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Biomedical subjects

Steven Fishbane

Publications and source records attributed to Steven Fishbane.

At least 19 recordsLinked to original sources
PubMed2006

What is needed to achieve a hemoglobin of 11.0-13.0 g/dl in end-stage renal disease.

Effective treatment of anemia in end-stage renal disease (ESRD) results in reduced fatigue and improved quality of life. The National Kidney Foundation's 2006 anemia treatment guidelines recommend maintaining hemoglobin (Hb) at >11 g/dl, while noting that there is insufficient evidence to routinely maintain Hb levels > or =13.0 g/dl. Success in achieving Hb levels within these targets requires careful monitoring and adjustments to treatment. In addition, causes for diminished response and refractory anemia must be adequately evaluated. In this article, factors important for achieving Hb 11-13 g/dl in patients with ESRD are reviewed.

Anemia↗
PubMed2006

Iron supplementation in renal anemia.

Iron-deficiency frequently develops in patients with chronic kidney disease who are treated with recombinant human erythropoietin (rHuEPO). It results in reduced effectiveness of anemia therapy; patients may fail to reach hemoglobin targets or may require excessively large doses of rHuEPO. It has been recognized widely that iron management, monitoring for iron deficiency, and effective iron supplementation forms a core component of anemia therapy. This review discusses the physiology of iron balance, derangements in iron balance in chronic kidney disease (CKD), and the diagnosis and treatment of iron deficiency in patients treated with rHuEPO.

Anemia↗
PubMed2006

Drug insight: Safety of intravenous iron supplementation with sodium ferric gluconate complex.

Intravenous iron is necessary for optimal management of anemia in patients receiving hemodialysis and is utilized in the majority of these patients in the US. The availability of nondextran formulations of intravenous iron has significantly improved the safety of its use. The nondextran iron formulation sodium ferric gluconate complex (SFGC) has been extensively studied in the hemodialysis population, with two large phase IV trials documenting its safety. SFGC is efficacious and, at recommended doses, is associated with a low incidence of adverse events. There have been few comparative studies of the nondextran intravenous iron preparations; however, they are known to have different pharmacokinetic characteristics. There is also evidence to indicate that these compounds differ in terms of their cytotoxic and proinflammatory properties, and their propensity to induce oxidative stress. This paper reviews the current literature on the safety of SFGC and examines the emerging safety issues surrounding the use of intravenous iron.

Ferric Compounds↗
PubMed2005

The effect of a change in epoetin alfa reimbursement policy on anemia outcomes in hemodialysis patients.

In 1997, the Health Care Financing Administration Hematocrit Measurement Audit (HMA) program initiated use of a 3-month rolling average hematocrit (Hct) level for reimbursement of epoetin claims in hemodialysis patients, with denial of payment when this value exceeded 36.5%. This study evaluated the impact of the HMA program on anemia-related outcomes in hemodialysis patients. An observational, retrospective study of 987 hemodialysis patients from 11 dialysis centers in the United States was performed, collecting data between October 1996 and December 1997. Centers were selected from a pool of nearly all facilities in the United States, which during May 1997 satisfied one of two criteria: greater than 75% of patients at the facility had mean Hct level of > or =33% (Group A) or fewer than 50% of patients at the facility had mean Hct level of > or =33% (Group B). Each facility maintained its own anemia management practices without specific anemia management interventions as part of this study. Hct level, hemoglobin (Hb) level, and epoetin dose were analyzed to compare the pre-HMA period (October 1996 to May 1997) to the HMA period (June to December 1997) and/or for each of the five quarters of the study period. The primary study endpoint was the percentage of patients with Hct levels of > or =33% during each study quarter. The mean Hct level at baseline was 34% in Group A and 33.4% in Group B (p = 0.01). Hct levels, which were increasing before implementation of the HMA program, decreased during the HMA period (p < 0.001 and p = 0.013 in Groups A and B, respectively). The percentage of patients in Groups A and B with mean quarterly Hct levels of > or =33% decreased during the last quarter of the HMA implementation period compared to the quarter immediately preceding the start of the HMA program (p < 0.001 for both comparisons). Changes in Hb levels were similar to those seen in Hct levels. The mean epoetin dose administered decreased from 13,090 U/week at the start of the study to 11,884 U/week immediately before the HMA program took effect (p < 0.05). The HMA program adversely affected anemia treatment outcomes, regardless of whether dialysis units before HMA implementation had <50% of patients with a Hct level of > or =33% or had >75% of patients with a Hct level of > or =33%. The decline in mean weekly dose of epoetin was likely a result of withholding doses out of concern among providers about risk of reimbursement denial.

