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Biomedical subjects

M Carraro

Publications and source records attributed to M Carraro.

At least 19 recordsLinked to original sources
PubMed2006

Posttransplant recurrence of proteinuria in a case of focal segmental glomerulosclerosis associated with WT1 mutation.

Posttransplant recurrence of inherited focal segmental glomerulosclerosis (FSGS) is still an enigma owing to the evident paradox of the molecular origin of proteinuria. A young girl with FSGS for WT1 mutation (IVS9+4C>T) and Frasier syndrome received a renal transplant at the age of 11 years. After an initial good outcome with recovery of renal function, proteinuria re-appeared after 7 days and steadily increased up to a nephrotic range. Determination of plasma permeability activity showed concomitant high Palb (0.7). At this point, plasmapheresis was started and after nine cycles with 1500 mL exchange and albumin re-infusion, proteinuria decreased to normal range and is still normal after 3 years. This is the first description of posttransplant recurrence of proteinuria in Frasier syndrome that should be included in potential outcome of renal transplant in this category of patients. This observation confirms the concept that recurrence of proteinuria may occur in inherited forms of FSGS so far reported only for patients carrying NPHS2 mutations and reinforces the idea on multifactorial origin of the disease.

Adolescent↗
PubMed2005

Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome (iNS) with resistance or dependence to steroids is a common disease in children but in spite of an increasing clinical impact its pathogenesis is unknown. We screened for the presence of circulating antibodies against glomerular (podocytes, mesangium) and tubular cells (tubular epithelia) a cohort of 60 children with iNS including 8 patients with a familial trait of iNS or with proven mutation of NPHS1-NPHS2 and 12 with good sensitivity to steroids. Positive sera were found in 8 cases, all belonging to the category without familial trait/molecular defects. The targets of antibodies were characterized with Western blot and MALDI-Mass utilizing beta-hexyl cell extracts separated with two-dimensional electrophoresis. In all cases antibodies of the IgM class were directed against ATP synthase beta chain alone (4 cases) or in combination with actin (3 cases); one child presented IgG against aldose reductase. The clinical picture was nephrotic syndrome with steroid resistance or dependence and variable cyclosporin sensitivity; 3 patients developed end stage renal failure. The basic pathology picture was focal segmental glomerulosclerosis (FSGS) in 4 cases and mesangial proliferative glomerulonephrites with deposition of IgM in 2. Overall, patients with circulating auto-antibodies could not be readely differentiated on clinical grounds with the exception of 3 children who developed positivity for antinuclear antibodies during the follow-up. Affinity-purified IgM from one patient who underwent plasmapheresis for therapeutical pourposes (but not from a normal pool) induced proteinuria in Sprague-Dawley rats and concomitant human IgM deposition within glomeruli. This is the first report of circulating anti-actin/ATP synthase beta chain antibodies in a subset of patients with iNS. Both pathological significance and clinical impact given by the presence of these antibodies and the relationship with other conditions such as lupus-erythematosus, characterized by their presence, must be defined.

Actins↗
PubMed2001

Inhibition of renal permeability towards albumin: a new function of apolipoproteins with possible pathogenetic relevance in focal glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a degenerative renal disease characterized by the accumulation of extracellular matrix and lipids within the glomerular tuft. It has been proposed that an abnormal renal permeabilization towards proteins induced by a putative plasma factor is, in some way, involved in the pathogenesis of the disease. In this paper, we measured the plasma permeability activity (Palb) in several sera of patients with FSGS and found a mean activity of 0.82+/-0.03 which means a marked increase compared to a mean Palb of 0.16+/-0.03 in normal controls. Coincubation of FSGS and normal serum reduced the permeability activity within the normal range; normal serum added to the incubation medium after the glomeruli had already been exposed to the FSGS serum had no effect, suggesting the presence of inhibitory substances with a direct effect on a circulating substrate. Finally, the antipermeability activity was retained when heated to 60 degrees C but not to 100 degrees C. By serial fractionations of normal serum and reported activity measurements at each step, five natural occurring inhibitors of albumin permeabilization were purified and characterized by matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS), as components of apolipoproteins (apo) (apo E2 and E4, apo L, the high Mr apo J and a 28 kDa fragment of apo A-IV). Coincubation of each apolipoprotein with FSGS serum inhibited permeability, but only apo J and apo E2 and E4 were found to be crucial for the process. In conclusion, we have purified from normal serum five inhibitors of permeability induced by FSGS serum, all corresponding to apolipoproteins. An imbalance between permeability factors and apolipoproteins may play a pathogenetic role in FSGS.

