Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end‐stage renal failure
01 Sep 2000-Nephrology Dialysis Transplantation (Oxford University Press)-Vol. 15, Iss: 9, pp 1425-1430
TL;DR: There may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [Hb] in haemodialysis patients, and a substantially higher dose of epoetin is required to maintain this level.
Abstract: BACKGROUND: The optimal haemoglobin concentration ([Hb]) for patients with end-stage renal failure is uncertain. In particular, it is unclear whether Hb normalization may be an advantage to such patients who are otherwise well. METHODS: A prospective, randomized, double-blind cross-over study was completed in 14 haemodialysis patients (12 male) aged between 23 and 65 years over a period of 18 months, using a variety of measures to examine the effect of epoetin at target [Hb] of 10 g/dl ([Hb](10)) and 14 g/dl ([Hb](14)). Patients were randomized to maintain one or other of the target levels for 6 weeks before being crossed over to the alternative [Hb]. Baseline data (mean [Hb]: 8.5+/-0.2 g/dl) were also included selectively. Six patients were known to be hypertensive. Comparisons were made between 24-h ambulatory blood pressure levels (ABP), echocardiographic findings and estimates of blood volume (BV), plasma volume (PV) and Hb mass. Quality of life estimates were obtained using the Sickness Impact Profile (SIP), and epoetin dosage requirements at target [Hb] were assessed. RESULTS: Daytime and nocturnal ABP (systolic and diastolic) were not different at the respective target [Hb], although nocturnal diastolic levels were higher compared with baseline (73+/-4 mmHg) at both [Hb](10) (83+/-3, P:<0.01) and [Hb](14) (81+/-6, P:<0.05). Significant reductions in cardiac output (5.2+/-0.3 vs 6.6+/-0.5 l/min, P:<0.01) and left ventricular end-diastolic diameter (4.8+/-0.2 vs 5.2+/-0.2 cm, P:<0. 001) were found at [Hb](14) compared with [Hb](10). Left ventricular mass index was correlated with both PV (P:<0.001) and BV (P:<0.01), but not with Hb mass. The PV decreased as the [Hb] rose (P:<0.001) but BV remained unchanged. Quality of life was significantly improved at [Hb](14) compared with [Hb](10) for both total score (6. 5+/-1.7 vs 13.4+/-3.0, P:=0.01) and psychosocial dimension score (5. 4+/-1.9 vs 15.4+/-4.0, P:<0.01). The maintenance weekly dose of epoetin required was 80% higher at [Hb](14) compared with [Hb](10) (P:<0.001). CONCLUSION: These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [Hb] in haemodialysis patients. Although untoward effects were not identified in this study at [Hb](14), a substantially higher dose of epoetin is required to maintain this level.
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TL;DR: There is a triangular relationship, a vicious circle, between CHF, CKI and anemia where each of these three can both cause and be caused by the other.
Abstract: Anemia is seen in chronic kidney insufficiency (CKI), dialysis patients, congestive heart failure (CHF), and renal transplantation. Anemia can lead to progressive cardiac damage as well as progressive renal damage. It is not generally appreciated that CHF itself may be a very common contributor to both the production of anemia as well as to the progression of the renal failure. Correction of the anemia with erythropoietin and, as necessary, intravenous iron, may prevent the deterioration of both the heart and the kidneys. We suggest that there is a triangular relationship, a vicious circle, between CHF, CKI and anemia where each of these three can both cause and be caused by the other. We call this syndrome the cardio-renal anemia (CRA) syndrome. All physicians, especially cardiologists and internists who treat CKI and CHF, should be made aware of the dangers of anemia in CKI and CHF and should work with nephrologists to correct it.
23 citations
TL;DR: Pre-dialysis rHuEPO confers a survival benefit that depends on achieved hematocrit and diminishes post- dialysis, but is independent of several surrogates for quality of care except for insurance status pre-ESRD.
Abstract: Background: Recombinant human erythropoietin (rHuEPO) is recommended pre-dialysis to correct the anemia of chronic kidney disease. This study evaluated the impact of pre-dialysis rH
22 citations
01 Jan 2004
TL;DR: The burden of illness due to cardiac disease in chronic uremia is high and the prevalence of clinical manifestations of cardiac disease on initiation of end-stage renal disease (ESRD) therapy is high.
Abstract: The burden of illness due to cardiac disease in chronic uremia is high. The cardiac death rate has been reported as 104/1000 patient-years in the USA, and cardiac disease accounted for 45% of all deaths (1). When compared to the general population the annual cardiovascular death rate for dialysis patients is substantially higher in all age groups, particularly at younger ages (Figure 1) (2). Indices of morbidity are also high. The prevalence of clinical manifestations of cardiac disease on initiation of end-stage renal disease (ESRD) therapy is high (3–5) (Table 1). The probability of having a myocardial infarction or angina requiring hospitalization in hemodialysis patients is 10% per year (6).
21 citations
TL;DR: A case is presented that underscores the need to consider the study design when reviewing the data at a population level in order to determine what is most appropriate for the authors' patient, and how to correct anemia in CKD patients.
