziness, and elevated lactate dehydrogenase. There were 26 discontinuations due to death. CONCLUSION: The current evidence for treatment with MA in patients receiving dialysis is sparse with few high-quality trials. The safety of using MA beyond 24 weeks is unknown, and use of MA is associated with significant AEs. At this time, oral MA should be used with significant caution, and only when other treatment options are unavailable.

New models of chronic kidney disease care including pharmacists: improving medication reconciliation and medication management.

PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) are complex, have many medication-related problems (MRPs) and high rates of medication nonadherence, and are less adherent to some medications than patients with higher levels of kidney function. Nonadherence in CKD patients increases the odds of uncontrolled hypertension, which can increase the risk of CKD progression. This review discusses reasons for gaps in medication-related care for CKD patients, pharmacy services to reduce these gaps and successful models that incorporate pharmacist care. RECENT FINDINGS: Pharmacists are currently being trained to deliver patient-centred care, including identification and management of MRPs and helping patients overcome barriers to improve medication adherence. A growing body of evidence indicates that pharmacist services for CKD patients, including medication reconciliation and medication therapy management, positively affect clinical and cost outcomes, including lower rates of decline in glomerular filtration rates, reduced mortality and fewer hospitalizations and hospital days, but more robust research is needed. Team-based models including pharmacists exist today and are being studied in a wide range of innovative care and reimbursement models. SUMMARY: Opportunities are growing to include pharmacists as integral members of CKD and dialysis healthcare teams to reduce MRPs, increase medication adherence and improve patient outcomes.

Canadian Society of Nephrology commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD.

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for anemia management in patients with chronic kidney disease provides the structural and evidence base for the Canadian Society of Nephrology commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 11 of the 61 KDIGO guideline statements. Specifically, we agreed that a therapeutic trial of iron is appropriate in cases in which a reduction in erythropoiesis-stimulating agent (ESA) dosage or avoidance of ESA and transfusion is desired, transferrin saturations are >30%, and ferritin concentrations are >500 µg/L. However, we concluded that there is insufficient evidence to support an upper target or threshold for ferritin and transferrin saturation levels. We agree with the initiation of ESA treatment when hemoglobin (Hb) level is 90-100 g/L; however, we specifically state that an acceptable range for Hb level is 95-115 g/L, with a target of 100-110 g/L, and add caution to individualization above this range due to concerns regarding the safety of ESAs. We agree that ESAs should be used with considerable caution in patients with active malignancy, history of stroke, or history of malignancy, and we suggest initiating ESA therapy at Hb level of 90 g/L and to aim for a Hb level in the range of 90-105 g/L. The reader is encouraged to note the level of evidence and review the entire KDIGO anemia guideline to interpret the guideline statements and commentary appropriately.

Cost analysis of an intravenous to subcutaneous epoetin α conversion.

BACKGROUND/AIMS: A cost analysis of a conversion from intravenous (IV) to subcutaneous (SC) epoetin α in patients receiving chronic in-center hemodialysis (HD). METHODS: This retrospective analysis compared epoetin α drug costs during a 6-month period of IV usage (July to December 2010, period 1) to a 6-month period of SC usage (July to December 2011, period 2) in four large in-center HD units. Data were collected from quarterly counts of HD patients receiving epoetin α and monthly inventory billing records. RESULTS: 622 HD patients who received IV epoetin α (period 1) were compared to 609 HD patients who received SC epoetin α (period 2). A 12.6% decrease in dose was observed. The average weekly cost of epoetin α was USD 173.02 per patient during the IV period versus USD 151.20 per patient during the SC period. This equated to a yearly cost savings of USD 1,135 per patient with SC epoetin α. CONCLUSION: The switch from IV to SC epoetin α was successfully implemented in all four centers and realized significant cost savings.

Focused Jurisdictional Scan of Glomerulonephritis Medication Access in Canada: A Program Report.

