Lori D. Wazny

Sodium thiosulfate, bisphosphonates, and cinacalcet for treatment of calciphylaxis

PURPOSE The use of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of calciphylaxis in adults with chronic kidney disease (CKD) is discussed. SUMMARY Calciphylaxis, generally characterized by extraosseous calcification of soft tissues, typically occurs in patients with stage 4 or 5 CKD. Very little data are available regarding the treatment of calciphylaxis. The role of elevated calcium and phosphate concentrations and hyperparathyroidism as risk factors for calciphylaxis has led clinicians to explore therapies that modify these factors, including sodium thiosulfate, bisphosphonates, and cinacalcet. Sodium thiosulfate has been shown to produce clinical improvement of calciphylaxis lesions. Bisphosphonates have been shown to be effective in animal models of calciphylaxis, and the mechanism of action is believed to be due to inhibition of macrophages and local proinflammatory cytokines and binding to calcified vascular smooth muscle cells to inhibit further arterial calcification. Cinacalcet, a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor on the parathyroid gland to calcium, is believed to decrease serum parathyroid hormone levels and stabilize calcium and phosphate concentrations. Cinacalcet has been associated with improved pain control and ulcer healing. Cases describing the use of combination therapy with cinacalcet and sodium thiosulfate for the treatment of calciphylaxis have been published, but the positive effect on wound healing is difficult to attribute to a single drug. CONCLUSION Evidence for the treatment of calciphylaxis with pharmacotherapeutic interventions is limited to case reports. Further research is necessary to fully describe the optimal use of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of calciphylaxis, including their pharmacokinetics in adults with CKD, optimal dosing strategies, and duration of therapy.

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 guidelines 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.

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

Purpose of reviewPatients 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 findingsPharmacists 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. SummaryOpportunities are growing to include pharmacists as integral members of CKD and dialysis healthcare teams to reduce MRPs, increase medication adherence and improve patient outcomes.

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.

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.

Use of an alteplase algorithm for the management of hemodialysis catheter dysfunction

Hemodialysis (HD) catheter dysfunction compromises HD adequacy and increases the cost of patient care. Repeated administration of alteplase in HD catheters typically produces only short‐term benefits. The purpose of this study was to design, implement, and evaluate the efficacy of an experimental alteplase algorithm to manage HD catheter dysfunction. This was a two‐part prospective nonrandomized study. Baseline data of alteplase use and catheter exchange were collected during part 1 of the study. Part 2 consisted of the alteplase algorithm implementation and repeat collection of catheter data. Rates of alteplase use and catheter exchange per 1000 catheter‐days were the primary and secondary outcomes of the study. One hundred and seventy‐two catheters in 131 patients were followed prospectively during the course of the study. The adjusted relative rate (RR) of alteplase use showed no significant difference between both parts of the study, adjusted RR: 1.10, 95% confidence interval (CI) (0.73–1.65). Similarly, catheter exchange rates were not significantly different over the duration of the study (1.12 vs. 1.03 per 1000 catheter‐days). However, waiting time for catheter exchange increased from 20.36 ± 14 days in part 1 to 38.42 ± 28 days in part 2 (P < 0.05). The alteplase algorithm did not significantly reduce alteplase use. This may be partially explained by repeated use of alteplase in part 2, due to longer waiting times for catheter exchange procedures.