Amino Acid Sequence↗
PubMed2001

Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor.

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (P(alb)) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg. kg(-1). day(-1). Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of P(alb) in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced P(alb) significantly in concentration ranges from 10(-6) to 10(-14) mol/l compared with results in control glomeruli. The effect on P(alb) may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the P(alb) defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Vanadium catalyzed reduction of dioxygen to hydrogen peroxide: an oscillating process.

In acid isopropanol/water solution and aerobic conditions, (Bu)4N+VO3- in the presence of an initial amount of H2O2, catalyzes the autoxidation of isopropanol to acetone and the contextual dioxygen reduction to hydrogen peroxide, which accumulates in solution. We have observed that, in the system under examination, the build-up of H2O2 concentration shows an oscillatory behavior. Speciation of the peroxovanadium complexes in iPrOH/H2O has been explored with the combined use of 51V NMR, UV-Vis and ESI-MS techniques.

2-Propanol↗
PubMed2000

Models for the active site of vanadium-dependent haloperoxidases: insight into the solution structure of peroxo vanadium compounds.

A combined use of electrospray ionization-mass spectrometry (ESI-MS), 51V NMR spectroscopy and ab initio calculations has been proved to be a powerful tool for obtaining direct information of the structure and the chemistry of peroxo vanadates in solutions. The analysis of acid solutions containing monoperoxo vanadates showed the occurrence of exchange reactions between solvent molecules in the coordination sphere of the metal. On the other hand, bisperoxo vanadates appear to be less prone to coordinate more than one water or alcohol molecule. The bisperoxo complex [VO5]- in the presence of histidine and histidine-like ligands, at near neutral conditions, has been studied. Coordination of one and two molecules of ligand is observed affording [VO5L]- and [VO5L2]-, respectively. Characterization of these species has been obtained by MSn experiments, which allowed us to distinguish specific fragmentations of the peroxidic moiety.

Binding Sites↗
PubMed2000

Albumin permeability in isolated glomeruli in incipient experimental diabetes mellitus.

AIMS/HYPOTHESIS: The pre-clinical phase of diabetic nephropathy is characterised by increased glomerular filtration rate and episodes of microalbuminuria. The cause of the microalbuminuria has been variably ascribed to alterations of the size or charge selective barriers of the glomerulus or both or as a consequence of the haemodynamic changes. Our aim was to investigate very early albumin permeability alterations in isolated glomeruli which were not subject to perfusion pressure. METHODS: Isolated glomeruli were studied from 120 male Wistar rats, divided into three groups: streptozotocin-treated, streptozotocin-treated with insulin pellet implants, and controls. From each group ten animals were killed at 7, 14, 28, and 56 days after induction. Study variables included blood pressure, proteinuria, iopamidol clearance, albumin permeability and glomerular area. Subsequently, albumin permeability, proteinuria, and iopamidol clearance were determined in an additional group of 40 diabetic animals studied at 24, 72, 96, and 120 h after induction. RESULTS: Albumin permeability increased steadily from induction in streptozotocin-treated animals, reaching a plateau at approximately 120 h. Glomerular filtration rate was shown to increase significantly at approximately 7 days and proteinuria correlated with it. Glomerular hypertrophy was observed both in streptozotocin-treated animals and in streptozotocin-treated rats with insulin pellet implants. Strict blood glucose control delayed the appearance of the permeability defect in isolated glomeruli and inhibited the increase in glomerular filtration in intact animals. It did not prevent glomerular hypertrophy. CONCLUSION/INTERPRETATION: An albumin permeability defect exists early in isolated non-perfused glomeruli from streptozotocin-treated rats and seems to be independent of glomerular filtration rate alterations.

