Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin

Macdougall, Iain C.; Coles, G A; Williams, J. D.; Davies, Mike E.; Hutton, Richard D.; Cochlin, D.Ll.; Lewis, N. P.; Fox, Keith A.A.; Saunders, Matthew J.

doi:10.1016/0140-6736(90)90733-l

Cited by 228 publications

(96 citation statements)

References 21 publications

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“…There is evidence that anemia is associated with reduced physical capacity in the setting of ESRD and that erythropoietin therapy may improve exercise capacity (7)(8)(9). However, these studies were limited by small sample sizes and were in patients with ESRD.…”

Section: Discussionmentioning

confidence: 97%

“…Although a few studies have examined the association of moderate CKD with physical function (4 -6), all have used subjective measures of function that may not accurately reflect objective physical capacity. Anemia is a complication of declining renal function, and other studies have found an association between anemia and physical capacity in individuals with severe renal disease (7)(8)(9)(10)(11). However, the comparative effects of kidney disease and anemia on objective physical function are not known.…”

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confidence: 98%

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Association of Chronic Kidney Disease and Anemia with Physical Capacity

Odden¹,

Whooley

Shlipak

2004

Journal of the American Society of Nephrology

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Abstract. Chronic kidney disease (CKD) and anemia are common conditions in the outpatient setting, but their independent and additive effects on physical capacity have not been well characterized. The association of CKD and anemia with selfreported physical function was evaluated and exercise capacity was measured in patients with coronary disease. A crosssectional study of 954 outpatients enrolled in the Heart and Soul study was performed. CKD was defined as a measured creatinine clearance Ͻ60 ml/min, and anemia was defined as a hemoglobin level of Ͻ12g/dl. Physical function was selfassessed using the physical limitation subscale of the Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD was associated with lower self-reported physical function (67.6 versus 74.9; P Ͻ 0.001) and lower exercise capacity (5.5 versus 7.9; P Ͻ 0.001). Similarly, anemia was associated with lower self-reported physical function (62.6 versus 74.3; P Ͻ 0.001) and exercise capacity (5.7 versus 7.5; P Ͻ 0.001). After multivariate adjustment, CKD (69.4 versus 74.2; P ϭ 0.003) and anemia (67.5 versus 73.6; P ϭ 0.009) each remained associated with lower mean self-reported physical function. In addition, patients with CKD (6.3 versus 7.7; P Ͻ 0.001) or anemia (6.5 versus 7.4; P ϭ 0.004) had lower adjusted mean exercise capacities. Participants with both CKD and anemia had lower self-reported physical function and exercise capacity than those with either alone.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 98%

Association of Chronic Kidney Disease and Anemia with Physical Capacity

Odden¹,

Whooley

Shlipak

2004

Journal of the American Society of Nephrology

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“…Both uncontrolled (30,31) and controlled (14) studies have shown that partial correction of anemia leads to partial regression of LVH in dialysis patients, in addition to improving QOL and physical performance (12,13). Three controlled studies of normalization of hemoglobin with erythropoietin in hemodialysis populations have been reported to date.…”

Section: Discussionmentioning

confidence: 99%

Double-Blind Comparison of Full and Partial Anemia Correction in Incident Hemodialysis Patients without Symptomatic Heart Disease

Parfrey¹,

Foley²,

Wittreich³

et al. 2005

Journal of the American Society of Nephrology

338

302

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It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation. In this randomized, double-blind study, lower (9.5 to 11.5 g/dl) and higher (13.5 to 14.5 g/dl) hemoglobin targets were generated with epoetin ␣ over 24 wk and maintained for an additional 72 wk. Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation. The primary outcome measure was left ventricular volume index (LVVI). The study enrolled 596 patients. Mean age, duration of dialysis therapy, baseline predialysis hemoglobin, and LVVI were 50.8 yr, 0.8 yr, 11.0 g/dl, and 69 ml/m 2 , respectively; 18% had diabetic nephropathy. Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl, respectively, at 24 wk. Percentage changes in LVVI between baseline and last value were similar (7.6% in the higher and 8.3% in the lower target group) as were the changes in left ventricular mass index (16.8 versus 14.2%). For the secondary outcomes, the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group (1.21 versus ؊2.31; P ‫؍‬ 0.036). Overall adverse event rates were similar in both target groups; higher (P < 0.05) rates of skeletal pain, surgery, and dizziness were seen in the lower target group, and headache and cerebrovascular events were seen in the higher target group. Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure, compared with partial correction.

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“…London et al (11) showed in a miniscule trial of just 11 hemodialysis patients, over no more than 6 months of rHuEPO, that partial correction of severe anemia led to reduced LV cavity volume, left atrial volume, and LV mass index, using primitive (by today's standards) echocardiographic techniques. MacDougall et al (12) studied just 10 hemodialysis patients, albeit more comprehensively, and for longer (12 months), and, again, with substantial but incomplete correction of profound anemia, there were salutary changes in many cardiorespiratory parameters.…”

Section: What Has Gone Wrong?mentioning

confidence: 99%

2009

Goldsmith¹

2010

Clinical Journal of the American Society of Nephrology

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The recombinant human erythropoietins and allied proteins (epoetin alfa, attempted copies and biosimilar variants of epoetin alfa, epoetin beta, epoetin delta, epoetin zeta, epoetin theta, epoetin omega, darbepoetin alfa, and methoxy-polyethylene glycol-epoetin beta) are among the most successful and earliest examples of biotechnologically manufactured products to be used in clinical medicine. This article charts a brief history of their use in clinical medicine, mainly dealing with chronic kidney disease, paying special attention to how these agents were introduced into clinical medicine and what has happened subsequently; in 2009, there were several developments that could be regarded as a "perfect storm" in terms of the long-term use of these compounds in chronic kidney disease and oncology and, likely, elsewhere. We are now very much at a "crossroads," where mature reflection is required, because with the latest trials and meta-analyses, these therapies seem not only expensive but also very much a clinical tradeoff (increased risk of adverse effects versus a small gain in fatigue scores). How we arrived at this crossroads is a useful illustration of how easy it is, without properly designed randomized, controlled trials, to assume that clinical benefit must follow therapeutic interventions.Clin J Am Soc Nephrol 5: 929 -935, 2010.

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Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin

Cited by 228 publications

References 21 publications

Association of Chronic Kidney Disease and Anemia with Physical Capacity

Association of Chronic Kidney Disease and Anemia with Physical Capacity

Double-Blind Comparison of Full and Partial Anemia Correction in Incident Hemodialysis Patients without Symptomatic Heart Disease

2009

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