Brian M. Shepler

Comparison of Sevelamer Hydrochloride and Sevelamer Carbonate: Risk of Metabolic Acidosis and Clinical Implications

Hyperphosphatemia is highly prevalent in patients with chronic kidney disease (CKD), particularly in those with advanced or end‐stage renal disease. Sevelamer hydrochloride is an ion‐exchange resin that reduces serum phosphorus concentrations. The agent also produces favorable lipid profile effects and does not cause hypercalcemia. However, reported drawbacks of this agent are metabolic acidosis, high pill burden, and a relatively low affinity and selectivity for phosphate anions. Sevelamer carbonate is a new buffered formulation that does not increase the risk of metabolic acidosis. To determine the roles of these two agents in the treatment of hyperphosphatemia in patients with CKD, we performed a MEDLINE search (June 1995‐June 2008) focusing on the mechanism of action of resin binding with phosphate and the development of metabolic acidosis. We also reviewed studies that evaluated the effects of sevelamer hydrochloride or sevelamer carbonate on serum bicarbonate concentrations. Several studies in patients with CKD and hyperphosphatemia who received hemodialysis or peritoneal dialysis found decreases in serum bicarbonate concentrations with the use of sevelamer hydrochloride, whereas sevelamer carbonate did not have this negative effect on bicarbonate concentrations. Both drugs appear to be equivalent in their abilities to lower serum phosphorus concentrations. However, as sevelamer carbonate does not decrease serum bicarbonate levels, it may be more appropriate for patients at risk for metabolic acidosis who require phosphate binders that do not contain calcium or aluminum.

Evaluation of morbidity and mortality data related to cardiovascular calcification from calcium-containing phosphate binder use in patients undergoing hemodialysis.

Cardiovascular disease is the leading cause of death among patients with stage 5 chronic kidney disease. Several mechanisms are thought to contribute to vascular calcification and subsequent cardiovascular disease in patients who require hemodialysis. One of these mechanisms is the use of calcium‐containing phosphate binders to treat hyperphosphatemia. Although most phosphate binding occurs in the gastrointestinal tract, some calcium is inevitably absorbed and has the potential to perpetuate the calcium‐phosphorus product and the development of vascular and soft tissue calcification. Some phosphate binders such as sevelamer hydrochloride do not contain calcium and therefore may not carry the same risks. We examined the cardiovascular calcification effect and morbidity and mortality data with calcium‐containing phosphate binders compared with sevelamer hydrochloride when given to patients with stage 5 chronic kidney disease for the treatment of hyperphosphatemia. A literature search using the MEDLINE and PubMed databases identified relevant articles from 1989–2009; nine studies compared vascular calcification between a calcium‐containing phosphate binder and sevelamer hydrochloride. Three mortality studies were also identified. Seven of the nine studies reported a statistically significant increase in vascular calcification in patients taking calcium‐containing phosphate binders as measured by coronary artery calcification scores and aortic calcification scores. In two trials, lower mortality rates were observed in the patients receiving sevelamer hydrochloride compared with calcium‐containing phosphate binders. No significant difference in the mortality rate was observed in the third trial. Based on the current literature, it appears that calcium‐containing phosphate binders promote the progression of vascular calcification to a greater extent than does sevelamer hydrochloride. In addition, some evidence suggests that sevelamer hydrochloride may reduce all‐cause mortality rates in patients undergoing hemodialysis, particularly those aged 65 years or older. Thus, although sevelamer hydrochloride appears to be the more appropriate choice of phosphate binder for patients undergoing hemodialysis in whom cardiovascular calcification is a concern, more clinical trials are needed to further guide practitioners on the selection of phosphate binders.

Update on potential drugs for the treatment of diabetic kidney disease.

BACKGROUND Although controlling hyperglycemia and proteinuria is currently the main focus of diabetic kidney disease management, some existing drugs and other new compounds are being evaluated for their ability to interrupt the disease process. Specifically, drugs that interfere with the formation and action of advanced glycation end products and reduce or inhibit fibrosis of the glomerular structures in the presence of hyperglycemia are just 2 examples. OBJECTIVE The aim is to provide an in-depth review of drugs currently being investigated to treat diabetic kidney disease (DKD) through novel mechanisms of action that interrupt the pathologic process. METHODS A literature search was performed of the search engines PubMed (www.pubmed.gov) and ClinicalTrials.gov (www.clinicaltrials.gov), initially using the broad search terms diabetic nephropathy, diabetic kidney disease, and advanced glycation end products. Limits were set to include only English-language articles and studies performed in human subjects from January 2000. Previous review articles on this subject captured through the initial search also served as a basis for identifying drugs that had been under evaluation. Once a list of drugs and compounds was established, each agent was used as an independent search term through the same search engines listed to capture any new and/or ongoing studies for inclusion in this review. Any trials in DKD patients collected through this process were evaluated in this review including Phase I, II, and III studies. RESULTS Fifteen drugs were identified, and 24 studies were reviewed. Ten drugs have evidence of beneficial effects in treating DKD patients as reported by improvements in glomerular filtration rate, albumin-to-creatinine ratio, proteinuria, or serum creatinine concentrations. Five drugs demonstrated no significant benefit or side-effect profiles that would prohibit their routine use. CONCLUSIONS Pirfenidone, doxycycline, bardoxolone, pentoxifylline, ruboxistaurin, pyridoxamine, paricalcitol, FG-3019, AST-120, and allopurinol have shown beneficial effects in treating patients with DKD through modification of the pathologic mechanisms by which hyperglycemia alters the structure and function of the glomerulus. Further evaluation using well-controlled trials in larger patient populations are needed to confirm these benefits.

