2008 November 14

Erythropoiesis-stimulating agents in oncology.

J Natl Compr Canc Netw Start a Discussion »

Nov 142008

Erythropoiesis-stimulating agents in oncology.

J Natl Compr Canc Netw. 2008 Jul;6(6):565-75

Authors: Glaspy JA

Patients who have cancer, particularly those undergoing chemotherapy, frequently become anemic. Therapy with erythropoiesis-stimulating agents (ESAs) is associated with an increase in hemoglobin levels, a reduction in transfusion requirements, and, according to many clinical trialists and experienced clinicians, an improvement in functional status, productivity, and quality of life. Several randomized trials of ESAs in patients who have cancer have recently reported inferior outcomes in tumor progression or survival, raising appropriate concerns about the safety of ESAs in oncology. However, 3 important caveats to these reports exist. First, these clinical trials did not reflect the common use of ESAs in oncology practice (i.e., to treat, rather than prevent, anemia in patients undergoing chemotherapy). Second, the trials were seriously flawed and did not meet reasonable standards for cancer progression or survival trials. Third, during the same period, randomized trials were presented or published that showed no negative impact on tumor progression or survival; these trials have approximately the same shortcomings as trials that suggest a safety issue exists. The lack of definitive answers about the safety of ESAs for treating chemotherapy-related anemia has placed physicians, regulators, and most importantly patients in a difficult position that can only be addressed with additional data. This article reviews relevant preclinical and clinical available data to help improve understanding and guide decision making.

PMID: 18597710 [PubMed - indexed for MEDLINE]

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Intravenous iron in oncology.

J Natl Compr Canc Netw Start a Discussion »

Nov 142008

Intravenous iron in oncology.

J Natl Compr Canc Netw. 2008 Jul;6(6):585-92; quiz 592

Authors: Auerbach M, Ballard H

Intravenous iron (IV Fe) as an adjunct to therapy with erythropoiesis- stimulatory agents (ESAs) is standard care in dialysis-associated anemia, adding huge increments in hemoglobin and hematopoietic responses and decreased transfusions without significant toxicity. Cost savings, decreased exposure to ESAs, and decreased times to reach target hemoglobins are realized. Although similar benefits have been seen in all studies performed in patients with chemotherapy-induced anemia (CIA), experts are reluctant to incorporate routine use of IV Fe into treatment, largely because of misinterpretation and misunderstanding of the clinical nature of adverse events reportedly associated with its administration. IV Fe is therefore underused in oncology patients with anemia. Published experience with more than 1000 patients in clinical trials involving the use of IV Fe suggests minimal toxicity and substantial benefit are experienced when high molecular weight iron dextran is avoided. This article presents evidence recommending routine incorporation of IV Fe into treatment for CIA.

PMID: 18597712 [PubMed - indexed for MEDLINE]

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Radiocontrast-induced acute kidney injury.

Nephron Physiol Start a Discussion »

Nov 142008

Radiocontrast-induced acute kidney injury.

Nephron Physiol. 2008;109(4):p61-72

Authors: McCullough PA

Many radiographic studies and procedures use iodinated contrast media and consequently pose the risk of contrast-induced acute kidney injury (AKI). This is an important complication, which accounts for a significant number of cases of hospital-acquired renal failure associated increased hospital length of stay and increased mortality. Sustained reductions in renal blood flow, hypoxic injury, direct cellular toxicity by the contrast media, and superimposed organ injury are all believed to play a role in this form of AKI. Avoidance of dehydration and multimodality prevention measures may reduce rates of this problem in patients at risk. Contrast-induced AKI is likely to remain a significant challenge for specialists in the future since the patient population is aging, chronic kidney disease and diabetes are coming more common, and use of iodinated contrast is growing.

PMID: 18802377 [PubMed - indexed for MEDLINE]

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Acute kidney injury: new concepts. Hepatorenal syndrome: the role of vasopressors.

