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: U.S. children on peritoneal dialysis with Hb levels of ≥11 g/dl were less likely to be hospitalized but had no observed difference in mortality, while higher ESA doses were associated with an increased risk of both hospitalization and mortality.
Abstract: Clinical practice guidelines for management of anemia in children with end-stage kidney disease (ESKD) remain largely opinion-based. In this study, we evaluated the risk of mortality and hospitalization by hemoglobin (Hb) level in a large prevalent population of U.S. children on peritoneal dialysis (PD). Hemoglobin levels in prevalent PD patients from the 2005 End Stage Renal Disease Clinical Performance Measures Project were linked with 5-year mortality and 4-year hospitalization records from the United States Renal Data System. Of the 468 patients included in the study, the mean age was 11 years, 55 % were male, 67 % were white, 254 (54 %) were hospitalized, and 23 (5 %) died. Median (interquartile range) Hb levels were 11.7 (10.7–12.6) g/dl, and 30 % had Hb levels of <11 g/dl. In adjusted survival analysis, Hb thresholds of 10, 11, or 12 g/dl were not associated with a significant difference in risk of death. The incidence rate ratio (IRR) of hospitalization for patients with a mean Hb of ≥11 g/dl was 0.56 (95 % CI 0.43–0.73). Compared to a reference range of Hb of 11 to <12, Hb of ≥12 g/dl was not associated with a significant difference in hospitalization risk (IRR 0.88; 95 % CI 0.61–1.25). Using age- and sex specific cut-offs for anemia, children who were not anemic had a 27 % decreased risk of hospitalization compared to those with anemia (IRR 0.73; 95 % CI 0.55–0.97). Compared to the first erythropoiesis stimulating agent (ESA) dosing quartile, higher ESA doses were associated with an increased risk of both hospitalization and mortality. U.S. children on PD with Hb levels of ≥11 g/dl were less likely to be hospitalized but had no observed difference in mortality. Children who were not anemic were also less likely to be hospitalized. Further study is necessary to elucidate whether a single optimal Hb level or a range applies to the pediatric ESKD population.
10 citations
TL;DR: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb and the CERA dose requirement decreased significantly, suggesting the conversion ratio may need to be reduced.
Abstract: Background: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin β (CERA) in pre-dialysis chronic kidney disease (CKD) patients. Methods: Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-β, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. Results: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P P=N-S). Conclusion: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment.
9 citations
TL;DR: There is enough data that shows high mortality after percutaneous transluminal coronary angioplasty in patients with reduced renal function and that slight renal dysfunction exposes the patient with a cardiac event to an excessive cardiac mortality.
Abstract: This review focuses on the association between renal insufficiency and cardiovascular disease and discusses therapeutic options. Although the association of chronic renal insufficiency and cardiovascular risk was first shown in patients with end-stage renal disease, even minor renal dysfunction has now been established as an independent risk for atherosclerotic cardiovascular disease. Treatment with angiotensin-converting enzyme inhibitors and statins can reduce cardiovascular morbidity and mortality in patients with renal insufficiency. Coronary revascularization improves the prognosis in patients with renal dysfunction, but there is still an underutilization of coronary revascularization procedures in patients with renal insufficiency. There is enough data that shows high mortality after percutaneous transluminal coronary angioplasty in patients with reduced renal function and that slight renal dysfunction exposes the patient with a cardiac event to an excessive cardiac mortality. Further investigation should focus on the cause of and possible preventive interventions, for the staggering cardiovascular risk in the ever-increasing number of people with renal dysfunction.
9 citations
Cites background from "Effects of haemoglobin normalizatio..."
...Presently, the available data strongly suggest that appropriately managed anemia reduces cardiac morbidity and possible mortality [6, 45, 46] and it seems reasonable to aggressively treat anemia to obtain hemoglobin values in the Kidney Disease Outcome Quality Initiative (K/DOQI) target range of 11–12 gm/dl....
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TL;DR: Although both groups had a rise in Hgb level post-dialysis, group 2 patients had a rises in %ΔHgb that was greater than the relatively small difference in%ΔBW between the 2 groups, and the r2 of 0.24 suggests that only 25% of the variability found in % ΔHgb can be related to %� ΔBW.
Abstract: OBJECTIVE
The objective of this study was to compare pre-dialysis and post-dialysis hemoglobin (Hgb) and ultrafiltration in hemodialysis patients. Factors influencing Hgb are not well understood.
METHODS
Pre-dialysis and post-dialysis Hgb and weight were measured in 133 hemodialysis patients. Absolute and percentage change in Hgb (%ΔHgb) and percent change in body weight (%ΔBW) were determined for that treatment. Patients were divided into 2 groups, those with post-dialysis Hgb < 13 g/dL (group 1) and those with post-dialysis Hgb ≥13 g/dL (group 2); the differences in %ΔBW were compared between the 2 groups.
RESULTS
The mean pre-dialysis Hgb was 11.9 ± 1.4 g/dL, the mean post-dialysis Hgb level was 12.8 ± 1.8 g/dL. The %ΔHgb was 3.9 ± 6.6 in group 1 and 10.8 ± 7.8 in group 2. The %ΔBW was 3.1 ± 1.4 in group 1 and 3.9 ± 1.7 in group 2 (p < .001 for all comparisons). We found that although both groups had a rise in Hgb level post-dialysis, group 2 patients had a rise in %ΔHgb that was greater than the relatively small difference in %ΔBW between the 2 groups. In addition, we found only a modest correlation between %ΔBW and %ΔHgb in both groups. The r2 of 0.24 suggests that only 25% of the variability found in %ΔHgb can be related to %ΔBW.
CONCLUSIONS
Patients with post-dialysis Hgb ≥13 g/dL had a greater increase in %ΔHgb that was out of proportion to %ΔBW. Factors other than %ΔBW may play a role in determining post-dialysis Hgb.
9 citations
TL;DR: The interplay of multiple risk factors in diabetic patients with ESRD demands a multidisciplinary approach for the early identification and management of cardiovascular risk factors – hypercholsterolaemia, hypertension, blood glucose and anaemia – in order to optimise outcomes in these patients.
Abstract: Patients with diabetes represent an increasing proportion of end-stage renal disease (ESRD) patients. Cardiovascular risk, already formidable among patients on dialysis, is significantly higher among those who also have diabetes. Diabetic ESRD patients are not only at higher risk of ischaemic events, but are also subject to haemodynamic overload, because of anaemia, hypertension, and arteriovenous dialysis connections. Mortality rates are also significantly higher in these patients. Hypertension an anaemia stand out as opportunities for intervention in these patients. Anaemia per se is associated with an increased risk of cardiovascular abnormalities, including left ventricular hypertrophy, and with an increased risk of mortality. The interplay of multiple risk factors in diabetic patients with ESRD demands a multidisciplinary approach for the early identification and management of cardiovascular risk factors – hypercholsterolaemia, hypertension, blood glucose and anaemia – in order to optimise outcomes in these patients.
9 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