Naomi V. Dahl

Ferric Gluconate Reduces Epoetin Requirements in Hemodialysis Patients with Elevated Ferritin

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

Oxybutynin transdermal system improves the quality of life in adults with overactive bladder: a multicentre, community-based, randomized study

To assess health‐related quality‐of‐life (HRQoL) and safety with the oxybutynin transdermal system (OXY‐TDS) (Oxytrol®, Watson Pharma, Corona, CA, USA) in the Multicentre Assessment of Transdermal Therapy in Overactive Bladder With Oxybutynin (MATRIX) study, as HRQoL measurements are increasingly important in evaluating pharmacotherapy for overactive bladder (OAB).

Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Alternative Medicine and Nephrology Series Editor: Naomi V. Dahl: Herbs and Supplements in Dialysis Patients: Panacea or Poison?

The safety of herbal remedies and supplement use is of particular concern in patients with renal disease, and reliable information is not always easy to find. Predialysis patients may be drawn to complementary and alternative medicine (CAM) because they believe it can help prevent the progression of their renal disease. The purpose of this series of articles on alternative medicine for nephrologists is to address concerns and issues specific to CAM use in dialysis patients and to provide a guide to reliable sources of information. This introductory article emphasizes safety issues with a focus primarily on herbal medicine. Lack of regulation means that patients may not actually be taking what they think they are. Independent laboratory analyses have shown a lack of stated label ingredients and many instances of supplements and traditional remedies being contaminated with pesticides, poisonous plants, heavy metals, or conventional drugs. While certain supplements are always unsafe (carcinogenic, hepatotoxic, glandular extracts), others are specifically contraindicated in renal disease. Supplement use may be especially hazardous in renal disease because of unpredictable pharmacokinetics, drug interactions, negative effects on kidney function, nephrotoxicity, hemodynamic alterations, unpredictable effects on blood pressure or blood glucose, or potentiation of electrolyte abnormalities. There are no data on potential dialyzability of either active compounds, or their potentially active or toxic metabolites. Many supplements contain metal ions and other minerals. Transplant recipients are also at risk from potential unpredictable effects on immune function. Recommendations and information resources are listed.

Thrombosis with erythropoietic stimulating agents-does iron-deficient erythropoiesis play a role?

Thrombocytosis is common in iron deficiency and resolves following iron repletion. Increased platelet number, whether from iron deficiency or from other causes, may increase the risk of thrombovascular events. One mechanism thought to mediate iron deficiency‐induced thrombocytosis is increased erythropoietin production. Similarly, erythropoietic stimulating agents (ESA) have long been known to increase platelet number and frequently lead to functional or absolute iron deficiency. This state of relative or absolute iron deficiency may be the mechanism whereby ESA increase the platelet count. If correct, co‐administration of iron should prevent or diminish ESA‐driven thrombocytosis. Data from the DRIVE trial in hemodialysis patients do, in fact, suggest that this is the case. Platelet counts in patients receiving IV iron decreased, while they remained unchanged in patients not given iron (mean change −29,000/μl vs. −0/μl; p = 0.017). Other supporting data have been observed in IV iron trials in oncology patients. The harm from higher hemoglobin targets and higher ESA doses may be mediated in part through induction of iron deficiency and thrombocytosis. The major anemia trials of ESAs have not reported platelet data, but should examine the relationship of platelet count, iron deficiency, IV iron administration, and cardiovascular events in greater detail.

Effects of oxybutynin transdermal system on health-related quality of life and safety in men with overactive bladder and prostate conditions

Aims:  Overactive bladder (OAB) is common in men and may exist concomitantly with benign prostatic hyperplasia (BPH) and obstruction. We present a subanalysis of results from men with OAB in a 6‐month, open‐label study of treatment with the oxybutynin transdermal system (OXY‐TDS). Broad entry criteria were incorporated to yield a clinically representative population.

Proteinuria induced by parenteral iron in chronic kidney disease--a comparative randomized controlled trial.