Adult↗
PubMed2005

Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin.

BACKGROUND: Treatment with recombinant human erythropoietin (rHuEPO) has been a major advance for the management of anemia in patients on hemodialysis. Therapy, however, is often observed to be associated with recurrent cyclic fluctuations in hemoglobin levels. The purpose of this analysis was to describe the phenomenology of hemoglobin cycling during rHuEPO treatment. METHODS: Data were analyzed for 281 hemodialysis patients treated at Winthrop-University Hospital Dialysis Centers between 1998 and 2003. Eligible patients' first full 1-year period with less than 10 hospital days was studied. Hemoglobin cycling (cycles with amplitude >1.5 g/dL and duration >8 weeks) and excursions (half of one full cycle) were analyzed. RESULTS: Greater than 90% of patients experienced hemoglobin cycling. The mean number of hemoglobin excursions was 3.1 +/- 1.1 per patient/year. The mean amplitude per hemoglobin excursion was 2.51 +/- 0.89 g/dL. The mean duration of hemoglobin excursions was 10.3 +/- 5.1 weeks. Factors associated with initiation of up excursions included increases in rHuEPO dose (84%), intravenous iron treatment initiation or increase in dose (27%), posthospital discharge (36%), factors associated with down excursions included rHuEPO dose hold (15%) or dose reduction (62%), infection (6%), discontinuation of intravenous iron therapy (5%), and hospitalization (14%). Patients with frequent hemoglobin cycling (>two full cycles per year) were characterized as being more responsive to rHuEPO [index of EPO responsiveness (ERI) 1036 +/- 659 compared to 1992 +/- 701 for other patients] (P = 0.02). CONCLUSION: Hemoglobin cycling is a common occurrence in rHuEPO-treated hemodialysis patients. It is most closely associated with frequent rHuEPO dose changes, hospitalization, and iron treatment practices.

Aged↗
PubMed2004

N-acetylcysteine in the prevention of radiocontrast-induced nephropathy.

N-acetylcysteine is a remarkably active agent shown to be useful in a variety of clinical settings. The drug has actions relevant to radiocontrast-induced nephropathy (RCIN) that include vasodilatation, enhancement of renal medullary blood flow, and antioxidant properties. The drug's pharmacokinetics are remarkable for almost complete first pass metabolism after oral administration, resulting in no free drug reaching the circulation. After intravenous administration, extensive reaction with tissue and plasma proteins greatly limits the amount of circulating free drug. Given the difficulty achieving free drug in the systemic circulation, it is highly likely that the drug works via its metabolites. The primary mechanism may be through L-cysteine as a cellular source for glutathione production. Clinical studies of N-acetylcysteine in the prevention of RCIN have yielded highly mixed results; five were dramatically positive, and eight others had no demonstrable efficacy at all. The following will review the individual studies, attempt to reconcile the divergent results, and propose future research needs.

Acetylcysteine↗
PubMed2004

Cytoprotection by darbepoetin/epoetin alfa in pig tubular and mouse mesangial cells.

BACKGROUND: Erythropoietin has recently been found to have cytoprotective effects in the central nervous system (CNS) and retina. The purpose of this study was to determine if darbepoetin alfa (DA) has cytoprotective properties in renal tissues. METHODS: DA was studied in LLC/PK1 and mesangial cells. Renal cellular injury was induced in different experiments by prostaglandin D2 synthase (PGDS), camptothecin, hydrogen peroxide, and hypoxia. Cellular proliferation and apoptosis were measured [apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay or by caspase-3 activity]. In a separate experiment, an inactive form of erythropoietin alfa was used to study receptor effects. RESULTS: DA protected against the antiproliferative effects of PGDS. In both LLC/PK1 (TUNEL and caspase-3) and mesangial cells (TUNEL), DA reduced the apoptotic stimulus of PGDS. Epoetin alfa was also found to reduce apoptosis. In LLC/PK1 cells, DA reduced apoptosis induced by camptothecin, but not hydrogen peroxide. DA reduced LLC/PK1 apoptosis induced by hypoxia when added 24 hours before hypoxia, but not when given concurrent with the hypoxic stimulus. Erythropoietin inactive did not protect against PGDS-induced apoptosis. CONCLUSION: DA has renal antiapoptotic effects for both toxic and hypoxic stimuli. The effect may be mediated via the Erythropoietin receptor.

