Low-molecular weight iron dextran and iron sucrose have similar comparative safety profiles in chronic kidney disease

Serious adverse events that occur with the administration of iron dextran are due to the high molecular weight preparations. Conclusions that iron sucrose and ferric gluconate are safer than iron dextran may be premature. Published literature comparing safety profiles of available parenteral iron products is reviewed. Administration of iron salts to pre-dialysis patients with chronic kidney disease may not be optimal. We recommend the total dose infusion of low molecular weight iron dextran as an option for iron replacement.     

Proinflammatory effects of iron sucrose in chronic kidney disease

Inflammation is a central component of progressive chronic kidney disease (CKD). Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD. Parenteral iron provokes oxidative stress in patients with CKD; however, its potential to provoke an inflammatory response is unknown. In 20 veterans with CKD, 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 (MCP-1) were measured at timed intervals over 24 h. Patients were then randomized to placebo or N-acetyl cysteine (NAC) 600 mg b.i.d. and the experiment was repeated at 1 week. Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits (P < 0.0001 for time effect). Urinary excretion peaked at 30 min and plasma concentration at 15 min. Plasma MCP-1 concentration fell from 164 +/- 17.7 to 135 +/- 17.7 pg/ml with NAC, whereas it remained unchanged from 133 +/- 12.5 to 132 +/- 17.7 pg/ml with placebo (P=0.001 for visit x antioxidant drug interaction). There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2. At the baseline visit, the urinary excretion rate averaged 305 +/- 66 pg/min and at the second visit 245 +/- 67 pg/min (mean difference 60 +/- 28 pg/min, P = 0.030). There was no improvement in urinary MCP-1 excretion with NAC. In conclusion, iron sucrose causes rapid and transient generation and/or release of MCP-1 plasma concentration and increases urinary excretion rate, and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC. These results may have implications for the progression of CKD with parenteral iron.     

The safety and efficacy of ferumoxytol therapy in anemic chronic kidney disease patients

BACKGROUND: Administration of safe and effective iron therapy in patients with chronic kidney disease is a time consuming process. This phase II clinical trial studied ferumoxytol, a semi-synthetic carbohydrate-coated iron oxide administered by rapid intravenous injection to anemic chronic kidney disease patients (predialysis or undergoing peritoneal dialysis). METHODS: Inclusion criteria included hemoglobin < or =12.5 g/dL and transferrin saturation < or =35%. Twenty-one adult patients were randomized to receive ferumoxytol in a regimen of 4 doses of 255 mg iron in 2 weeks or 2 doses of 510 mg iron in 1 to 2 weeks. Ferumoxytol was administered at a rate of up to 30 mg iron/sec. RESULTS: The maximum hemoglobin response following ferumoxytol administration occurred at 6 weeks, increasing from a baseline of 10.4 +/- 1.3 g/dL to 11.4 +/- 1.2 g/dL (P < 0.05). Ferritin increased from a baseline of 232 +/- 216 ng/mL to a maximum of 931 +/- 361 ng/mL at 2 weeks (P < 0.05), while the baseline transferrin saturation increased from 21 +/- 10% to 37 +/- 22% at 1 week (P < 0.05). Seven adverse events in 5 patients during this trial were deemed possibly related to ferumoxytol, none serious. These events included constipation, chills, tingling, a gastrointestinal viral syndrome, delayed pruritic erythematous rash, and transient pain at the injection site. CONCLUSION: Although larger studies are required, this small study demonstrates that ferumoxytol can be safe and effective in increasing iron stores, is associated with an increased hemoglobin response, and is well tolerated at a rapid infusion rate.     

Comparing the efficacy of intravenous iron and oral iron in nondialysis patients with chronic kidney disease

This Practice Point commentary discusses the findings and limitations of a phase III trial by Spinowitz et al. that compared oral and intravenous iron therapies in nondialysis patients with chronic kidney disease. In total, 304 patients were randomly assigned in a 3:1 ratio to receive either two 510 mg doses of intravenous ferumoxytol within 5+/-3 days or 200mg of elemental oral iron daily for 21 days. At day 35, hemoglobin levels had increased significantly more in patients who had received intravenous ferumoxytol than in those who had received oral iron therapy. Ferumoxytol was well tolerated. The superiority of ferumoxytol over other intravenous iron preparations, however, needs to be investigated, and optimal serum ferritin levels for the nondialysis CKD population need to be defined.     