Animals↗
PubMed1999

Prediction and treatment of recurrent focal segmental glomerulosclerosis after renal transplantation in children.

The recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation has a potentially detrimental course toward the loss of renal function. To identify prognostic markers for recurrence and efficacy of treatment, we evaluated the outcome of 32 renal allografts in 29 pediatric patients with FSGS who underwent transplantation from 1987 to 1998 in the North Italy Transplant program. Recurrence was observed in 15 of 29 patients (52%) after the first transplant and in 3 of 3 patients (100%) after the second graft. No significant differences in sex, age at FSGS onset, age at transplantation, or length of dialysis were noted between patients with recurrent and nonrecurrent FSGS. Those with recurrence originally developed end-stage renal failure faster (3.9 years) than those without recurrence (6.2 years). Pretransplantation serum samples from 25 patients were tested in an in vitro assay that evaluates glomerular permeability to albumin. FSGS recurred in 11 of 13 children who tested positive for the permeability factor and in 4 of 12 patients with a negative test result; the odds ratio for developing recurrence was 10.99 (95% confidence limit, 1.6 to 75.47) in the former group. The immediate onset of proteinuria after transplantation was a negative prognostic factor for the outcome; 6 of 9 patients in whom proteinuria appeared within 2 days of transplantation returned to dialysis in less than 24 months. In 9 of 11 patients who were treated with plasmapheresis plus cyclophosphamide after recurrence, proteinuria was successfully reversed and persistent remission was obtained in 7 patients. These data show that the glomerular permeability test has a significant predictive value for the recurrence of proteinuria in children with FSGS who have received a renal allograft. Of the clinical parameters considered, only the duration of disease was significantly different in patients with recurrent versus nonrecurrent FSGS. Treatment with plasmapheresis plus cyclophosphamide can be effective in the control of FSGS relapse after renal transplantation.

Albumins↗
PubMed1998

Effects of a dimeric vs a monomeric nonionic contrast medium on renal function in patients with mild to moderate renal insufficiency: a double-blind, randomized clinical trial.

The efficacy and safety of nonionic dimeric contrast media in subjects with impaired renal function is largely unknown. The present study was aimed at determining the risk of tubular nephrotoxicity in patients with mild to moderate renal insufficiency who underwent intravenous urography (IVU) with the nonionic dimeric contrast agent iodixanol (Visipaque, Nycomed Imaging, Oslo, Norway). In a double-blind protocol 64 patients (55 males; mean age 68.3 years) with serum creatinine between 135 and 265 micromol/l who were to undergo IVU were randomized to receive iodixanol (a nonionic dimer) or iopromide (a nonionic monomer), 600 mg I/kg b. w. Renal function was evaluated before and 1 h, 6 h, 24 h, 48 h and 7 days after IVU with analysis of serum creatinine, urinary enzymes alanylaminopeptidase and N-acetyl-beta-glucosaminidase, and urinary microproteins alpha-1-microglobulin and albumin. Renal function remained stable in both contrast medium groups during the follow-up period. No statistically significant differences were observed between the monomer and the dimer in terms of urinary enzyme and microprotein excretion or serum creatinine. Transient radiocontrast-induced nephropathy developed in 1 patient who had received iodixanol. The administration of the nonionic dimeric contrast medium iodixanol, or of the nonionic monomer iopromide, entailed a low nephrotoxic potential in patients with mild to moderate renal insufficiency undergoing excretory urography.

Acetylglucosaminidase↗
PubMed1998

Relationship between whole-body protein turnover and serum creatinine in chronically uremic patients.