Nephron Physiol Start a Discussion »

Nov 142008

Acute kidney injury: new concepts. Hepatorenal syndrome: the role of vasopressors.

Nephron Physiol. 2008;109(4):p73-9

Authors: Moreau R, Lebrec D

Type 1 hepatorenal syndrome (HRS) is prerenal failure specific to decompensated cirrhosis. In patients with HRS, there is marked splanchnic/systemic vasodilation resulting in arterial hypotension, arterial baroreceptor unloading, overstimulation of the sympathetic nervous and renin-angiotensin systems. This reflex neurohumoral hyperactivity via endogenous vasoconstrictors/vasopressors such as angiotensin II and noradrenaline induces arterial vasoconstriction in different extrasplanchnic vascular beds (including preglomerular arteries in the kidneys). Decreased arterial pressure (i.e. low renal perfusion pressure) and preglomerular vasoconstriction are thought to play a major role in the decline of the glomerular filtration rate (GFR). Nonrandomized studies in patients with HRS have shown that the administration of a splanchnic vasoconstrictor (vasopressin analogue or alpha(1)-adrenoceptor agonist), usually combined with intravenous albumin, causes increases in arterial pressure, arterial baroreceptor uploading, decreased neurohumoral activity, decreased renal vascular resistance, and increased GFR. Randomized clinical trials have shown that treatment with a combination of the vasopressin analogue terlipressin and intravenous albumin improves renal function in patients with type 1 HRS. Vasopressor therapy with terlipressin plus intravenous albumin is the medical treatment of choice for type 1 HRS.

PMID: 18802378 [PubMed - indexed for MEDLINE]

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Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis.

Am J Kidney Dis Start a Discussion »

Nov 142008

Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis.

Am J Kidney Dis. 2008 Nov;52(5):897-906

Authors: Rozen-Zvi B, Gafter-Gvili A, Paul M, Leibovici L, Shpilberg O, Gafter U

BACKGROUND: Iron supplementation is essential for the treatment of patients with anemia of chronic kidney disease (CKD). It is not clear which is the best method of iron administration. STUDY DESIGN: Systematic review and meta-analysis. A search was performed until January 2008 of MEDLINE, Cochrane Central Register of Controlled Trials, conference proceedings in nephrology, and reference lists of included trials. SETTING & POPULATION: Patients with CKD (stages III to V). We included dialysis patients and patients with CKD not on dialysis therapy (hereafter referred to as patients with CKD). SELECTION CRITERIA FOR STUDIES: We included all randomized controlled trials regardless of publication status or language. INTERVENTION: Intravenous (IV) versus oral iron supplementation. OUTCOMES MEASURES: Primary outcomes assessed: absolute hemoglobin (Hb) level or change in Hb level from baseline. We also assessed all-cause mortality, erythropoiesis-stimulating agent requirement, adverse events, ferritin level, and need for renal replacement therapy in patients with CKD. RESULTS: 13 trials were identified, 6 including patients with CKD and 7 including dialysis patients. Compared with oral iron, there was a significantly greater Hb level in dialysis patients treated with IV iron (weighted mean difference, 0.83 g/dL; 95% confidence interval, 0.09 to 1.57). Meta-regression showed a positive association between Hb level increase and IV iron dose administered and a negative association with baseline Hb level. For patients with CKD, there was a small but significant difference in Hb level favoring the IV iron group (weighted mean difference, 0. 31 g/dL; 95% confidence interval, 0.09 to 0. 53). Data for all-cause mortality were sparse, and there was no difference in adverse events between the IV- and oral-treated patients. LIMITATIONS: There was significant heterogeneity between trials. Follow-up was limited to 2 to 3 months. CONCLUSIONS: Our review shows that patients on hemodialysis therapy have better Hb level response when treated with IV iron. For patients with CKD, this effect is small.

PMID: 18845368 [PubMed - indexed for MEDLINE]

Link to Article at PubMed