Nancy A. Mason

Parenteral iron use in the management of anemia in end-stage renal disease patients

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Data from the Dialysis Outcomes and Practice Patterns Study validate an association between high intravenous iron doses and mortality

Intravenous (IV) iron is required for optimal management of anemia in the majority of hemodialysis (HD) patients. While IV iron prescription has increased over time, the best dosing strategy is unknown and any effect of IV iron on survival is unclear. Here we used adjusted Cox regression to analyze associations between IV iron dose and clinical outcomes in 32,435 HD patients in 12 countries from 2002 to 2011 in the Dialysis Outcomes and Practice Patterns Study. The primary exposure was total prescribed IV iron dose over the first 4 months in the study, expressed as an average dose/month. Compared with 100-199 mg/month (the most common dose range), case-mix-adjusted mortality was similar for the 0, 1-99, and 200-299 mg/month categories but significantly higher for the 300-399 mg/month (HR of 1.13, 95% CI of 1.00-1.27) and 400 mg/month or more (HR of 1.18, 95% CI of 1.07-1.30) groups. Convergent validity was proved by an instrumental variable analysis, using HD facility as the instrument, and by an analysis expressing IV iron dose/kg body weight. Associations with cause-specific mortality (cardiovascular, infectious, and other) were generally similar to those for all-cause mortality. The hospitalization risk was elevated among patients receiving 300 mg/month or more compared with 100-199 mg/month (HR of 1.12, 95% CI of 1.07-1.18). In light of these associations, a well-powered clinical trial to evaluate the safety of different IV iron-dosing strategies in HD patients is urgently needed.

Prescription of antihypertensive agents to haemodialysis patients: time trends and associations with patient characteristics, country and survival in the DOPPS

BACKGROUND Haemodialysis patients were studied in 12 countries to identify practice patterns of prescription of antihypertensive agents (AHA) associated with survival. METHODS The sample included 28 513 patients enrolled in DOPPS I and II. The classes of AHA studied were beta blocker (BB), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), peripheral blocker, central antagonist, vasodilator, long-acting dihydropyridine calcium channel blocker (CCB), short-acting dihydropyridine CCB and non-dihydropyridine CCB. To reduce bias due to unmeasured confounders, the associations with mortality were assessed by separate Cox models based on patient-level prescription and facility prescription practice. RESULTS An increase in prescription of ARBs (9.5%) and BBs (9.1%) was observed from DOPPS I to II. Prescription of AHA classes varied significantly by country, ranging for BBs from 9.7% in Japan to 52.7% in Sweden and for ARBs from 5.5% in Italy to 21.3% in Japan in DOPPS II. Facilities that treated 10% more patients with ARBs had, on average, 7% lower all-cause mortality, independent of patient characteristics and the prescription patterns of other antihypertensive medications (P = 0.05). Significant and independent associations with reduction in cardiovascular mortality were observed for ARBs (RR = 0.79; P = 0.005) and BBs (RR = 0.87, P = 0.004) in analyses of patient-level prescriptions. These associations in the facility-level model followed the same direction. CONCLUSIONS DOPPS data show large variations across countries in AHA prescription for haemodialysis patients. The data suggest an association between ARB use and reduction in all-cause mortality, as well as with the use of BBs and reduction in cardiovascular mortality among haemodialysis patients.

Variation in intravenous iron use internationally and over time: the Dialysis Outcomes and Practice Patterns Study (DOPPS)

BACKGROUND To examine patterns of intravenous (IV) iron use across 12 countries from 1999 to 2011. METHODS Trends in iron use are described among 32 192 hemodialysis (HD) patients in the Dialysis Outcomes and Practice Patterns Study. Adjusted associations of IV iron dose with serum ferritin and transferrin saturation (TSAT) values were also studied. RESULTS IV iron was administered to 50% of patients over 4 months in 1999, increasing to 71% during 2009-11, with increasing use in most countries. Among patients receiving IV iron, the mean monthly dose increased from 232 ± 167 to 281 ± 211 mg. Most countries used 3 to 4 doses/month, but Canada used about 2 doses/month, Italy increased from 3 to almost 6 doses/month and Germany used 5 to 6 doses/month. The USA and most European countries predominantly used iron sucrose and sodium ferric gluconate. A significant use of iron dextran was limited to Canada and France; iron polymaltose was used in Australia and New Zealand; and Japan used ferric oxide saccharate, chondroitin polysulfate iron complex and cideferron. Ferritin values rose in most countries: 22% of patients had ≥ 800 ng/mL in the recent years of study. TSAT levels increased to a lesser degree over time. Japan had much lower IV iron dosing and ferritin levels, but similar TSAT levels. In adjusted analyses, serum ferritin and TSAT levels increased signifcantly by 14 ng/mL and 0.16%, respectively, for every 100 mg/month higher mean monthly iron dose. CONCLUSIONS IV iron prescription patterns varied between countries and changed over time from 1999 to 2011. IV iron use and dose increased in most countries, with notable increases in ferritin but not TSAT levels. With rising cumulative IV iron doses, studies of the effects of changing IV iron dosing and other anemia management practices on clinical outcomes should be a high priority.