Animals↗
PubMed2003

Safety in iron management.

Intravenous (IV) iron therapy has become an integral part of hemodialysis management during the past several decades, and the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative guidelines recognize that most patients undergoing hemodialysis will require IV iron therapy on a regular basis to reach target hemoglobin (Hgb) levels. There now are three IV iron compounds available in the United States: iron dextran, sodium ferric gluconate, and iron sucrose. Although all have been proven effective for increasing Hgb/hematocrit levels, recent data show differences in their relative safety profiles. During the past two decades, more than 30 deaths have been attributed to the use of IV iron dextran. The two newer compounds available in the United States, sodium ferric gluconate and iron sucrose, have more favorable safety profiles, with the largest prospective safety comparison to date showing sodium ferric gluconate to be similar to placebo in the incidence of serious anaphylactoid-type reactions. This article reviews safety data surrounding the IV iron therapies.

Anaphylaxis↗
PubMed2003

Hemoglobin variability in epoetin-treated hemodialysis patients.

BACKGROUND: Understanding the clinical variability of hemoglobin measurements in epoetin-treated hemodialysis patients is important, particularly when this therapy is aimed at maintaining patient hemoglobin levels within a narrow range, such as the 11 to 12 g/dL range recommended in National Kidney Foundation Kidney Dialysis Outcomes Quality Initiative (NKF-K/DOQI) guidelines. This study examines hemoglobin variability under conditions of standard clinical practice in epoetin-treated hemodialysis patients. METHODS: We studied 987 hemodialysis patients participating in an observational retrospective study that evaluated anemia management practices from October 1, 1996 to December 31, 1997 at 11 United States dialysis centers that were randomly selected from a pool of nearly all United States dialysis facilities. Each participating facility maintained its own anemia management protocols without specific anemia management recommendations or interventions made as part of this study. Hemoglobin variability was determined by calculating the 1-month and 2- to 6-month rolling average hemoglobin for each patient. The range of mean hemoglobin values that included the middle 50% (25th to 75th percentile), 80% (10th to 90th percentile), and 90% (5th to 95th percentile) of values were determined. The hemoglobin ranges that included 1 standard deviation (SD) (67%) of the study values and 2 SD (95%) of the study values for each time period were calculated. RESULTS: The mean hemoglobin was between 10.9 and 11.2 g/dL throughout the study. The hemoglobin range encompassing 50%, 80%, and 90% of values from a single month was 1.7, 3.3, and 4.4 g/dL, respectively. A progressive narrowing in the range of hemoglobin values encompassed by each percentile grouping (i.e., hemoglobin variability) was observed as longer rolling intervals were averaged. The hemoglobin range within the 25th to 75th percentile was 1.7 g/dL using single-month hemoglobin values and 1.1 g/dL using a 6-month rolling average. The range of hemoglobin values that encompassed 90% of patients was 4.4 g/dL using single-month values, 3.7 g/dL using 3-month rolling averages, and 3.2 g/dL using 6-month rolling averages. Fewer than 50% of patients had hemoglobin values within the 1.0 g/dL NKF-K/DOQI recommended range, even when a 6-month rolling average was applied. When hemoglobin values were measured for 1 month, 1 SD was 1.4 g/dL; for the 3-month rolling average, 1 SD was 1.1 g/dL; and for the 4-, 5-, and 6-month rolling averages, 1 SD was 1.0 g/dL. Greater hemoglobin variability correlated with higher mean corpuscular hemoglobin (P = 0.003) and serum ferritin (P = 0.047), and inversely correlated with age (P = 0.006) and serum albumin (P = 0.0001). CONCLUSION: Substantial variability occurs in hemoglobin values in epoetin-treated hemodialysis patients. The NKF-K/DOQI recommended hemoglobin range appears to be too narrow in clinical practice. Expanding the target range and use of rolling average hemoglobin intervals of 3 to 6 months as a clinical and quality assurance measure avoids clinical variability inherent with the use of isolated hemoglobin values or single-month hemoglobin averages.

