Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients

Jungers, Paul; Choukroun, Gabriel; Oualim, Zouhir; Robino, Christophe; Nguyen, Anh‐Thu; Man, N. K.

doi:10.1093/ndt/16.2.307

Cited by 173 publications

(90 citation statements)

References 16 publications

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“…Several retrospective trials have suggested that correction of anaemia with erythropoietin may delay the onset of dialysis in predialysis patients [32,33]; however, the benefits of treating anaemia associated with early diabetic nephropathy are still uncertain. This observational study did not attempt to determine whether correction of anaemia in early stages of diabetic kidney disease attenuates the decline rate of kidney function.…”

Section: Discussionmentioning

confidence: 99%

Lower haemoglobin level and subsequent decline in kidney function in type 2 diabetic adults without clinical albuminuria

et al. 2006

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Aims/hypothesis: Anaemia has been suggested to be an independent risk factor for subsequent progression of advanced diabetic nephropathy; however, the relationship between haemoglobin levels and progression of nephropathy in patients without clinical albuminuria is unknown. Methods: We conducted this prospective hospital-based cohort study of 464 type 2 diabetic patients (149 women and 315 men, 55±13 [mean±SD] years of age) with serum creatinine <177 μmol/l (2.00 mg/dl) and urinary albumin : creatinine ratio <300 mg/g creatinine. GFR was estimated using the equation formulated by the Modification of Diet in Renal Disease Study group, refitted for Japanese individuals. Most patients had haemoglobin concentrations in the normal range (144±15 g/l), only modest renal impairment (GFR: 74.8±14.5 ml min −1 1.73 m −2 ), and normal urinary albumin levels (81.5/18.5% with normo-/microalbuminuria). The primary outcome measurement was the rate of change in GFR determined by regression analysis with GFR as a function of time. Patients were followed up for a mean observation period of 5.0±0.9 (range: 2.5 to 6.2) years. Results: Univariate and multiple regression analyses yielded a significant association between the rate of change in GFR and baseline haemoglobin concentration. After adjusting for covariates, the rate of decline in GFR was significantly greater in patients in the lowest haemoglobin quartile (−3.27 ml min −1 1.73 m −2 year −1 ) than in the third (−2.71 ml min −1 1.73 m −2 year −1 , p=0.024) and highest quartiles (−2.78 ml min −1 1.73 m −2 year −1 , p=0.046). Conclusions/interpretation: Lower haemoglobin concentrations in type 2 diabetic patients without clinical albuminuria may be a significant predictor of subsequent decline in GFR.

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Section: Discussionmentioning

confidence: 99%

Lower haemoglobin level and subsequent decline in kidney function in type 2 diabetic adults without clinical albuminuria

et al. 2006

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“…The most commonly reported SAEs during the first 22 wk of treatment were congestive heart failure (2%) and chronic renal failure (2%). The incidence of SAEs over the (8) 8 (6) 6 (5) 24 (6) Subjects with serious adverse events 19 (15) 27 (22) 28 (22) 74 (20) Subjects with confirmed thromboembolic vascular events 2 (2) 2 (2) 3 (2) 7 (2) Subjects with hypertension 14 (11) 11 (9) 6 (5) 31 (8) Subjects with adverse events leading to study discontinuation 1 (1) 1 (1) 2 (2) 4 (1) Subjects who died 0 (0) 6 (5) 3 (2) 9 (2) During the entire 44-wk treatment period Subjects with adverse events 98 (80) 98 (78) 107 (86) 303 (81) Subjects with drug-related adverse events a 11 (9) 11 (9) 15 (12) 37 ( (4) 8 (6) 15 (4) Subjects with hypertension 16 (13) 18 (14) 12 (10) 46 (12) Subjects with adverse events leading to study discontinuation 3 (2) 3 (2) 5 (4) 11 (3) Subjects who died 4 (3) 6 (5) 4 (3) 14 (4) Treatment-emergent adverse events defined as all adverse events that occurred after the first dose of study drug. Incidence is based on the number of subjects experiencing at least one adverse event and not the number of events.…”

Section: Safetymentioning

confidence: 99%

“…Anemia of CKD is associated with decreased oxygen delivery and utilization, ventricular hypertrophy, congestive heart failure, and decreased cognition and mental acuity (2)(3)(4)(5)(6). Correction of anemia has been shown to improve exercise capacity, health-related quality of life, and cognition, and it may slow the progression of renal disease (7)(8)(9)(10). Since their development, erythropoiesis-stimulating agents (ESAs) have become the standard of care for the treatment of patients with anemia associated with CKD (10,11).…”

mentioning

confidence: 99%

A Randomized Controlled Study of Weekly and Biweekly Dosing of Epoetin Alfa in CKD Patients With Anemia

Pèrgola

Gartenberg

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing.Design, setting, participants, & measurements: 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.Results: Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.Conclusions: Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

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“…One retrospective study (84) and two prospective studies (85,86) suggested that improvement of anemia by treatment with EPO delayed the progression of renal failure.…”

Section: Treatment Targeting Hypoxic Tubulointerstitial Damagementioning

confidence: 99%

Mechanisms of Tubulointerstitial Injury in the Kidney: Final Common Pathways to End-stage Renal Failure

2004

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There are many different glomerular disorders, including glomerulonephritis, diabetic nephropathy, and hypertensive nephrosclerosis. However, once glomerular damage reaches a certain threshold, the progression of renal disease is consistent and irreversible. Recent studies emphasized the crucial role of tubulointerstitial injury as a mediator of progression of kidney disease. One common mechanism that leads to renal failure via tubulointerstitial injury is massive proteinuria. Accumulating evidence suggests critical effects of filtered macromolecules on tubular cells, including lysosomal rupture, energy depletion, and tubular injury directly induced by specific components such as complement components. Another common mechanism is chronic hypoxia in the tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular capillaries, impairing blood flow delivery. Interstitial fibrosis also impairs oxygen diffusion and supply to tubular cells. This induces chronic hypoxia in this compartment, rendering a vicious cycle. Development of novel therapeutic approaches against these final common pathways will enable us to target any types of renal disease. (Internal Medicine 43: 9-17, 2004)

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Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients

Cited by 173 publications

References 16 publications

Lower haemoglobin level and subsequent decline in kidney function in type 2 diabetic adults without clinical albuminuria

Lower haemoglobin level and subsequent decline in kidney function in type 2 diabetic adults without clinical albuminuria

A Randomized Controlled Study of Weekly and Biweekly Dosing of Epoetin Alfa in CKD Patients With Anemia

Mechanisms of Tubulointerstitial Injury in the Kidney: Final Common Pathways to End-stage Renal Failure

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