To investigate the relationship between decline in renal function and alterations of protein metabolism we determined the rate of whole-body protein turnover in a group of 15 postabsorptive chronically uremic patients (9 males and 6 females) with different levels of serum creatinine concentrations (average 5.7 +/- 0.4 (SE) mg x dl(-1); range 3.3-9.1). Patients' age and body mass index were 53 +/- 4 years (range 26-73) and 24.7 +/- 0.6 kg/m2 (range 20.3-28.7), respectively. Nutritional status (plasma albumin 3.6 +/- 0.4 g x dl[-1]) and acid-base equilibrium (arterial pH 7.38 +/- 0.01) were fairly controlled by therapy. Whole-body leucine rate of appearance (Ra), an index of whole-body protein turnover, was assessed using a stable isotope technique. L-[1-(13)C]leucine was continuously infused and plasma [1-(13)C]alpha-ketoisocaproic acid enrichment was determined in steady-state conditions as a marker of the intracellular leucine enrichment. The average leucine Rawas 2.03 +/- 0.13 micromol x kg(-1) x min(-1) (range 1.29-3.19). Using simple linear regression analysis, the coefficient of correlation between the individual values of serum creatinine concentration and leucine Ra was 0.59 (n = 15; p = 0.02). Leucine Ra did not significantly correlate with blood pH or plasma albumin. In conclusion, we found a positive linear relationship between the values of plasma creatinine concentration and the rate of whole-body protein degradation. This correlation suggests that the progression of renal insufficiency is associated with accelerated rates of turnover of body proteins.

Adult↗
PubMed1998

Pulmonary hypertension associated with human immunodeficiency virus infection. Report of two cases and review of the literature.

Recent reports have suggested a possible association between HIV-1 infection and "idiopathic" pulmonary hypertension (PH), but the pathogenetic role of the viral agent has not been fully defined yet. We report the cases of two white males positive for human immunodeficiency virus type 1 (HIV-1) who presented with clinical and hemodynamic diagnosis of pulmonary hypertension. They were heterosexual, non-hemophiliac, heroin abusers with no signs of clinical AIDS. Neither one of the patients had opportunistic lung infections or any other cause of secondary pulmonary hypertension. In one case, peculiar clinical and electrocardiographic features of PH were associated with signs of thrombotic thrombocytopenic purpura (TTP). The association between PH and HIV-1 infection might be explained by a severe alteration of pulmonary endothelial cell homeostasis secondary to HIV-1 viral infection.

Adult↗
PubMed1997

Mechanisms of malnutrition in uremia.

The pathogenesis of protein wasting in chronic renal failure is multifactorial. Potential mediators of protein catabolism in chronic uremia include anorexia, low protein-energy intake, increased cortisol and parathyroid hormone secretion, insulin resistance, metabolic acidosis and unidentified uremic toxins. In non-acidotic uremic patients the rate of protein turnover (that is, synthesis and degradation) has often been found to be decreased. Malnutrition also decreases both protein synthesis and degradation. In contrast, during acidosis protein degradation is primarily accelerated and results in rapid loss of body proteins. Cytokine concentrations have often been found increased in both dialyzed and undialyzed chronically uremic patients. Our study determined the circulating levels of TNF-alpha and of type I (60 kDa) and type II (80 kDa) soluble TNF-alpha receptors in undialyzed uremic patients, and found that their plasma levels were greatly increased. Serum creatinine correlated with TNF-alpha soluble receptors but not with the TNF-alpha. Thus, TNF-alpha is potentially an important mediator of protein wasting in chronically uremic patients. Pharmacological therapy of protein catabolism in chronic uremia may include the administration of pentoxifylline, which has been shown to decrease protein degradation by interfering with the TNF-alpha system (that is, TNF-alpha and its soluble receptors) in experimental models. Growth hormone and insulin-like growth factor-1 administration may also be beneficial in these patients, but further evaluation of the hormone effects on glucose and glutamine metabolism is called for.

Adult↗
PubMed1997

[A comparison between an ionic paramagnetic contrast agent (Gd-DTPA) and a nonionic one (Gd-DTPA-BMA) in functional kidney evaluation with magnetic resonance].