The comparative safety of various intravenous iron preparations in chronic kidney disease patients

The relative safety of parenteral iron preparations is a controversial issue in the management of anemia in chronic kidney disease (CKD), as direct head-to-head comparative trials are lacking. In this study, patients of CKD were randomized to receive intravenous low molecular weight iron dextran (ID), sodium ferrigluconate complex (SFGC), and iron sucrose (IS) at doses and infusion rates recommended by the product manufacturer. One time test dose was used only for ID and SFGC. A total of 2,980 injections (n = 339) of i.v. iron was given, and 49 patients (14.45% per patient) and a total of 56 adverse events (1.88% per infusion) were noted. Odds ratios (OR) of serious adverse drug events (ADE; i.e., death, anaphylaxis, or suspected immuno-allergic events) per patient was not significant between ID vs. SFGC (3.566) and SFGC vs. IS (2.129), whereas that between ID vs. IS (7.594) was highly significant (p = 0.034). OR of serious ADE exposure was significantly higher in ID vs. SFGC (OR = 5.670, p = 0.0147) and ID vs. IS (OR = 7.799, p < 0.001). No significant difference was seen between the three groups in terms of non-serious ADEs. Drug discontinuation occurred significantly more often with ID. One patient who developed anaphylactoid reaction with SFGC and ID tolerated iron sucrose well.     

Rapid, high-dose intravenous iron sucrose therapy in 2 Jehovah's Witness patients with severe anemia, iron deficiency and chronic kidney disease

AIMS: Two patients with chronic kidney disease presented with severe anemia and iron deficiency. Because of their religious beliefs, red blood cell transfusions were not possible, and an aggressive therapeutic regimen of iron replenishment was instituted. MATERIAL AND METHODS: The regimen included epoetin, folic acid and high-dose intravenous iron sucrose infusions over multiple successive days (total dosages of 2 and 3.5 g). RESULTS: The patients' iron stores were replenished and an erythropoietic response ensued subsequent to this aggressive and unique therapeutic regimen. There were no side effects observed which could be attributed to iron sucrose, and both patients stabilized and were discharged after 3 - 4 weeks. CONCLUSION: In patients with chronic kidney disease who are severely anemic and iron-deficient and where transfusions are not possible, an aggressive regimen of multiple high-dose iron sucrose infusions may be both safe and effective.     

The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease

International Urology and Nephrology - Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies...     

慢性肾小球肾炎患者血清新蝶呤的水平及其意义

静脉使用蔗糖铁已被广泛地用于血液透析患者肾性贫血的治疗,但在非透析慢性肾脏病(NDCKD)患者中使用不多,大剂量蔗糖铁在NDCKD患者中使用的研究报道更少.我科对使用大剂量蔗糖铁治疗肾性贫血伴铁缺乏的NDCKD患者的安全性及有效性进行了观察.     

静脉补铁与口服补铁治疗非透析慢性肾功能不全患者贫血效果比较的Meta分析

目的通过系统评价评估静脉补铁与口服补铁两种补铁方法对治疗非透析慢性肾功能不全(ND-CKD)患者贫血的疗效。 方法通过计算机并结合手工检索,检索EMBASE、PUBMED、Cochrane Library,检索时间截止到2017年12月1日,查找所有关于静脉补铁与口服补铁治疗ND-CKD患者贫血疗效的全部外文随机对照试验(RCT)。所得数据采用Rev Man 5.0软件进行Meta分析。 结果共纳入11项外文RCT研究,合计共1 707例患者,其中静脉补铁852例,口服补铁855例。分析结果示,与口服补铁相比,静脉补铁可显著提高血红蛋白(WMD 0.39 g/dl,95%CI,0.26～0.52;P<0.0001)、转铁蛋白饱和度(TSAT)(WMD 3.97%; 95%CI,2.24～5.7;P<0.0001)及铁蛋白水平(WMD,244.51 ng/ml,95%CI,185.51～303.52; P<0.0001);两种补铁方法的不良事件发生率无明显差别(RR,0.79; 95%CI,0.44～1.44;P＝0.45)。 结论通过系统评价得出：与口服补铁相比,静脉补铁对治疗非透析慢性肾功能不全患者的贫血疗效较好。     

Efficacy and safety of lanthanum carbonate in chronic kidney disease patients with hyperphosphataemia

