Iron sucrose: The oldest iron therapy becomes new

Several parenteral iron preparations are now available. This article focuses on iron sucrose, a hematinic, used more widely than any other for more than five decades, chiefly in Europe and now available in North America. Iron sucrose has an average molecular weight of 34 to 60 kd, and after intravenous (IV) administration, it distributes into a volume equal to that of plasma, with a terminal half-life of 5 to 6 hours. Transferrin and ferritin levels can be measured reliably 48 hours after IV administration of this agent. Iron sucrose carries no black-box warning, and a test dose is not required before it is administered. Doses of 100 mg can be administered over several minutes, and larger doses up to 300 mg can be administered within 60 minutes. The efficacy of iron sucrose has been shown in patients with chronic kidney disease (CKD) both before and after the initiation of dialysis therapy. Iron sucrose, like iron gluconate, has been associated with a markedly lower incidence of life-threatening anaphylactoid reactions and may be administered safely to those with previously documented intolerance to iron dextran or iron gluconate. Nonanaphylactoid reactions, including non-life-threatening hypotension, nausea, and exanthema, also are extremely uncommon with iron sucrose. Management of patients with the anemia of CKD mandates that we carefully examine the effectiveness and safety of this oldest of iron preparations and the accumulating present-day data regarding it and contemporaneous agents. © 2002 by the National Kidney Foundation, Inc

What Is So Bad About a Hemoglobin Level of 12 to 13 g/dL for Chronic Kidney Disease Patients Anyway?

Randomized controlled trials (RCTs) clearly indicate a possible cardiovascular morbidity and mortality risk when deliberately targeting a normal hemoglobin (Hb) concentration of 13 to 15 g/dL. By contrast, observational studies point to greater hospitalization and mortality at Hb levels \u3c11 g/dL. There are no direct data to help us determine where, within this broad range, the optimal Hb lies. In RCTs and observational studies, significant confounding from the interrelationships of anemia and epoetin resistance occurs in patients with a serious illness. Patients with comorbidities such as malnutrition and inflammatory processes are more resistant to epoetin and, invariably, require greater cumulative epoetin doses. The effect of a higher erythropoiesis-stimulating agent (ESA) dose on increasing mortality has been noted repeatedly in post hoc analyses of RCTs. It is therefore too simplistic to solely attribute the outcomes achieved in RCTs to target Hb. We discuss various mechanisms for potential harm at higher Hb levels as opposed to those that may be obtained from higher epoetin doses. For the individual patient, the therapeutic decision should center on what Hb is most appropriate at a safe ESA dose. Consequently, an Hb of 12 to 13 g/dL may be totally appropriate in some patient populations. © 2009 National Kidney Foundation, Inc

Surveillance and Monitoring of Dialysis Access

Vascular access is the lifeline of a hemodialysis patient. Currently arteriovenous fistula and graft are considered the permanent options for vascular access. Monitoring and surveillance of vascular access are an integral part of the care of hemodialysis patient. Although different techniques and methods are available for identifying access dysfunction, the scientific evidence for the optimal methodology is lacking. A small number of randomized controlled trials have been performed evaluating different surveillance techniques. We performed a study of the recent literature published in the PUBMED, to review the scientific evidence on different methodologies currently being used for surveillance and monitoring and their impact on the care of the dialysis access. The limited randomized studies especially involving fistulae and small sample size of the published studies with conflicting results highlight the need for a larger multicentered randomized study with hard clinical end points to evaluate the optimal surveillance strategy for both fistula and graft

Multiple pumps for sodium reabsorption by the perfused kidney

Multiple pumps for sodium reabsorption by the perfused kidney. Several distinct transport mechanisms responsible for sodium reabsorption by the rat kidney can be identified by studying the function of isolated perfused kidneys. Approximately one-half of the fractional sodium reabsorption by the isolated perfused rat kidney appears to depend on Na-K-adenosine triphosphatase (AT-Pase) and is inhibited by ouabain. About 15 to 20% is associated with the reabsorption of bicarbonate and is blocked by acetazolamide. This fraction of transported sodium is unaffected by ouabain and therefore does not involve Na-K-ATPase. Neither furosemide nor ethacrynic acid produce further inhibition of sodium reabsorption in a kidney already exposed to ouabain and acetazolamide. Most of the residual transport of sodium is inhibited by cooling the perfused kidney, suggesting that it is powered by metabolic rather than physical sources of energy.Multiplicité des pompes qui assurent la réabsorption du sodium par le rein perfusé. Plusieurs mécanismes de transport distincts responsables de la réabsorption de sodium par le rein de rat peuvent être identifiés par l'étude du fonctionnement de reins isolés perfusés. La moitié, approximativement, de la réabsorption fractionnelle du sodium par les reins isolés perfusés semble dépendre de la Na-K-ATPase et est inhibée par l'ouabaïne. Environ 15 à 20% sont associes à la réabsorption du bicarbonate et bloqués par l'acetazolamide. Cette fraction du sodium transporté n'est pas affectée par l'ouabaïne et donc n'implique pas la Na-K-ATPase. Ni le furosémide ni l'acide éthacrynique ne produisent d'inhibition supplémentaire de la réabsorption de sodium par un rein déjà exposé à l'ouabaïne et à l'acetazolamide. La plus grande partie du transport résiduel du sodium est inhibée par le refroidissement du rein perfusé, ce qui suggère une source d'énergie métabolique plutôt que physique

Comparison of Low-Dose Gentamicin With Minocycline as Catheter Lock Solutions in the Prevention of Catheter-Related Bacteremia

