Parenteral iron treatment induces MCP-1 accumulation in plasma, normal kidneys, and in experimental nephropathy

Zager, Richard A.

doi:10.1111/j.1523-1755.2005.00565.x

Cited by 47 publications

(36 citation statements)

References 48 publications

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“…In this regard and relevant to this Frontiers in Nephrology series, concerns have been raised recently regarding the potential toxicity of parenteral preparations of iron (62,63), the latter of established efficacy and benefit in the therapy of iron-deficiency anemia. Interestingly, these preparations also induce HO-1 (64).…”

Section: Resultsmentioning

confidence: 99%

Physiology and Pathophysiology of Heme

Tracz

Alam

Nath

2007

Journal of the American Society of Nephrology

291

260

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An iron-containing, tetrapyrrole ring, heme is an essential prosthetic group in an array of proteins that comprehensively affect cellular function and metabolism; yet "free" heme in sufficient amounts can be damaging to the kidney and other organs because of its bioreactivity and pro-oxidant effects. This review discusses the cellular metabolism of heme in health and disease and covers such areas as the synthesis of heme and its utilization in heme proteins; mechanisms underlying the toxicity of heme; and the extent to which pathophysiologic processes, such as renal incorporation of heme proteins or destabilization of intracellular heme proteins, increase intracellular levels of heme and provoke renal injury. The main catabolic process that degrades heme, the heme oxygenase (HO) system, is reviewed, and evidence for the protective effects of HO-1 against acute and chronic heme/heme protein-induced renal injury is summarized. Finally, current views regarding the molecular basis for heme-induced upregulation of HO-1 are discussed.

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Section: Resultsmentioning

confidence: 99%

Physiology and Pathophysiology of Heme

Tracz

Alam

Nath

2007

Journal of the American Society of Nephrology

291

260

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“…This, indeed, seemed to be the case. After intravenous FeS injection, marked increases in plasma and renal cortical MCP-1 levels resulted (21). This was accompanied by elevations in renal cortical (as well as extrarenal tissue) MCP-1 mRNA.…”

Section: Fe As a Participant In Renal Disease Progressionmentioning

confidence: 94%

Parenteral Iron Compounds

Zager

2006

Clinical Journal of the American Society of Nephrology

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Ferric iron (Fe)-carbohydrate complexes are widely used for treating Fe deficiency in patients who are unable to meet their Fe requirements with oral supplements. Intravenous Fe generally is well tolerated and effective in correcting Fe-deficient states. However, the complexing of Fe to carbohydrate polymers does not block its potent pro-oxidant effects; systemic free radical generation and, possibly, tissue damage may result. The purpose of this review is to (1) underscore the capacity of currently used parenteral Fe formulations to induce oxidative stress, (2) compare the severity of these oxidant reactions with those that result from unshielded Fe salts and with each other, and (3) speculate as to the potential of these agents to induce acute renal cell injury and augment systemic inflammatory responses. The experimental data that are reviewed should not be extrapolated to the clinical setting or be used for clinical decision making. Rather, it is hoped that the information provided herein may have utility for clinical hypothesis generation and, hence, future clinical studies. By so doing, a better understanding of Fe's potential protean effects on patients with renal disease may result.

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“…We did not study the mechanism of proteinuria, but it may relate to acute hemodynamic effects on the glomerular circulation or transient dysfunction of the cubulin-megalin pathway. Although the effects of IV iron on renal hemodynamics have not been studied, iron sucrose is known to increase blood and urine cytokine concentrations in animals (20) and among patients with CKD (21), and this may mediate the proteinuria.…”

Section: Discussionmentioning

confidence: 99%

Proteinuria Induced by Parenteral Iron in Chronic Kidney Disease—A Comparative Randomized Controlled Trial

Agarwal

Leehey

Olsen³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground 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.

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Parenteral iron treatment induces MCP-1 accumulation in plasma, normal kidneys, and in experimental nephropathy

Cited by 47 publications

References 48 publications

Physiology and Pathophysiology of Heme

Physiology and Pathophysiology of Heme

Parenteral Iron Compounds

Proteinuria Induced by Parenteral Iron in Chronic Kidney Disease—A Comparative Randomized Controlled Trial

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