Purpose of Program: Glomerulonephritis (GN) is a group of rare kidney diseases that is increasingly being managed with higher cost immunosuppressive (IS) agents in Canada. Ontario Health's Ontario Renal Network (ORN) oversees the management and delivery of GN services in the province. Stakeholder surveys previously conducted by ORN identified that both clinicians and patients do not perceive access to GN medications as comprehensive or timely. The program conducted a focused jurisdictional scan among 7 provinces to inform ORN initiatives to improve access to GN medications. Specifically, the program examined clinician experience with GN access, public drug coverage criteria, and timelines for public coverage for select IS agents (ie, tacrolimus, cyclosporine, mycophenolate mofetil [MMF], mycophenolate sodium, rituximab, and eculizumab) used to manage GN in adults who live in Canada. Methods: For the selected IS agents, a focused jurisdictional scan on medication access was conducted by ORN in 2018 and updated in July 2022. Information was obtained by searching the gray literature and/or credible online sources for public funding policies and eligibility criteria. Findings were supplemented by personal communications with provincial drug programs and consulting GN clinical experts from 7 provinces (ie, Alberta, British Columbia, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Quebec). Key Findings: Clinicians from different provinces prescribe IS agents similarly for GN indications, despite distinctions in public drug funding policies. While patients can obtain public funding for many IS agents, for GN, most provinces rely on case-by-case review processes. In addition, provinces can vary in their funding criteria and which IS agents are listed on the public formulary. For IS agents that require prior authorization or case-by-case review, timelines vary by province with decisions taking a few days to weeks. British Columbia, with a GN-specific drug formulary, had the most integrated and efficient system for patients and prescribers. Limitations: This scan primarily relied on publicly available information for drug coverage criteria and clinician experience with access in their province. Since this scan was conducted, public drug coverage criteria and/or application processes may have changed. Implications: While patients in most provinces have similar needs and nephrologists similar prescribing patterns, gaps still exist for publicly funded GN medications. Interprovincial differences in the drugs funded, funding criteria, and application process may affect timely and equitable access to GN medications across Canada. Given the rarity of GN, a pan-Canadian funding approach may be warranted to improve the current state.

Objectif du programme: Les glomérulonéphrites (GN) sont un groupe de néphropathies rares qui sont de plus en plus fréquemment traitées avec les agents immunosuppresseurs (IS) coûteux au Canada. Le Réseau rénal de l'Ontario (ORN­Ontario Renal Network) de Santé Ontario supervise la gestion et la prestation des services liés à la GN dans cette province. Des enquêtes menées précédemment par l'ORN auprès des parties prenantes ont révélé que tant les cliniciens que les patients ne percevaient pas l'accès aux médicaments pour traiter la GN comme complet ou opportun. Le programme a mené une analyse ciblée des territoires de compétences dans sept provinces afin d'orienter les initiatives de l'ORN ayant pour objectif d'améliorer l'accès aux médicaments pour traiter la GN. Plus précisément, le programme a examiné l'expérience des cliniciens en matière d'accès aux médicaments pour traiter la GN, les critères d'admissibilité au régime public d'assurance-médicaments et les délais de couverture publique de certains agents IS (p. ex., tacrolimus, cyclosporine, mycophénolate mofétil [MMF], mycophénolate sodique, Rituximab, éculizumab) utilisés pour traiter la GN chez les adultes canadiens. Méthodologie: Une analyse ciblée des territoires de compétences quant à l'accès aux médicaments a été réalisée par l'ORN en 2018 et mise à jour en juillet 2022. L'information quant aux politiques de financement public et aux critères d'admissibilité a été obtenue en effectuant une recherche dans la littérature grise et des sources crédibles en ligne. Les résultats ont été complétés par des communications directes avec les régimes provinciaux d'assurance-médicaments et des experts cliniques de la GN de sept provinces (Alberta, Colombie-Britannique, Saskatchewan, Manitoba, Ontario, Nouvelle-Écosse et Québec). Principaux résultats: Les cliniciens des différentes provinces prescrivent des agents IS de façon similaire pour les indications liées à la GN, malgré des distinctions dans les politiques publiques de financement des médicaments. Bien que les patients bénéficient d'une couverture publique pour de nombreux agents IS, pour le traitement de la GN, la plupart des provinces s'appuient sur des processus d'examen au cas par cas. De plus, il peut exister des différences entre les provinces en ce qui concerne les critères de financement et les agents IS qui figurent sur leur formulaire public. Dans le cas des agents IS nécessitant une autorisation au préalable ou un examen au cas par cas, les délais varient d'une province à l'autre; les décisions pouvant prendre de quelques jours à quelques semaines. La Colombie-Britannique, qui dispose d'un formulaire de médicaments pour traiter spécifiquement la GN, présente le système le plus intégré et le plus efficace pour les patients et les prescripteurs. Limites: Cette analyse s'est principalement appuyée sur des renseignements accessibles au public en ce qui concerne les critères de couverture des médicaments et l'expérience des cliniciens en matière d'accès dans leur province. Les critères de couverture des médicaments publics et les processus de demande pourraient avoir changé depuis que cette analyse a été effectuée. Conclusion: Bien que les patients de la plupart des provinces aient des besoins similaires et que les néphrologues aient des habitudes de prescription similaires, des lacunes subsistent en ce qui concerne le financement public des médicaments pour traiter la GN. Les différences interprovinciales entre les médicaments financés, les critères de financement et le processus de demande peuvent avoir une incidence sur l'accès opportun et équitable aux médicaments pour traiter la GN à travers le Canada. Étant donné la rareté de cette maladie, une approche de financement pancanadienne pourrait être justifiée afin d'améliorer l'état actuel.