Aged↗
PubMed2003

Sodium ferric gluconate complex in hemodialysis patients. II. Adverse reactions in iron dextran-sensitive and dextran-tolerant patients.

BACKGROUND: Iron dextran administration is associated with a high incidence of adverse reactions including anaphylaxis and death. Although dextran, rather than iron, is believed to be the cause of these reactions, it is not known whether iron dextran-sensitive patients can be safely administered another form of parenteral iron, sodium ferric gluconate in sucrose (SFGC). METHODS: In a 69 center, prospective, double-blind, controlled trial of safety and tolerability of SFGC, the rate of reactions to SFGC and placebo in 144 iron dextran-sensitive patients was compared with 2194 patients who were previously tolerant to iron dextran preparations. Serum tryptase levels, a marker of mast cell degranulation, also were measured. RESULTS: Among 143 iron dextran-sensitive patients exposed to SFGC, three (2.1%) were intolerant. All three had suspected allergic events to SFGC, including one patient with a serious reaction (0.7%). One dextran-sensitive patient (0.7%) had a suspected allergic reaction after placebo. In contrast, among 2194 iron dextran-tolerant patients, reactions to SFGC were significantly less common, with SFGC intolerance seen in seven patients (0.3%; P = 0.020), including five (0.2%) who had suspected allergic events (P = 0.010), but none who had serious events (0.0%; P = 0.061). Two iron dextran-tolerant patients (0.09%) had allergic-like reactions following placebo injections. Two of the three suspected allergic events in the iron dextran-sensitive group were confirmed as mast cell dependent by a 100% increase in serum tryptase, while there were no confirmed allergic events in the iron dextran-tolerant group. Long-term exposure to SFGC in iron dextran-sensitive patients resulted in intolerance in only one additional patient and no serious adverse events. CONCLUSIONS: Patients with a history of iron dextran sensitivity had approximately sevenfold higher rates of reaction to both placebo and SFGC compared to iron dextran tolerant patients. However, logistic regression analysis, performed to account for the higher reaction rate to placebo, suggests that this increased reactivity was not drug-specific nor immunologically mediated, but represented host idiosyncrasy. These results support the conclusions that reactions to SFGC can be attributed to pseudoallergy, and that SFGC is not a true allergen.

Drug Hypersensitivity↗
PubMed2002

Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compared to placebo and iron dextran.

BACKGROUND: Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control. METHODS: This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125 mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo comprising bacteriostatic saline. RESULTS: A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001. CONCLUSION: SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.

Adult↗
PubMed2002

A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography.

BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction after cardiac angiography. Recently, N-acetylcysteine (NAC) has been found to reduce the risk of CN after CT imaging with contrast enhancement. The purpose of the current study was to evaluate the efficacy of NAC for the prevention of CN in the setting of cardiac angiography. METHODS: Eligible patients were those undergoing cardiac angiography with serum creatinine>1.7 mg/dL. Patients were randomized to one of two groups: Group 1, IV hydration and NAC, 1200 mg one hour before angiography, and a second dose 3 hours after; Group 2, IV hydration and placebo. CN was defined as an increase of 0.5 mg/dL in serum creatinine. RESULTS: Seventy-nine patients completed the study. There were no significant differences between the groups in baseline characteristics, duration of angiography, mean volume of dye infused or mean IV hydration. Contrast nephropathy developed in 24.0% of subjects, 26.3% NAC, and 22.0% placebo (P = NS). Among subjects with diabetes mellitus, there was no significant difference in the rate of CN between the groups (42.1% NAC, 27.8% placebo; P = 0.09). The independent predictors of CN risk were diabetes mellitus and preexisting chronic renal insufficiency. CONCLUSIONS: NAC was not effective for the prevention of CN after cardiac angiography.