Polypharmacy and medication-related complications in the chronic kidney disease patient.

Purpose of reviewMedication-related problems are very common in patients with chronic kidney disease (CKD). Identification, prevention and management of these problems require a comprehensive, interdisciplinary approach. This article reviews the recent literature regarding medication-related problems in CKD and proposes initiatives for addressing these problems through a structured review process and use of patient-centered adherence-promoting strategies. Recent findingsPharmacist-conducted medication review and intervention programs are successful at identifying and resolving medication-related problems in CKD patients. These programs are associated with a reduction in the number of medications and frequency of hospitalization, and are associated with maintenance of quality of life. However, adherence continues to be a major medication-related problem in CKD care. SummaryStructured medication review and assessment of adherence assist in identification and resolution of medication-related problems in CKD. More research is needed on successful methods to improve medication adherence and related health outcomes.

An Advanced Pharmacy Practice Experience in Transitional Care

Objectives. To implement and assess a 4-week advanced pharmacy practice experience in transitional care. Design. Students participated in the transitional care planning of patients being discharged from 4 general medicine services. Students interviewed patients; assessed discharge medications; reconciled preadmission and discharge medications; provided medication counseling; and conducted postdischarge follow-up by phone to assist patients with medication-related problems and identify additional concerns. Assessment. Student involvement increased the number of patients who could be assessed and interviewed by the pharmacist preceptor from 10 patients/day to 15 to 20 patients/day. Students strengthened their provider-patient and provider-provider communication skills and developed skills in identifying and resolving barriers to medication adherence. Conclusion. This transitional care APPE provided students an opportunity to gain experience and self-confidence in the application of pharmaceutical care skills in a transitional care setting, while also providing valuable patient care services to the hospital.

Comparison of 3 vancomycin dosage regimens during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration.

AIMS Traditionally, vancomycin is administered following dialysis to minimize drug loss when high-flux membranes are employed. Unfortunately, this approach is extremely inconvenient for patients and staff, requiring the patients to remain in the unit for at least 1 hour following dialysis. This study was designed to evaluate the feasibility of administering vancomycin during hemodialysis. Specifically, this study was designed to compare the pharmacokinetics of vancomycin when administered during the last 1-2 hours of dialysis (i.e. intra-dialytic administration) to that administered after completion of dialysis. MATERIALS AND METHODS In a randomized, 3-way crossover trial, the pharmacokinetics of vancomycin were evaluated in 9 hemodialysis patients, comparing vancomycin 15 mg/kg following dialysis (Phase I), vancomycin 15 mg/kg during the last hour of hemodialysis (Phase II) or vancomycin 30 mg/kg during the last 2 hours of hemodialysis (Phase III). Vancomycin plasma concentrations were obtained over an 8-day period and subsequent comparisons between the treatment approaches were made with paired t-tests or ANOVA, as appropriate. Dialysate vancomycin concentrations determined on Day 1 and Day 3 of Phases II and III were used to calculate the fraction of vancomycin dose removed, and were compared to plasma data using paired t-tests. RESULTS Vancomycin was significantly removed (33.4 to 39.5%) during a 3- to 4-hour high-flux dialysis session occurring on Day 3 after vancomycin administration. Mean serum concentrations immediately following intradialytic vancomycin administration of 15 mg/kg over the last hour of dialysis or 30 mg/kg over the last 2 hours of dialysis were initially high (77.7 and 95.5 mcg/ml respectively), but fell to 25.9 and 40.5 mcg/ml, respectively, by 4 hours post-dialysis. Predialysis concentrations on Days 3, 5 and 8 were similar for vancomycin 30 mg/kg administered over the last 2 hours of dialysis as compared with a 15 mg/kg dose given after dialysis. Vancomycin 15 mg/kg over the last hour of dialysis resulted in significantly lower subsequent predialysis concentrations than the other dosing schemes. CONCLUSIONS Vancomycin administration of 30 mg/kg over the last 2 hours of dialysis achieves serum concentrations similar to conventional dosing of 15 mg/kg after dialysis and would allow dosing on a weekly basis.