Background: Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia (CRB), but insufficient data are available about the ideal agent and dose. We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past. Methods: In this prospective, open-labeled, randomized, clinical trial of patients on long-term hemodialysis therapy, patients were randomly assigned to administration of an antibiotic lock solution of gentamicin/citrate (4 mg/mL), minocycline/EDTA, or the control solution of heparin. Patients were followed up until the study end point of CRB was reached or a censoring event occurred. Interim data analysis was performed after 6 months to assess data safety; efficacy was noted and the study was terminated early. Results: Sixty-two patients were enrolled into the study, evenly distributed in 3 arms, with data from 1 patient excluded from analysis. Seven of 20 patients in the heparin group (4.0 events/1,000 catheter days), 1 of 21 patients in the minocycline group (0.4 events/1,000 catheter days), and none of 20 patients in the gentamicin group developed bacteremia. Results were statistically significant by using 2-tailed Fisher exact test; heparin versus gentamicin, P = 0.008, and heparin versus minocycline, P = 0.020. Conclusion: Antibiotic lock solutions are superior to the standard heparin lock alone in the prevention of CRBs, and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies. © 2006 National Kidney Foundation, Inc

Iron repletion is associated with reduction in platelet counts in non-dialysis chronic kidney disease patients independent of erythropoiesis- stimulating agent use: A retrospective cohort study

Background: Iron deficiency is common in non-dialysis chronic kidney disease (ND-CKD) patients and, on occasion, requires parenteral iron therapy. We investigated the effect of intravenous iron repletion on platelet counts in ND-CKD patients with and without concomitant darbepoetin administration. Methods. We conducted a retrospective analysis of ND-CKD patients with iron deficiency anemia treated with low molecular weight iron dextran (LMWID) between 2005 and 2009 at our CKD clinic. The primary end-point was change in platelet count 60 days post infusion of LMWID in those with and without concomitant darbepoetin administration. Secondary end-points were the correlations between changes in platelet count and iron indices. Results: A total of 108 patients met inclusion and exclusion criteria. The decrease in platelet counts in response to iron repletion was statistically significant (305.72 ± 108.86 vs 255.58 ± 78.97, P = \u3c.0001). The decrease in platelet count was independent of concomitant darbepoetin use. Bivariate regression analysis between baseline platelet count and transferrin saturation by iron (TSAT) showed a negative association (βTSAT = -5.82, P =.0007) and moderate correlation (R = 0.32). Following iron treatment, the within individual changes in platelet count in 60 days were not related to changes in TSAT (βΔTSAT = -0.41, P =.399) and demonstrated a poor correlation (R = 0.10). Conclusions: Parenteral iron treatment by LMWID is associated with reduction in platelet counts in iron deficient anemic ND-CKD patients. However, ESA use in the majority of patients prior to intravenous iron administration could have altered platelet production through bone marrow competition. © 2014 Yessayan et al.; licensee BioMed Central Ltd

Intravenous iron dextran as a component of anemia management in chronic kidney disease: A report of safety and efficacy

Objective. We aimed to demonstrate safety and efficacy of intravenous (IV) low molecular weight iron dextran (LMWID) during treatment of anemic stage 3 and 4 chronic kidney disease (CKD) patients. Methods. Efficacy data was obtained by retrospective chart review of 150 consecutively enrolled patients. Patients were assigned per protocol to oral or IV iron, with IV iron given to those with lower iron stores and/or hemoglobin. Iron and darbepoetin were administered to achieve and maintain hemoglobin at 10-12 g/dL. Efficacy endpoints were mean hemoglobin and change in iron indices approximately 30 and 60 days after enrollment. Safety data was obtained by retrospective review of reported adverse drug events (ADEs) following 1699 infusions of LMWID (0.5-1.0 g). Results. Mean hemoglobin, iron saturation, and ferritin increased significantly from baseline to 60 days in patients assigned to LMWID (hemoglobin: 11.3 versus 9.4 g/dL; iron saturation: 24% versus 12.9%; ferritin: 294.7 versus 134.7 ng/mL; all P values \u3c 0.0001). Iron stores and hemoglobin were maintained in the group assigned to oral iron. Of 1699 iron dextran infusions, three ADEs occurred. Conclusions. Treatment of anemia in CKD stages 3 and 4 with LMWID and darbepoetin is efficacious. The serious ADE rate was 0.06% per infusion. © 2013 Lenar Yessayan et al

Dialysate iron therapy: Infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis

Background. Soluble iron salts are toxic for parenteral administration because free iron catalyzes free radical generation. Pyrophosphate strongly complexes iron and enhances iron transport between transferrin, ferritin, and tissues. Hemodialysis patients need iron to replenish ongoing losses. We evaluated the short-term safety and efficacy of infusing soluble ferric pyrophosphate by dialysate. Methods. Maintenance hemodialysis patients receiving erythropoietin were stabilized on regular doses of intravenous (i.v.) iron dextran after oral iron supplements were discontinued. During the treatment phase, 10 patients received ferric pyrophosphate via hemodialysis as monthly dialysate iron concentrations were progressively increased from 2, 4, 8, to 12 μg/dl and were then sustained for two additional months at 12 μg/dl (dialysate iron group); 11 control patients were continued on i.v. iron dextran (i.v. iron group). Results. Hemoglobin, serum iron parameters, and the erythropoietin dose did not change significantly from month 0 to month 6, both within and between the two groups. The weekly dose of i.v. iron (mean ± SD) needed to maintain iron balance during month 6 was 56 ± 37 mg in the i.v. iron group compared with 10 ± 23 mg in the dialysate iron group (P = 0.001). Intravenous iron was required by all 11 patients in the i.v. iron group compared with only 2 of the 10 patients receiving 12 μg/dl dialysate iron. The incidence of adverse effects was similar in both groups. Conclusions. Slow infusion of soluble iron pyrophosphate by hemodialysis may be a safe and effective alternative to the i.v. administration of colloidal iron dextran in maintenance hemodialysis patients