losartan-potassium and Peripheral-Vascular-Diseases

Anaemia is a frequent complication of diabetic nephropathy. It has only recently been recognised that in diabetic patients anaemia is seen not only in preterminal renal failure, but also frequently in patients with only minor derangement of renal function. At any level of glomerular filtration rate (GFR) anaemia is more frequent and severe in diabetic compared to nondiabetic patients. A major cause of anaemia is an inappropriate response of erythropoietin to anaemia. Additional factors are iron deficiency and iatrogenic factors, e.g. ACE inhibitor treatment. When serum creatinine is still normal, the erythropoietin concentration is predictive of more rapid loss of glomerular function. When serum creatinine is elevated, the haemoglobin values are predictive of the rate of progression. It is currently under investigation whether reversal of anaemia attenuates the rate of progression. Because most of the late complications of diabetes (retinopathy, neuropathy, heart disease, peripheral arterial disease) involve ischaemic tissue damage, it would be intuitively plausible that treatment with human recombinant erythropoietin should be beneficial, but definite evidence for this hypothesis is currently not available.

Topics: Anemia; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Erythrocytes, Abnormal; Erythropoietin; Heart Failure; Humans; Kidney Failure, Chronic; Myocardial Ischemia; Peripheral Vascular Diseases

We hypothesized that erythropoietin (EPO)-immersed gelatin hydrogel microspheres (GHM) injected into ischemic legs might continuously release a small amount of EPO to locally stimulate angiogenesis without unfavorable systemic effects.. EPO is a potent angiogenic factor, but its use for relieving ischemic organs is limited because of the untoward systemic erythrogenic effect and its short half-life in plasma.. The right femoral arteries of BALB/c mice were ligated. Recombinant human EPO (5,000 IU/kg)-immersed GHM was injected into the right hind limb muscles (n = 12); the control groups included a saline-injected group (n = 12), an EPO-injected group (n = 8), and an empty GHM-injected group (n = 8).. Eight weeks later, improvement of blood perfusion to the ischemic limb was significantly augmented in the EPO-GHM group compared with any of the control groups. There was no increase in the hemoglobin level, nor was there any increase in endothelial progenitor cells. However, capillary and arteriolar densities were significantly increased in this group. Although the treatment did not affect the levels of vascular endothelial growth factor or interleukin-1 beta, it up-regulated the EPO receptor and matrix metalloproteinase-2 and activated the downstream signaling of Akt and also endothelial nitric oxide synthase in ischemic limbs, which might have been associated with the evident angiogenic and arteriogenic effects in the present system.. The present drug delivery system is suggested to have potential as a novel noninvasive therapy for ischemic peripheral artery disease.

Topics: Adult Stem Cells; Angiogenesis Inducing Agents; Animals; Cells, Cultured; Delayed-Action Preparations; Endothelial Cells; Erythropoietin; Hydrogels; Ischemia; Lower Extremity; Male; Mice; Mice, Inbred BALB C; Microspheres; Myocytes, Smooth Muscle; Neovascularization, Physiologic; Peripheral Vascular Diseases; Receptors, Erythropoietin; Recombinant Proteins; Regional Blood Flow

Systemic hypertension may develop, or worsen, in 20-30% of haemodialysis patients treated with recombinant human erythropoietin (r-HuEPO). No particular group of patients, however, should be excluded from r-HuEPO treatment because of this increased risk. In the vast majority of cases, hypertension can be managed effectively by reducing dry weight, and by adding an antihypertensive agent if necessary. Only if these approaches are ineffective should the dose of r-HuEPO be reduced. Patients on dialysis are likely to be intolerant of cardiac ischaemia, as a result of coronary artery disease, microvascular occlusive disease, inadequate neo-vascularization in cardiac hypertrophy, or reduced glucose uptake (which impairs non-oxidative metabolism of the heart). Treatment with r-HuEPO can significantly reduce cardiac risk, as measured by surrogate endpoints such as left ventricular hypertrophy. More studies are urgently needed to investigate the potential beneficial effects of r-HuEPO on hard endpoints such as cardiac morbidity and mortality. In addition, dose-response data for target haematocrits in the range 30-40% are needed before an appropriate target haematocrit can be determined for patients with symptomatic vascular and cardiac disease.

Topics: Erythropoietin; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardial Ischemia; Peripheral Vascular Diseases; Recombinant Proteins