Angiotensin-Converting Enzyme Inhibitors and Renal Function

The effects of angiotensin-converting enzyme (ACE) inhibitors on renal hemodynamics vary widely depending on the preexisting physiologic and pathologic state of the kidneys. Although some studies of ACE inhibitors in primary essential hypertension have demonstrated increases in glomerular filtration rate (GFR) and effective renal plasma flow in patients with renal impairment, other studies have not shown these same beneficial results. The difference may involve the choice of ACE inhibitor used in the investigations, but controlled comparison trials are needed to determine whether this is the case. The use of ACE inhibitors in renovascular hypertension remains controversial. ACE inhibition can interfere with the autoregulation of GFR mediated by angiotensin II and may lead to deterioration of renal function, especially in patients with bilateral renal artery stenosis or stenosis of a solitary kidney. Additionally, ACE inhibitors have been shown to cause a decline in GFR in the kidney affected by the stenosis, whether or not clinically apparent renal insufficiency occurs. Although the functional impairment associated with ACE inhibitors in renal artery stenosis has generally been reversible following removal of the drug, the consequences of a long-term reduction in GFR are unknown. Treatment of stable congestive heart failure (CHF) with ACE inhibitors can result in enhancement of GFR and reduction of sodium and fluid retention, thus improving the clinical state. However, in patients with decompensated cardiac failure, renal perfusion pressures may already be at or near the autoregulatory breakpoint and ACE inhibition may cause deterioration of renal function. In general, ACE inhibitors can be used safely in CHF if they are initiated cautiously, with adjustment of ACE inhibitor and diuretic dosages to avoid systemic hypotension and sodium and fluid depletion. In studies comparing the agents, enalapril and lisinopril have both been shown to cause higher incidences of renal function deterioration than has captopril. These findings suggest that the more complete or sustained ACE inhibition seen with the longer-acting agents may be detrimental to renal function in patients with CHF. The use of ACE inhibitors in the treatment of proteinuria is the newest area of research with these agents. At present it appears that ACE inhibitors reduce urinary protein excretion the most effectively in diabetic patients with mild proteinuria and in hypertensive patients with renal insufficiency and proteinuria due to glomerular disorders. More study is needed to determine whether these agents can reduce the rate of renal failure progression and to define the patient populations expected to benefit most. ACE inhibitors can also cause renal toxicity in the form of proteinuria or renal insufficiency. In general, these adverse effects are rare. Because these agents are eliminated renally, initial dosages should be reduced in renal failure. Because all three ACE inhibitors are substantially removed by hemodialysis, supplemental doses are recommended if blood pressure allows.

Strategies for reducing polypharmacy and other medication-related problems in chronic kidney disease.

Medication‐related problems are very common in patients with chronic kidney disease (CKD). These problems are often avoidable and can result in detrimental patient consequences and high financial costs. Despite these risks, it is often medically necessary to prescribe multiple medications to treat the comorbid conditions that accompany CKD. In addition, patients’ use of nonprescription medications and changes in pharmacokinetic and pharmacodynamic parameters may further contribute to medication‐related problems in CKD, including drug interactions and the need for dosage adjustments. A structured medication assessment process is one approach to reducing the risks associated with medication‐related problems. This multifaceted process involves a comprehensive medication history interview, structured therapy assessment, and open communication between members of the medical team. A detailed description of this process is provided to aid healthcare providers in addressing this important issue.

Improving student education and patient care through an innovative introductory pharmacy practice experience

![Figure][1] The standards of the Accreditation Council for Pharmacy Education (ACPE) for doctor of pharmacy programs require pharmacy curricula to provide students with introductory pharmacy practice experiences (IPPEs), which are defined as “practice experiences offered in various