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

Abstract

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-

Chronic kidney disease, heart failure and anemia

“…However, on balance, among randomized controlled trials of dialysis patients, there has been no demonstration of an impact of normalization of Hgb with ESA on CVD events or survival (20)(21)(22)(23)(24)(25); moreover, many of these studies have raised questions of harm (vascular access thrombosis and stroke), which have not been definitively addressed. Smaller randomized trials among nondialysis patients have also failed to show improvements in surrogate end points for CV outcomes (left ventricular mass index on echocardiography and decline in GFR) among ESA-treated patients (26)(27)(28)(29). Recent larger randomized clinical trials have had variable and somewhat conflicting results.…”

Anemia and Cardiovascular Risk

“…Beginning with the clear association between higher Hb levels and better outcomes and the hypothesis that this may be due to the deleterious effect of anemia on the development of LVH or simply a marker of greater morbidity (mainly inflammation), a number of clinical studies were designed to test whether correcting anemia can reverse LVH and improve patient outcomes. Taking LVH as an intermediate outcome rather than a surrogate end point, data from mainly small and uncontrolled studies indicated that correcting anemia led to partial LVH regression (16 -20), but larger randomized studies failed to confirm that randomization to the higher Hb levels that were obtained using recombinant human erythropoietin had a significant positive effect on patients who were not (21,22) and were (23) on dialysis.…”

Use of agents stimulating erythropoiesis in digestive diseases

“…The clinical benefits and adverse effects associated with normal or near normal hemoglobin values were evaluated in multiple randomized studies that assessed mortality and morbidity from cardiovascular or cerebrovascular events, good control of blood pressure, quality of life, functional status and vascular access thrombosis [71,[118][119][120][121][122][123][124][125][126] . The results of these studies have not suggested any improvements after correction of anemia, except in quality of life.…”