Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end‐stage renal failure

197

115

Abstract. It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin ␣ as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 Ϯ 9 to 121 Ϯ 14 g/L, mean Ϯ SD) and decreased for group B (from 112 Ϯ 8 to 108 Ϯ 13 g/L) (P Ͻ 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 Ϯ 20 g/m 2 for group A versus 4.5 Ϯ 20 g/m 2 for group B, P ϭ NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 Ϯ 14 versus 138 Ϯ 13 mmHg) or diastolic BP (80 Ϯ 6 versus 79 Ϯ 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 Ϯ 9 versus 6 Ϯ 8 ml/min per 1.73 m 2 ). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.Chronic kidney disease (CKD) is widespread in the community, with a prevalence far exceeding previous estimates (1). Many studies examining mortality and morbidity rates among patients with CKD have identified high rates of cardiovascular events. When even mild renal insufficiency is associated with other risk factors for cardiovascular disease, the risk of subsequent cardiovascular events is significantly increased (2-10). The effect of mild renal insufficiency (serum creatinine levels of Ͼ124 M) on cardiovascular risk is possibly also independent of other known risk factors and treatment (11)(12)(13)(14)(15). For patients established on dialysis, cardiovascular disease is responsible for up to 50% of the all-cause mortality rate (16,17). It is therefore important to attempt to reduce the incidence of cardiovascular events with risk factor modification before the onset of dialysis.Left ventricular (LV) hypertrophy (LVH) is recognized as a powerful independent predictor of death and morbidity in the dialysis population, together with anemia, hypertension, malnutrition, hyperparathyroidism, and an elevated calcium-phos-

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Effects of Early and Late Intervention with Epoetin α on Left Ventricular Mass among Patients with Chronic Kidney Disease (Stage 3 or 4)

Roger¹,

McMahon²,

Clarkson³

et al. 2004

197

115

“…Another study used a double-blind crossover design to compare hemoglobin targets of 10 and 14 g/dl, each applied for 6 wk; the higher target led to reduced cardiac output and improved QOL (21).…”

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

341

302

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.

“…Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis, [1][2][3] interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis. [4][5][6] This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesisstimulating agents (ESAs).…”

mentioning

confidence: 99%

Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Borzych-Dużałka

Bilginer

et al. 2013

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (,10 g/dl or ,9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.