Iron replacement and supplementation in patients with chronic kidney disease.

Interest in optimizing iron management in the treatment of anemia of CKD is growing due to concerns that high doses of ESAs may have deleterious effects and the high cost of ESAs in comparison to iron therapy. International guidelines have defined iron targets for this patient population, but there are some unanswered questions with respect to long-term use of iron, such as the maximum TSAT or ferritin concentration and concerns with oxidative stress. Large head-to-head safety studies of the different i.v. iron preparations have not been performed to date and current safety data rely on small studies and spontaneous adverse event reporting. Interprofessional management of anemia, including iron therapy, has shown beneficial effects and should be encouraged.

Reduced drug costs from switching hemodialysis patients from epoetin alfa in multidose vials to pre-filled syringes.

OBJECTIVE: We sought to evaluate epoetin alfa drug costs in hemodialysis (HD) patients after a province-wide switch from multidose vials (MDV) to prefilled syringes (PFS). METHODS: A retrospective study of epoetin alfa drug costs and estimated doses based on these costs during a six-month period of MDV usage (2007) were compared to a PFS usage period (2008). Data were collected from quarterly counts of HD patients receiving epoetin alfa in the Manitoba Renal Program (MRP) and monthly inventory billing records. RESULTS: 756 patients who received epoetin alfa MDV were compared to 799 patients who received epoetin alfa PFS. Average weekly dose calculated from drug costs was 13,282 units (MDV) versus 11,689 units (PFS). Average weekly costs were $195.71 (MDV) versus $183.23 (PFS). This translated to an estimated $12.48 per patient per week in savings ($518,519 annual savings across the Manitoba Renal Program). CONCLUSION: The switch from epoetin alfa MDV to epoetin alfa PFS realized cost savings, likely as a result of reduced drug wastage.

Pharmacotherapeutic options for the treatment of depression in patients with chronic kidney disease.

Depressive disorders occur in up to one-third of patients with chronic kidney disease CKD). First-line pharmacologic treatments include selective serotonin reuptake inhibitors and second generation agents, such as bupropion, mirtazapine, and venlafaxine. Although very little research has been conducted on the use of antidepressants in CKD, health care providers should be aware of renal dose adjustments for these agents, drug interactions, and potential adverse effects. This article reviews the epidemiology and significance of depression in patients with CKD and discusses drug therapy options for treatment of depression in this patient population.

Are CSN and NKF-K/DOQI mineral metabolism guidelines for hemodialysis patients achievable? Results from a provincial renal program.

