Anemia Management and the Delay of Chronic Renal Failure Progression

Rossert, Jérôme; Fouqueray, Bruno; Boffa, J.J.

doi:10.1097/01.asn.0000070079.54912.b6

Cited by 52 publications

(39 citation statements)

References 50 publications

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“…It is reasonable to hypothesize that the same holds true in CKD, where steadiness of hemoglobin levels is even more important because of the ischemic status typically present at the level of the kidney as of other tissues. In particular, experimental evidence has accumulated that in CKD, the major, although not exclusive, nephroprotective effect of ESA is the reduction of hypoxia, as a result of anemia correction, that diminishes tubular damage and dependent nephron loss (30). To gain full expression of these beneficial effects, BP should be adequately controlled (31)(32)(33), as in the case of our patients.…”

Section: Discussionmentioning

confidence: 89%

Stability of Target Hemoglobin Levels during the First Year of Epoetin Treatment in Patients with Chronic Kidney Disease

Nicola¹,

Conte²,

Chiodini³

et al. 2007

Clinical Journal of the American Society of Nephrology

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Background and Objectives: Instability of hemoglobin levels during epoetin therapy is a new problem in hemodialysis. We evaluated extent and correlates of time in target, that is, the time spent with hemoglobin >11 g/dl during the first year of epoetin and its association with renal survival.Design, Setting, Participants, & Measurements: Data were collected in 917 visits for 12.0 mo in 119 patients with chronic kidney disease; thereafter, patients started renal survival analysis for 10.1 mo. At baseline, hemoglobin was 10.0 ؎ 0.8 g/dl and GFR was 22.1 ؎ 14.2 ml/min per 1.73 m 2 . Results: Hemoglobin target, reached in 1.5 mo, was steadily maintained in only 24% of patients. Time in target was not merely due to differences in time to target; after first achievement of target, in fact, a reduction of hemoglobin <11 g/dl occurred in 51% of patients. At multivariate analysis, male gender, basal GFR and hemoglobin levels, first epoetin dose, and iron supplementation were directly associated with length of time in target. A lower risk for renal death (dialysis n ‫؍‬ 53; death n ‫؍‬ 8) was detected in the higher tertile of time in target (11.3 mo) versus lower tertile (3.2 mo). This difference persisted at Cox analysis after adjustment for age, gender, GFR, BP, and proteinuria.Conclusions: In chronic kidney disease, time in target during the first year of epoetin therapy is frequently short depending not only on time to target but also on post-target hemoglobin reductions, correlates with male gender, timing, and intensity of initial therapy and is coupled with better renal survival.

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Section: Discussionmentioning

confidence: 89%

Stability of Target Hemoglobin Levels during the First Year of Epoetin Treatment in Patients with Chronic Kidney Disease

Nicola¹,

Conte²,

Chiodini³

et al. 2007

Clinical Journal of the American Society of Nephrology

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“…Although administration of recombinant human EPO is a widely used approach for treating and mitigating renal anemia in chronic kidney disease patients [9], such treatment is costly and comprises the highest annual drug sales worldwide [10]. In Japan, 83% of hemodialysis patients are prescribed recombinant EPO, and the mean EPO dose was 5,231 units per week in 2006, which extrapolates to more than $6,700 per person per year [11].…”

Section: Introductionmentioning

confidence: 99%

Xenotransplanted Embryonic Kidney Provides a Niche for Endogenous Mesenchymal Stem Cell Differentiation into Erythropoietin-Producing Tissue

et al. 2012

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Recent findings have demonstrated that stem cells can differentiate into mature tissue when supplied with a niche containing factors identical to those in the normal developmental program. A niche for the development of an organ can be provided by xenotransplantation of a similar developing organ. However, this process has many technical, safety, and ethical concerns. Here, we established xenotransplantation models that control endogenous mesenchymal stem cell (MSC) differentiation into mature erythropoietin (EPO)-producing tissue in a niche provided by a developing xenometanephros. Transplantation of rat metanephroi into mouse omentum, and similarly pig metanephroi into cat omentum, led to the recruitment of host cells and EPO production. EPO-expressing cells were not differentiated from integrating vessels because they did not coexpress endothelial markers (Tie-2 and VE-cadherin). Instead, EPOexpressing cells were shown to be derived from circulating host cells, as shown by enhanced green fluorescent protein (EGFP) expression in the grown transplants of chimeric mice bearing bone marrow from a transgenic mouse expressing EGFP under the control of the EPO promoter. These results suggest that donor cell recruitment and differentiation in a xenotransplanted developing organ may be consistent between species. The cells responsible for EPO expression were identified as MSCs by injecting human bone marrow-derived MSCs and endothelial progenitor cells into NOD/SCID mice. Furthermore, using metanephroi from transgenic ER-E2F1 suicide-inducible mice, the xenotissue component could be eliminated, leaving autologous EPO-producing tissue. Our findings may alleviate adverse effects due to long-lasting immunosuppression and help mitigate ethical concerns.

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“…The deterioration is often attributed to systemic hypertension, proteinuria, hyperlipidaemia [3,4], and intra glomerular hypertension [5]. Smoking, obesity and anaemia are considered other risk factors for progression of chronic kidney disease [6][7][8].…”

Section: Definition Of Chronic Kidney Diseasementioning

confidence: 99%