Potential New Treatments for Diabetic Kidney Disease

Antifibrotic agents, antioxidant agents, ET-a receptor antagonists, and a few other agents with nonspecific or multifaceted mechanisms of action have been evaluated and progressed to small clinical studies in human subjects. Although there are limited data at the present time, these early evaluations have produced some favorable results that at least warrant further investigation. There is certainly not enough compelling evidence to justify the routine use of any of these products specifically for DKD at the moment; however, more well-controlled and adequately powered studies in several hundred patients will help determine which of these may have a place in the DKD treatment armamentarium of the future.

Cinacalcet: A New Treatment for Secondary Hyperparathyroidism in Patients Receiving Hemodialysis

Cinacalcet is the first calcimimetic drug approved by the United States Food and Drug Administration for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. A literature search, performed by using PubMed and MEDLINE from January 1997–June 2004, identified articles concerning the efficacy and safety of cinacalcet in this patient population. Currently, Vitamin D and its analogs are considered first‐line therapy for secondary hyperparathyroidism. However, use of these agents is often accompanied by an increase in serum calcium and phosphorus concentrations, a problem that often limits their use. Cinacalcets mechanism of action decreases parathyroid hormone, calcium, and phosphorus levels, offering potential advantages over the other treatments for secondary hyperparathyroidism. Additional clinical trials are needed to evaluate the long‐term safety and efficacy of the drug as a first‐line agent.

Cost Savings Associated With Pharmacy Student Interventions During APPEs

Objective. To quantify the impact of pharmacy students’ clinical interventions in terms of number and cost savings throughout advanced pharmacy practice experiences (APPEs) using a Web-based documentation program. Methods. Five hundred eighty doctor of pharmacy (PharmD) students completing ten 4-week APPEs during the final year of the curriculum were asked to document all clinical interventions they made using a Web-based documentation tool. Data were collected over 4 academic years. Results. The total number of interventions made was 59,613, the total dollars saved was

Nicotinic acid and nicotinamide: a review of their use for hyperphosphatemia in dialysis patients.

8,583,681, and the average savings per intervention was

Using institutional track programs and block scheduling to help students prepare for postgraduate residency training

148. The top 3 categories of interventions made by students were identifying dosing issues, conducting chart reviews, and recommending appropriate therapy. The top 3 intervention types made by students that resulted in the most dollars saved per intervention were identifying potential allergic reactions, identifying drug interactions, and resolving contraindications. Conclusions. Pharmacy students made important and cost-effective clinical interventions during their APPEs that resulted in significant savings. Documentation programs can track the number, type, and value of the interventions that pharmacy students are making.

A Review Investigating the Effect of Allopurinol on the Progression of Kidney Disease in Hyperuricemic Patients With Chronic Kidney Disease

Phosphate binders have traditionally been used to treat hyperphosphatemia, a common complication in patients with end stage renal disease (ESRD). New evidence suggests that nicotinic acid and its metabolites may effectively decrease phosphorus absorption in the gastrointestinal tract, thereby reducing serum phosphorus concentrations. We conducted a literature search to identify studies of patients with ESRD on dialysis that evaluated the role of niacin and related compounds in decreasing serum phosphorus levels. We searched PubMed using the search terms niacin, nicotinic acid, niacinamide, nicotinamide and hyperphosphatemia. Limits were set to include only those articles published since 2002, conducted in human subjects, and written in the English language. Review articles captured through this process were mined for references to other primary literature that may not have been returned through the initial search. All studies were included if they met the search criteria and were conducted in patients with ESRD who received either hemodialysis or peritoneal dialysis. To identify current, ongoing studies, another search was conducted through clinicaltrials.gov. Among the seven studies that met our exclusion criteria, three used nicotinic acid as the therapeutic intervention and four used nicotinamide. Both nicotinic acid and nicotinamide were effective in significantly reducing serum phosphorus concentrations in patients with ESRD on either hemodialysis or peritoneal dialysis. Additional, large‐scale studies that assess the appropriate dose as well as long‐term safety and efficacy are recommended before clinicians can confirm their place in therapy.

A Comparative Look at the Safety Profiles of Intravenous Iron Products Used in the Hemodialysis Population

PURPOSE The development and implementation of institutional track programs and block scheduling to help students prepare for postgraduate residency training are described. SUMMARY Institutional track and block scheduling models were implemented into advanced pharmacy practice experience rotations to provide students with several of these experiences at the same practice site. Students at Purdue University College of Pharmacy (PUCOP) and Butler University College of Pharmacy and Health Sciences (BUCOPHS) can apply for an institutional track or block schedule. The application process for the institutional track and block scheduling programs provides students with an opportunity to refine written and oral skills that are necessary for residency applications and interviews, since the process mimics that of the ASHP Resident Matching Program. Students are frequently provided with mentors to assist in the residency or fellowship preparation, curriculum vitae or cover letter design, and career planning. Students at the site may also be paired with pharmacy residents enrolled in blocked rotations to serve as mentors. The top students are matched with a practice site and then assigned to five consecutive patient care rotations. Since 2011, a total of 71 students have participated in institutional tracks at PUCOP or block scheduling at BUCOPHS. Most institutional track students (83%) and block scheduling students (81%) were successful in matching to residency programs or hospital pharmacy positions after graduation. CONCLUSION Block scheduling and institutional track programs were offered to students at two colleges of pharmacy interested in pursuing postgraduate residency training. Most institutional track students and block scheduling students successfully matched to residency programs or hospital pharmacy positions after graduation.