Giacobbe Ms

Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy

3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors are established drugs for the treatment of hypercholesterolemia, but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering. Moreover, in experimental models of progressive renal disease, statins have reduced the extent of glomerulosclerosis. This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy, stable renal function, and no indicators of poor long‐term prognosis. The effects of therapy were evaluated on the basis of 24‐hour proteinuria (total proteinuria and albuminuria), albuminemia, creatinine clearance, cholesterol, and triglyceride values. Renal function remained stable in all patients. A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations. An increase in serum albumin was observed after 6 months of therapy. This study suggests that there is an antiproteinuric effect of HMG‐CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy. (Clin Pharmacol Ther 2000;67:427‐31.)

Effects of lisinopril administration on blood bcl‐2 concentrations in patients with immunoglobulin A nephropathy

We evaluated blood concentrations of bcl‐2, a proto‐oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl‐2 were higher in patients with proteinuria than in those without proteinuria. A 6‐month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl‐2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl‐2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin‐converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.

From the Oxygen to the Organ Protection: Erythropoietin as Protagonist in Internal Medicine

Erythropoietin (EPO), already known as the stimulating hormone for erythropoiesis, has shown different and interesting pleiotropic actions. It does not only affect erythroid cells, but also myeloid cells, lymphocytes and megakaryocytes. This hormone can also enhance phagocytic function of the polymorphonuclear cells and reduce the activation of macrophages, thus modulating the inflammatory process.Moreover, hematopoietic and endothelial cells probably have the same cellular origin, and the discovery of erythropoietin receptors (EPO-R) also on mesangial and myocardial cells, smooth muscle fibrocells and neurons has prompted the study of the non-erythropoietic functions of this hormone.The interaction between EPO and VEGF may be of particular importance in neovascularization and wound healing. Different studies have demonstrated that EPO has an important direct hemodynamic and vasoactive action, which does not depend exclusively on any increase in hematocrit and viscosity. Moreover EPO showed protective effects on myocardial cells against apoptosis induced by ischemia/repefusion injury, but it could negatively affect pulmonary hypertension in patient with chronic cor pulmonale.This review aims to stress the importance of the increasing interest in EPO applications and the necessity of further studies to gain a deeper knowledge of this hormone and its pleiotropic and complex actions.

The influence of hypercholesterolemia on some aspects of immune pattern in the elderly.

In order to investigate if age related dislipidemia was associated with immunological changes in vivo, humoral, soluble and cellular immune parameters were evaluated both in elderly with and without hypercholesterolemia and in young adults. Significantly increased IgG and IgA values were found in hypercholesterolemic aged compared to the other groups. Increased plasma neopterin levels (a pteridine generally used as a marker of macrophage activity) were reported in healthy aged subjects, whereas a lesser degree of the activation of the macrophage system was found in the hypercholesterolemic aged subjects. Compared with the young controls, an increase of interleukin 2 receptor expressing cells and of the IL-2 soluble receptors was noticeable in healthy aged subjects, whereas in hypercholesterolemic aged subjects only a minor increase of the IL-2 membrane receptor was noticed. We suggest that hypercholesterolemia may play a role in immune function in aging.