Hyperphosphataemia is a frequent complication in patients with chronic kidney disease and is associated with increased cardiovascular morbidity. Lanthanum carbonate is a calcium-free phosphate binder indicated in patients with chronic kidney disease. Its digestive absorption is minimal (<0,002%). This minimal quantity is rapidly excreted by the hepatobiliary system, but there is an initial accumulation in liver and bone, which reaches a plateau within a few weeks. Long-term follow-up until six years did not show any bone or liver toxicity. Efficacy and safety of lanthanum carbonate have been assessed in randomized trials. The most common side effects reported were gastrointestinal and occurred with a similar incidence than with placebo and other phosphate binders. Hypercalcemia was less frequent than with calcium carbonate. This review highlights pharmacokinetic, pharmacodynamic and clinical (efficacy and safety) properties of lanthanum carbonate and discusses its place in the management of hyperphosphataemia in patients with chronic kidney disease.     

Zinc levels after iron supplementation in patients with chronic kidney disease.

OBJECTIVE: The goal of this study was to evaluate the effects of iron supplementation on zinc distribution in nondialyzed chronic kidney disease (CKD) patients. DESIGN: Prospective nonrandomized observational study. SETTING: Outpatients of the Nephrology Division at Federal University of S?o Paulo. PATIENTS: Zinc and iron status of 38 nondialyzed patients (63% male; creatinine clearance, 34.5+/-13.3 mL/min/1.73 m2) was evaluated before and after 3 intramuscular injections of 100 mg iron each. MAIN OUTCOME MEASURES: The following parameters were analyzed: erythrocytes and plasma zinc, zinc protoporphyrin (ZPP), plasma ferritin, transferrin saturation (TFS), and total iron. The patients' diets were analyzed by the Association of Official Analytical Chemists method for macronutrients, and neutron activation analysis was used for iron and zinc concentration determinations. RESULTS: Ferritin and TFS increased from 86.3+/-67.5 ng/mL to 105.4+/-63.7 ng/mL and from 19.5+/-7.4% to 23.2+/-6.7% (P <.05), respectively, after iron supplementation. Absolute iron deficiency (ferritin <100 microg/L and TFS <20%) was present in 41% of the patients and decreased to 15.7% after iron treatment. In comparison with baseline values (76.4+/-16.7 microg/dL), there were no significant changes in plasma zinc levels, but after supplementation the number of patients with low plasma zinc levels decreased from 46.1% to 23.7% (P =.08). At baseline, erythrocyte zinc was 49.0+/-7.6 microg Zn/gHb, and 76.3% of the patients had high erythrocyte zinc concentration. After iron treatment, erythrocyte zinc decreased to 45.5+/-7.3 microg Zn/gHb (P =.001). No significant change was observed in ZPP concentration. The analysis of the diet showed energy and protein intakes of 26.2+/-7.1 kcal/kg/day and 0.89+/-0.2 g/kg/day, respectively, and a low intake of both iron and zinc. CONCLUSIONS: This study suggests that iron deficiency may contribute to the inadequate distribution of zinc in patients with CKD and that iron supplementation may decrease the abnormal elevated erythrocyte zinc levels of these patients.     

Emotional management and biological markers of dietetic regimen in chronic kidney disease patients

The aim of the study was to investigate the association between psychological characteristics and biological markers of adherence in chronic kidney disease patients receiving conservative therapy, hemodialysis, peritoneal dialysis (PD), or kidney transplantation.

Seventy-nine adult patients were asked to complete the following questionnaires: Toronto Alexithymia scale, Snaith–Hamilton Pleasure Scale, and Short Form Health Survey. Biological markers of adherence to treatment were measured.

Peritoneal dialysis patients showed a lower capacity to feel pleasure from sensorial experience (p?=?.011) and a higher values of phosphorus compared to the other patients’ groups (p?=?.0001).

The inability to communicate emotions was negatively correlated with hemoglobin levels (r?=??(0).69; p?=?.001) and positively correlated with phosphorus values in the PD patients (r?=?.45; p?=?.050).

Findings showed higher psychological impairments and a lower adherence to the treatment in PD patients and suggest the implication of emotional competence in adherence to treatment.     

Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease

BACKGROUND: Intravenous iron is widely prescribed in patients with chronic kidney disease (CKD) and can cause oxidative stress. The relationship of oxidative stress and renal injury in patients with CKD is unknown. Whether renal injury can occur at a time point when transferrin is incompletely saturated is also unclear. METHODS: We conducted a randomized, open-label, parallel group trial to compare the oxidative stress induced by intravenous administration of 100 mg iron sucrose over 5 minutes and its protection with N-acetylcysteine (NAC) in 20 subjects with stage 3 or 4 CKD. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, oxidative stress by malondialdehyde (MDA) measurement by high-performance liquid chromatography, and renal injury by enzymuria and proteinuria. Reduced and oxidized glutathione and free radical scavengers as well as urinary monocyte chemoattractant protein-1 were also measured. RESULTS: Parenteral iron increased plasma concentration and urinary excretion rate of MDA, a biomarker of lipid peroxidation, within 15 to 30 minutes of iron sucrose administration. This was accompanied by enzymuria and increase in proteinuria. In contrast, saturation of transferrin was not maximally seen until 3 hours after the end of infusion. Oxidative stress, enzymuria and proteinuria were transient and were completely resolved in 24 hours. NAC reduced acute generation of systemic oxidative stress but failed to abrogate proteinuria or enzymuria. CONCLUSION: Intravenous iron produces oxidative stress that is associated with transient proteinuria and tubular damage. The rapid production of oxidative stress even when transferrin is not completely saturation suggests free iron independent mechanism(s) to be operative in producing oxidative stress and transient renal injury. Long-term implications of these findings need further study.     

Oxidants and iron in chronic kidney disease

Oxidants derived either from leukocytes in proliferative glomerular nephritis or from resident glomerular cells in nonproliferative glomerulonephritis have been shown to have several biologic effects relevant to chronic kidney disease. These include: the ability of oxidants to damage glomerular basement membrane (GBM) and to directly induce proteinuria; effects that would lead to a fall in the glomerular filtration rate; and effects that would account for the morphologic changes observed in chronic kidney disease. In experimental models the role of oxidants has been demonstrated in both proliferative glomerulonephritis (e.g., anti-GBM antibody disease) as well as experimental models of minimal change disease and membranous nephropathy. Oxidants have also been shown to be an important mediator of the various pathways that have been implicated in diabetic nephropathy. Antioxidants and iron chelators have also been shown to retard functional and morphologic changes observed in progressive kidney disease. Taken together, these experimental studies suggest an important role of oxidants in chronic kidney disease.     

利塞膦酸钠治疗老年慢性肾脏病伴骨质疏松的疗效与安全性评价

目的评价利塞膦酸钠治疗老年慢性肾脏病(CKD)伴骨质疏松症的临床疗效及安全性。方法回顾性分析65例老年CKD2期或3期合并骨质疏松症患者的临床资料,分为应用利塞膦酸钠联合碳酸钙D3咀嚼片的治疗组32例及单独口服碳酸钙D3咀嚼片的对照组33例,疗程均为6个月。通过检测治疗前、后两组患者的骨密度、骨代谢指标如总1型胶原氨基端延长肽(t-P1NP)、N-端中段骨钙素(N-MID OC)、β-胶原降解产物(β-CTx)、25-羟基维生素D(25-OH-VD)等,对利塞膦酸钠的有效性进行评估,并评价其安全性。结果治疗6个月后两组患者T值及腰2~4、股骨颈的骨密度均显著升高(分别为P0.01和P0.05),且治疗组治疗后腰2~4、股骨颈的骨密度明显高于对照组治疗后(P0.05)。治疗组骨密度改善的总有效率(84.38%)显著高于对照组(60.61%)(P0.05)。治疗组治疗后t-P1NP、N-MID OC、β-CTx水平显著下降,25-OH-VD明显升高,与治疗前和对照组比较差异有统计学意义(P0.05)。治疗组治疗6个月后VAS评分显著下降(P0.01),且显著低于对照组(P0.05)。治疗组新骨折发生率显著低于对照组(P0.05)。治疗中未出现与药物相关的严重不良反应。结论利塞膦酸钠对于估算肾小球滤过率(e GFR)≥30 m L/(min·1.73m2)的老年CKD伴骨质疏松症的治疗有效,优于单用钙剂,且安全性较好。     

A systemic review and meta-analysis on the efficacy and safety of ferumoxytol for anemia in chronic kidney disease patients

