Biomedical subjects

Alessandro Fornasieri

Publications and source records attributed to Alessandro Fornasieri.

3 recordsLinked to original sources

PubMed2007

Multicenter study on hepatitis C virus-related cryoglobulinemic glomerulonephritis.

BACKGROUND: Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key factor affecting prognosis. METHODS: Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. RESULTS: Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mkappa [IgMkappa]/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 mumol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. CONCLUSION: Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past.

Adult↗

PubMed2006

Glomerular podocytes contain neuron-like functional synaptic vesicles.

Although patients with chronic renal failure are increasing worldwide, many aspects of kidney biology remain to be elucidated. Recent research has uncovered several molecular properties of the glomerular filtration barrier, in which podocytes, highly differentiated, ramified cells that enwrap the glomerular basement membrane, have been reported to be mainly responsible for filter's selectivity. We previously described that podocytes express Rab3A, a GTPase restricted to cell types that are capable of highly regulated exocytosis, such as neuronal cells. Here, we first demonstrate by a proteomic study that Rab3A in podocytes coimmmunoprecipitates with molecules once thought to be synapse specific. We then show that podocytes possess structures resembling synaptic vesicles, which contain glutamate, coexpress Rab3A and synaptotagmin 1, and undergo spontaneous and stimulated exocytosis and recycling, with glutamate release. Finally, from the results of a cDNA microarray study, we describe the presence of a series of neuron- and synapse-specific molecules in normal human glomeruli and confirm the glomerular protein expression of both metabotropic and ionotropic glutamate receptors. These data point toward a synaptic-like mechanism of communication among glomerular cells, which perfectly fits with the molecular composition of the glomerular filter and puts in perspective several previous observations, proposing a different working hypothesis for understanding glomerular signaling dynamics.

Animals↗

PubMedDate not supplied

Circulating antibodies recognising oxidatively-modified low-density lipoproteins in patients with IgA nephropathy, membranous glomerulonephritis and focal glomerulosclerosis.

BACKGROUND: Oxidation of low-density lipoproteins (LDL) generates molecular epitopes that play a pathologic role in experimental glomerular diseases and can also elicit an immune response and the generation of anti-oxidatively-modified LDL antibodies. METHODS: We investigated, for the first time in humans, the enhanced induction of LDL oxidation in chronic glomerulonephritis, the presence of circulating antibodies against oxidatively-modified LDL in patients with IgA glomerulonephritis (IgA GN) or with nephrotic syndrome associated with focal glomerulosclerosis (FGS) and primary membranous glomerulonephritis (MGN). The antibody levels were measured by enzyme-linked immunosorbent assay (ELISA) using native and copper-, peroxidase-, hypochlorite-, and peroxynitrite-oxidized LDL. RESULTS: Compared to control subjects, the three groups of patients, particularly the IgA GN patients, had higher serum levels of antibodies recognising LDL oxidised with the four different modalities and higher concentrations of cholesterol in circulating immune complexes. None of these were significantly correlated with any demographic, histological or biochemical laboratory finding. In patients with IgAGN, we investigated the possible confounding effects of cardiovascular risk factors (hypercholesterolemia, hypertension, diabetes and overt atherosclerosis). Although the concentration of cholesterol in circulating immune complexes was significantly higher in patients with cardiovascular risk factors, no significant differences were observed in the level of anti-oxidised-LDL antibodies. This analysis, however, was impossible in FGS and MGN patients because of the high prevalence of hypercholesterolemia in these groups. CONCLUSIONS: These results suggest that IgA GN, MGN and FGS are associated with an enhanced immune response to LDL oxidised with different stimuli mimicking the pro-oxidant environment occurring in vivo, mirrored by the increased levels of specific antibodies, very likely linked to enhanced in vivo LDL oxidation which might participate in glomerular damage and progression.

Adult↗