BACKGROUND: The calcium, phosphorus, and parathyroid hormone targets recommended by the Canadian Society of Nephrology (CSN) encompass a wider range of values as compared to the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) guidelines. We sought to compare mineral metabolism parameters within the Manitoba Renal Program (MRP) to the CSN and NKF-K/DOQI guidelines. Medication use was also examined. METHODS: All hemodialysis patients in Manitoba were evaluated. Values for serum albumin, phosphorus, calcium, intact parathyroid hormone (PTH) and pertinent medications were collected. RESULTS: Five hundred and forty-six patients were included in the analysis. Fifty-three per cent to 81% of MRP patients met individual CSN targets. However, only 26% of patients achieved all targets, despite high usage of phosphate (85.5% calcium carbonate, 16.1% sevelamer, 1.3% aluminum) and PTH-lowering drug therapies (30.2% calcitriol, 2.7% cinacalcet). CONCLUSION: Only a small proportion of patients were able to achieve all three CSN mineral metabolism targets simultaneously. The majority of outliers presented with hyperphosphatemia or hypoparathyroidism.

Conversion from epoetin alfa to darbepoetin alfa within the Manitoba Renal Program: evaluation of dose ratios.

We sought to describe dose conversion ratios between epoetin alfa and darbepoetin alfa for patients with anemia of chronic kidney disease (CKD) in a large provincial renal program. Hemodialysis (HD), peritoneal dialysis (PD) and pre-dialysis patients with CKD were included. Laboratory parameters and darbepoetin alfa doses were compared to epoetin alfa doses (same route). In 2005, 857 patients received darbepoetin alfa and were compared to 746 patients who received epoetin alfa in 2003-2004. Mean dose conversion ratios were 12,939 IU, 53.1 microg, 244:1 for HD; 9,273 IU, 41.8 microg, 222:1 for PD; and 5,516 IU, 25.2 microg and 219:1 for CKD patients. The mean hemoglobin and iron parameters were within K/DOQI targets on both drugs. Conversion ratios in HD, PD and CKD patients using erythropoietic therapies was greater than 200:1 with both intravenous and subcutaneous dosing. Renal programs across Canada should consider dosage conversion ratios in addition to drug acquisition costs when considering a formulary decision about erythropoiesis stimulating agents.

A Review of Phosphate Binders in Chronic Kidney Disease: Incremental Progress or Just Higher Costs?

As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.

Assessment of a fax document for transfer of medication information to family physicians and community pharmacists caring for hemodialysis outpatients.

BACKGROUND: Studies have clearly identified the outpatient dialysis population as one that is at high risk for drug-related problems. The objective of this study was to evaluate whether a fax document was useful for community pharmacies and family physicians to notify these health care providers that their patient was receiving hemodialysis, to update medication and allergy records, provide dosing information on antibiotics and drugs to avoid, facilitate communication from the hemodialysis unit, and to decide if this was a worthwhile project to continue on an on-going basis. METHODS: Fax documents were sent to community pharmacists and family physicians of 70 hemodialysis patients from two different hemodialysis satellite units. The fax document consisted of a brief cover letter with contact numbers, a copy of the patient's medication and allergy list, a table of appropriate antibiotic doses and medications to avoid in dialysis, and a survey to evaluate this project's usefulness. Fisher's exact test was used to determine whether there were any significant differences between the family physician and community pharmacist responses. RESULTS: The survey response rate was 37%. Ninety-five per cent (20/21) of family physicians and 81% (22/27) of community pharmacists who responded to the survey would use the medication profile to update their records. Ninety-five per cent of family physicians and 93% of community pharmacies thought the fax document was an improvement in communication from the dialysis unit. Ninety per cent of family physicians and 85% of community pharmacies thought that the fax document was a worthwhile project for the dialysis unit to continue. No significant differences were found between family physician and community pharmacist responses. CONCLUSIONS: Implementation of a fax document for the transfer of medication information to family physicians and community pharmacists caring for hemodialysis patients aids in updating medication and allergy profiles, improves communication fom the dialysis unit and is considered a worthwhile project to continue on an ongoing basis.