Acetylcysteine↗
PubMed2002

Occult infection of old nonfunctioning arteriovenous grafts: a novel cause of erythropoietin resistance and chronic inflammation in hemodialysis patients.

BACKGROUND: Occult infection of old nonfunctioning arteriovenous grafts (AVGs) is frequent among hemodialysis patients. It is a recognized cause of bacteremia and other infectious complications. Additionally, old nonfunctioning AVGs may be harbingers of other noninfectious complications. The aim of this study was to investigate whether occult infection of old nonfunctioning AVGs is a cause of a chronic inflammatory state in hemodialysis patients. METHODS: This study was performed in two phases: In the first phase (study 1), 22 patients with clinically proven occult infection of old nonfunctioning AVG were identified, and data on hemoglobin, weekly erythropoietin dose, and albumin levels were collected retrospectively. Comparisons were made between values obtained pre- and post-AVG resection. In the second phase (study 2), we examined whether the presence of a chronic inflammatory state is associated with occult AVG infection in old nonfunctioning AVGs. Twenty hemodialysis patients were identified with chronic inflammatory state based on erythropoietin dose (units/wk)/hematocrit ratio>470, serum albumin <3.3 g/dL, and CRP>25 mg/L. Among these patients, we found eight with old nonfunctioning AVGs. We then performed indium-labeled white blood cell (WBC) scans on the eight patients to screen for occult infection of old nonfunctioning AVGs. The AVGs with positive indium scan were resected and cultured. Data on hematocrit, erythropoietin dosing, serum albumin, ferritin, and CRP were obtained at 2 months following AVG resection and compared to pre-resection values. RESULTS: In study 1, the 22 patients with occult infection of old nonfunctioning AVG exhibited profound anemia and hypoalbuminemia. Their mean hemoglobin was 9.2 +/- 1.2 g/dL which improved to 11.6 +/- 0.8 g/dL (P < 0.05) 3 months after AVG resection. Their mean serum albumin was 3.3 +/- 0.5 g/dL which improved to 3.8 +/- 0.2 g/dL (P < 0.05) 3 months after AVG resection. Their mean erythropoietin dosages (units/patient/wk) fell from 14,240 +/- 350 to 6,675 +/- 455 (P < 0.05). In study 2, among the 8 patients with chronic inflammatory state and old nonfunctioning AVG, 6 (75%) had positive indium scans and underwent surgical resection that proved bacterial infection. Upon follow-up, the 2-month data showed a remarkable improvement in the following parameters: weekly erythropoietin dose/hematocrit ratio from 622 +/- 137 to 254 +/- 28 (P < 0.05), plasma ferritin values from 690 +/- 126 ng/mL to 247 +/- 42 ng/mL (P < 0.01), and plasma CRP from 56.7 +/- 9.0 to 14.5 +/- 3.8 mg/L (P < 0.01). Serum albumin values also improved from 3.07 +/- 0.08 g/dL to 3.34 +/- 0.14 g/dL (P = 0.13). Percent plasma iron saturation did not appreciably differ from baseline (20.5% +/- 4.4% to 19.8 +/- 1.9%, P = 0.89). CONCLUSIONS: Occult infection of old nonfunctioning AVG is a common cause of erythropoietin resistance and chronic inflammatory state among hemodialysis patients. Resection of old nonfunctioning AVGs with occult infection is associated with resolution of markers of chronic inflammatory state.

Algorithms↗
PubMed2002

Pheochromocytoma multisystem crisis in a patient with multiple endocrine neoplasia type IIB and pyelonephritis.

A patient with pyelonephritis developed multiorgan failure resulting in death. Clinical findings were consistent with multiple endocrine neoplasia type II, with bilateral pheochromocytomas identified by computed tomography scan. We hypothesize that either the infection or the administration of radiocontrast media led to a massive release of catecholamines from the pheochromocytomas. As a result, tissue perfusion was severely compromised, and multiorgan failure developed. This exceedingly rare complication of pheochromocytoma has been termed pheochromocytoma multisystem crisis.

Adrenal Gland Neoplasms↗