INTRODUCTION: The combination of TGE sequences with bolus injection of paramagnetic contrast agents permits to study renal function and perfusion. We studied renal function with both an ionic (Gd-DTPA) and a nonionic paramagnetic contrast agent (Gd-DTPA-BMA) to compare their kinetics in normal kidneys. MATERIAL AND METHODS: Twenty MR examinations were performed on 20 subjects with normal renal function. Ten subjects were examined after i.v. injection of Gd-DTPA and the other ten subjects after i.v. injection of Gd-DTPA-BMA. MR examinations were performed on a Philips ACS II unit (1.5 T). Two sequences were acquired in all cases; an SE coronal T1-weighted sequence (TR/TE = 600/19 ms) and a TGE coronal T1-weighted sequence (TR/TE = 12/5 ms, flip angle = 25 degrees) performed after bolus injection of the contrast agent at 0.1 mmol/kg. Signal intensity time curves were obtained in all the cases. The signal intensity of the cortex, corticomedullary junction, medulla and the pyelocaliceal system of each kidney was measured using a region of interest (ROI). Signal intensity curves were analyzed considering some quantitative parameters such as the area under the curve (AUC), the peak (P) and the time to peak (T-P). RESULTS: In the subjects with normal renal function, four phases were demonstrated after the i.v. injection of either Gd-DTPA or Gd-DTPA-BMA, namely the cortical phase, the cortico-medullary junction phase, the medullary phase and the pyelocaliceal system phase. No statistically significant differences between the two agents were demonstrated in signal intensity time curves and quantitative parameters. CONCLUSIONS: Gd-DTPA and Gd-DTPA-BMA showed the same efficacy in renal function studies.

Analysis of Variance↗
PubMed1996

Dose effect of nitrendipine on urinary enzymes and microproteins following non-ionic radiocontrast administration.

BACKGROUND: Although calcium-channel antagonists have been proposed as prophylaxis to prevent radiocontrast-induced nephropathy, the dose and dose interval to achieve a protective effect have not been quantified in humans. METHODS: In a randomized, double-blind protocol we studied urinary enzyme and microprotein excretion in 121 outpatients (mean age 65.3 +/- 9.3 years, 62% male) with normal renal function who were to undergo digital subtraction arteriography with iohexol or iopentol. The subjects were treated with a single dose of placebo (group 1) or nitrendipine 10 mg (group 2) or 20 mg (group 3) p.o. 1 h before the procedure. Blood and urine samples were collected 1 h before, 1 h after, and 24 h after contrast administration. Study variables included contrast volume and serum creatinine, and urinary creatinine, osmolality, albumin, alanylamino-peptidase (AAP, a brush border enzyme), N-acetyl-beta-glucosaminidase (NAG, a lysosomal enzyme), and alpha-1-microglobulin (alpha-1-micro, a filtered microprotein). RESULTS: Serum values of creatinine remained unchanged during the study period. Albuminuria was not affected by contrast administration, whereas AAP, NAG, and alpha-1-micro increased significantly, all except AAP returning to baseline at 24 h. Pretreatment with nitrendipine did not reduce enzyme excretion, although AAP levels were lower in general in the group assigned to the 20-mg dose. Acute renal failure, defined as a 50% increase of serum creatinine 24 h after radiocontrast administration, was found in eight patients: four from group 1 (8.3%), three from group 2 (6.5%), and one from group 3 (3.7%). CONCLUSIONS: Neither the course of enzyme excretion nor the incidence of acute renal failure following radiocontrast administration were affected by single doses of calcium antagonists. AAP levels were lower in general in subjects taking the 20-mg dose of nitrendipine. This study also indicates that a single low or normal dose of nitrendipine per os is not effective prophylaxis before radiocontrast administration. The designs of future studies investigating the "nephroprotective' effect of calcium-channel antagonists per os should incorporate (1) the use of repeated doses to saturate hepatic metabolic pathways, and (2) the control of confounding variables in the measurement of urinary enzymes.

Acetylglucosaminidase↗
PubMed1995

[An atypical presentation of a case of Horton's giant-cell arteritis].

Horton giant cell arteritis can present with an atypical clinical picture that often resembles other diseases. In the case described below, the patient initially demonstrated clinical and laboratory evidence of a Candida albicans sepsis, and therefore we started antimycotic treatment with amphotericin B. Because of an adverse reaction to that drug, we added parenteral steroids before every administration of the antimycotic which led to an unexpected improvement of symptoms. This result caused us to reconsider some clinical aspects that could have been interpreted also as vasculitis, in particular for a giant cell arteritis: throbbing temporal headache, diffuse weakness, important rise in ESR, myoarthralgias. We performed a biopsy of the temporal artery that confirmed our diagnosis.

Amphotericin B↗