Abstract: Anemia is common in chronic kidney disease (CKD) due to a state of erythropoietin deficiency. Erythropoietin therapy has been used for approximately 20 years to correct anemia in CKD and to improve both subjective and objective outcomes. Guidelines that establish a hemoglobin (Hb) goal for anemia correction in CKD patients are largely based on observational data. Controversy still exists, however, because outcomes have not been consistent with various degrees of anemia correction. The number of prospective randomized trials investigating the effects of anemia correction on cardiovascular (CV) morbidity and mortality in CKD patients, an already high-risk group, is limited. With respect to improving CV outcomes in the CKD population, the currently available trial data caution against raising Hb levels in CKD patients to approach more "normal" physiologic ranges. The disappointing experience with the trial data must be weighed against the beneficial associations of erythropoietin therapy that have been generated from observational data. Establishing the ideal target Hb ranges for anemia correction in CKD patients remains a dynamic process and leaves many gray areas to be further elucidated. Here, we present a case that underscores the need to consider the study design when reviewing the data at a population level in order to determine what is most appropriate for our patient.
21 citations
TL;DR: Results from large-scale clinical trials are required to clarify the effects of early anaemia correction on mortality and cardiovascular function, as well as appropriate treatment targets in different patient populations, to extend patient survival through cardioprotective effects.
Abstract: Cardiovascular disease is the major cause of death among patients with end-stage renal disease, accounting for almost half of all fatalities. In recent years much progress has been made in understanding the pathogenesis of cardiovascular disease in the uraemic population. Anaemia is a consistent finding in chronic renal disease, affecting up to 90% of patients, and the central role of anaemia in the development of cardiovascular dysfunction is now well established. A significant proportion of patients have established cardiovascular complications on initiation of dialysis, raising the possibility of early correction of anaemia as a strategy for preventing cardiovascular co-morbidities among renal patients. Randomized, controlled trials have shown that normalization of haemoglobin (Hb) with recombinant erythropoietin (rh-Epo) is of no cardiovascular benefit in haemodialysis patients with symptomatic heart failure, ischaemic heart disease, or severe left ventricular dilatation, although suggestive evidence exists for benefits at earlier stages of cardiac disease. Results from large-scale clinical trials are required to clarify the effects of early anaemia correction on mortality and cardiovascular function, as well as appropriate treatment targets in different patient populations. The potential exists for higher Hb levels to extend patient survival through cardioprotective effects.
20 citations
References
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TL;DR: In this article, the authors developed the Sickness Impact Profile (SIP), a behaviorally based measure of health status, and evaluated its reliability and validity using multitrait-multimethod technique.
Abstract: The final development of the Sickness Impact Profile (SIP), a behaviorally based measure of health status, is presented. A large field trial on a random sample of prepaid group practice enrollees and smaller trials on samples of patients with hyperthyroidism, rheumatoid arthritis and hip replacements were undertaken to assess reliability and validity of the SIP and provide data for category and item analyses. Test-retest reliability (r = 0.92) and internal consistency (r - 0.94) were high. Convergent and discriminant validity was evaluated using the multitrait--multimethod technique. Clinical validity was assessed by determining the relationship between clinical measures of disease and the SIP scores. The relationship between the SIP and criterion measures were moderate to high and in the direction hypothesized. A technique for describing and assessing similarities and differences among groups was developed using profile and pattern analysis. The final SIP contains 136 items in 12 categories. Overall, category, and dimension scores may be calculated.
4,283 citations
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01 Feb 1994
TL;DR: In this paper, the principles of exercise testing and interpretation are presented for exercise testing in the Libros de Medicina (Patologia) 5/e - Patologia - 139,00
Abstract: Principles of Exercise Testing and Interpretation, 5/e - Libros de Medicina - Patologia - 139,00
2,331 citations
TL;DR: In patients with clinically evident congestive heart failure or ischemic heart disease who are receiving hemodialysis, administration of epoetin to raise their hematocrit to 42 percent is not recommended.
Abstract: Background In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis. Methods We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis: 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent, and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study. The median duration of treatment was 14 months. The primary end point was the length of time to death or a first nonfatal myocardial infarction. Results After 29 months, there were 183 deaths and 19 first nonfatal myocardial infarctions among the patients in the normal-hematocrit group and 150 deat...
1,944 citations
TL;DR: It is concluded that clinical and echocardiographic cardiovascular disease are already present in a very high proportion of patients starting ESRD therapy and are independent mortality factors.
1,255 citations
TL;DR: Overstretching appears to be coupled with oxidant stress, expression of Fas, programmed cell death, architectural rearrangement of myocytes, and impairment in force development of the myocardium.
Abstract: To determine the effects of loading on active and passive tensions, programmed cell death, superoxide anion formation, the expression of Fas on myocytes, and side-to-side slippage of myocytes, papillary muscles were exposed to 7-8 and 50 mN/mm2 and these parameters were measured over a 3-h period. Overstretching produced a 21- and a 2.4-fold increase in apoptotic myocyte and nonmyocyte cell death, respectively. Concurrently, the generation of reactive oxygen species increased 2.4-fold and the number of myocytes labeled by Fas protein 21-fold. Moreover, a 15% decrease in the number of myocytes included in the thickness of the papillary muscle was found in combination with a 7% decrease in sarcomere length and the inability of muscles to maintain stable levels of passive and active tensions. The addition of the NO-releasing drug, C87-3754, prevented superoxide anion formation, programmed cell death, and the alterations in active and passive tensions with time of overloaded papillary muscles. In conclusion, overstretching appears to be coupled with oxidant stress, expression of Fas, programmed cell death, architectural rearrangement of myocytes, and impairment in force development of the myocardium.
642 citations