PurposeTo evaluate the efficacy of ferumoxytol, relative to conventional iron supplement formulations, on hemoglobin levels, ferritin level, and adverse event incidence in chronic kidney disease patients.MethodsWe performed a systematic search of six academic databases (EMBASE, CENTRAL, Scopus, PubMed, Web of sciences, and MEDLINE), adhering to PRISMA guidelines. We performed a meta-analysis on relevant studies to evaluate the overall influence of ferumoxytol, relative to conventional iron supplement formulations, on hemoglobin levels, ferritin level, and treatment related treatment emergent adverse events (TEAEs) incidence in chronic kidney disease patients.ResultsSeven eligible studies were identified from a total of 1397 studies. These studies contained data on 3315 participants with chronic kidney disease (mean age: 59.2 ± 4.6 years). A meta-analysis revealed that ferumoxytol administration had positive effects on hemoglobin levels (Hedge’s g statistic: 0.51) and ferritin level (0.88), transferrin saturation (0.39). Besides, we also report reduced incidence of treatment related TEAEs (−0.24) for patients consuming ferumoxytol as compared conventional iron supplement formulations.ConclusionsThis meta-analysis provides preliminary evidence that ferumoxytol use exerts beneficial effects on the overall hematological outcomes in patients with chronic kidney disease. This study also reports improved treatment related safety profile for ferumoxytol when compared with conventional iron formulations. The findings from this study can have direct implications in forming best practice guidelines for managing anemia in patients with chronic kidney disease.     

Growth hormone treatment of infants with chronic kidney disease: requirement,efficacy, and safety

Growth failure is still a challenge in infants suffering from chronic kidney disease (CKD). Persistent growth failure is associated with the excessive mortality rate seen in these patients and markedly hampers later psychosocial integration. Infancy is an extremely sensitive period of growth, since physiological growth rates are several times higher than in later life. Growth failure in infants with CKD has multiple reasons, originating preferentially from malnutrition and, to a lesser extent, from water and electrolyte losses, metabolic acidosis, anemia, and renal osteodystrophy. Although, recombinant human growth hormone (rhGH) has been proven to be safe and effective for treatment of uremic growth failure in later childhood, its usage has not been adequately investigated in infants. Mencarelli et al. (Pediatric Nephrology 24:1039–1046, 2009) reported on their retrospective analysis of the longitudinal growth of 27 infants with early onset CKD that were receiving either standard therapy or additional rhGH treatment. Although their results were encouraging with respect to a sustained catch-up growth in rhGH-treated children, this issue has to be further addressed in prospective randomized controlled trials. In these trials special emphasis has to be given to the safety of this treatment modality, since rhGH might induce insulin resistance and glucose intolerance, especially in infants on high caloric intake and peritoneal dialysis. Remark from the EditorsThe article by Mencarelli et al. was published in the May 2009 issue of the Journal and can be found at doi:.     

The odontogenic-related microinflammation in patients with chronic kidney disease

Objectives: This study estimated plasma levels of interleukin IL-1β, IL-6, tumour necrosis factor-α (TNF-α), interferon-γ (INF-γ) in chronic kidney disease (CKD) patients with a single odontogenic pathology. Material and methods: Forty-nine selected adult CKD patients with single odontogenic pathology based on clinical and X-ray examination: patients after proper root canal treatment, without periapical lesions (n?=?12), with pulp necrosis (n?=?7), with asymptomatic periapical lesions (n?=?22), with periodontal disease (n?=?8), and 14 with healthy teeth were enrolled. Patients with coexisting different dental pathologies and the evidence of other infection were excluded. In all patients plasma concentrations of CRP, IL-1β, IL-6, TNF-α, and INF-γ were measured. Results: Patients with periodontitis were characterized by increased concentrations of IL-6 and TNF-α. Those with pulp necrosis had significantly more frequently serum CRP level over 2?mg/L and presented significantly elevated IL-6, but decreased TNF-α concentration than in the subjects with healthy teeth. In patients with periapical lesions and patients after root canal therapy, the concentrations of cytokines did not indicate for the systemic inflammation. Conclusions: Periodontitis and pulp necrosis are important sources of systemic microinflammation in CKD patients. Plasma concentrations of IL-6 and TNF-α appear to be more sensitive markers of odontogenic inflammation in CKD patients than CRP.