BACKGROUND AND OBJECTIVES Among patients with chronic kidney disease (CKD), differences in proteinuria are seen between intravenous iron preparations after a single dose exposure. This study examined differences in proteinuria between two intravenous iron preparations after multiple doses. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients with iron-deficiency anemia and CKD, stratified by angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor-blocker (ARB) use, were randomized to iron sucrose or ferric gluconate. Each patient at 12 centers received 100 mg of study drug weekly for 5 weeks. Urine protein/urine creatinine ratio was measured before each dose and frequently thereafter for 3 hours. RESULTS Postbaseline data were available from 33 patients receiving iron sucrose and 29 patients receiving ferric gluconate. Although neither preparation of intravenous iron increased the predose level of proteinuria, the proteinuric response to intravenous iron was dependent on the type of iron and ACEI/ARB use. Without ACEIs/ARBs, ferric gluconate tended to cause less proteinuria with repeated iron administration; iron sucrose did not mitigate or aggravate proteinuria. Among patients receiving ACEIs/ARBs, in contrast to ferric gluconate, which produced only mild transient proteinuria, iron sucrose produced a consistent and persistent proteinuric response that was on average 78% greater. CONCLUSIONS Although multiple doses of either intravenous iron did not increase basal levels of proteinuria, postdose proteinuria was greater with iron sucrose than with ferric gluconate. These data suggest that nephrotoxicity of iron may depend on type of intravenous iron and on ACEI/ARB use. The long-term effects on kidney function need to be further evaluated.

Single-Dose Pharmacokinetics of Sodium Ferric Gluconate Complex in Iron-Deficient Subjects

Study Objectives. To determine the single‐dose pharmacokinetics of intravenous sodium ferric gluconate complex in sucrose injection (SFGC) in iron‐deficient human volunteers, and to assess iron transport.

Editorial Focus: Thrombosis with Erythropoietic Stimulating Agents—Does Iron‐Deficient Erythropoiesis Play a Role?

Thrombocytosis is common in iron deficiency and resolves following iron repletion. Increased platelet number, whether from iron deficiency or from other causes, may increase the risk of thrombovascular events. One mechanism thought to mediate iron deficiency‐induced thrombocytosis is increased erythropoietin production. Similarly, erythropoietic stimulating agents (ESA) have long been known to increase platelet number and frequently lead to functional or absolute iron deficiency. This state of relative or absolute iron deficiency may be the mechanism whereby ESA increase the platelet count. If correct, co‐administration of iron should prevent or diminish ESA‐driven thrombocytosis. Data from the DRIVE trial in hemodialysis patients do, in fact, suggest that this is the case. Platelet counts in patients receiving IV iron decreased, while they remained unchanged in patients not given iron (mean change −29,000/μl vs. −0/μl; p = 0.017). Other supporting data have been observed in IV iron trials in oncology patients. The harm from higher hemoglobin targets and higher ESA doses may be mediated in part through induction of iron deficiency and thrombocytosis. The major anemia trials of ESAs have not reported platelet data, but should examine the relationship of platelet count, iron deficiency, IV iron administration, and cardiovascular events in greater detail.

Impact of transdermal oxybutynin on work productivity in patients with overactive bladder: results from the MATRIX study.

AbstractBackground: Overactive bladder syndrome (OAB) is a common condition affecting a significant number of working adults, resulting in increased healthcare utilization, reduced quality of life and decreased work productivity. The MATRIX study was a large, prospective, community-based, observational US study aimed at evaluating the impact of oxybutynin transdermal system (OXY-TDS). In this paper, we report on productivity findings among working adults in MATRIX. Methods: This study enrolled 2878 adults (aged ≥18 years) with symptoms of OAB from 327 practice sites throughout the US. All subjects received OXY-TDS (3.9 mg/day up to 6 months). Baseline versus end-of-study productivity was measured using the Work Productivity Questionnaire (WPQ). The WPQ includes a subset of questions from the Work Limitations Questionnaire (WLQ) and consists of four scales: (i) physical; (ii) time management; (iii) mental; and (iv) output demands. Overall productivity was measured by the work productivity index score (WPQ Index; a summary score based on scales) and work productivity loss score (WPLS; a measure of reduced output compared with healthy workers). Psychometric performance of the WPQ instrument is also reported, since this study represents the first use of the tool. Results: Of the participants, 52% were of working age (18–65 years) and 38.6% were employed. A total of 1112 working adults participated in MATRIX and were included in this analysis. They had a mean age of 52.4 years; 92.2% were female and 80.9% were Caucasian. Subjects who reported that they were most affected by OAB were also most impaired at work. After OXY-TDS treatment, participants experienced significant improvements in mean scores for all four WPQ scales (p ≤0.0002) and the mean WPQ Index decreased from 8.2 to 5.5 (p < 0.0001). In addition, the WPLS decreased from 7.7% to 5.2% (p < 0.0001), indicating improvement in work function with OXY-TDS treatment. Conclusion: OAB contributes to decreased work productivity due to job interruptions as well as fatigue. OXY-TDS may result in productivity improvement when patients receive 3.9 mg/day via twice weekly patch application for up to 6 months.