Search PubMed⌕ Search

Biomedical subjects

R Coppo

Publications and source records attributed to R Coppo.

At least 19 recordsLinked to original sources
PubMed2001

[Neonatal chronic kidney failure associated with cyclo-oxygenase-2 inhibitors administered during pregnancy].

Non-steroidal anti-inflammatory drugs (NSAID) are used since years as tocolytic due to their capacity to inhibit cyclo-oxygenase (COX) expressed in uterus and fetal membranes, fundamental for labour initiation and maintenance. The use of nimesulide, a COX-2 selective NSAID, has been recently proposed due to its capacity to selectively inhibit the enzyme expressed in the myometrium and endometrium. A case of neonatal irreversible end stage renal failure after maternal assumption of nimesulide as tocolytic for 6 week is reported. Cesarean section at the 32nd week due to oligohydramnios gave birth to a baby girl of 2090 g, in good general conditions, without signs of respiratory distress and of visible abnormalities. From birth she displayed oligo-anuria which required dialytic substitutive therapy from the second day of life. At US scan both kidneys had normal diameters for gestational age slightly increased echogenicity and a reduced cortico-medullary differentiation. On the 20th day of life she had a surgical renal biopsy for the persistence of oligo-anuria, showing fetal glomeruli, without lymphocytic interstitial infiltrate, and normal tubuli without evidence of necrosis. She is now 16 months old and under automated peritoneal dialysis on a home dialysis program. The occurrence of chronic renal failure in strict relationship with maternal nimesulide assumption in this case is strongly suggestive for a pharmacological damage, either direct or mediated by renin angiotensin inhibition, and possibly modulated by genetic factors, likely to account for the different outcome of similarly treated patients. A cautious use of this drug as long term tocolytic should be recommended while waiting for ad hoc experimental and clinical evidences of safeness.

Adult↗
PubMed2000

The emergency management of severe hypertension.

Severe hypertension in childhood is a life-threatening clinical problem that carries with it not only serious sequelae of inadequate treatment but equally serious complications of over enthusiastic therapy. The majority of cases have some form of underlying renal disease. Therapeutic success is achieved by slow and safe reduction of blood pressure with the immediate target of avoiding hypertensive sequelae yet allowing preservation of target organ function. Short-acting parenteral antihypertensives are recommended along with careful blood pressure monitoring to prevent complications arising through loss of autoregulatory control.

Antihypertensive Agents↗
PubMed2000

Bradykinin and nitric oxide generation by dialysis membranes can be blunted by alkaline rinsing solutions.

BACKGROUND: Bradykinin (BK) generation following the first contact of blood with the dialysis materials is thought to enhance hypersensitivity reactions (HSRs). Some of the effects of BK are mediated by nitric oxide (NO). We have recently reported that the pH of diluted blood modulates the kinin system. The present study was aimed to investigate the role of the pH of culture media and filter-washing solutions and BK and NO generation, either in vitro and ex vivo. METHODS: BK was measured by a specific enzyme-linked immunosorbent assay (ELISA), and NO synthase (NOS) activity by 3H-citrulline production after incubation with 3H-arginine and nitrites by using the Griess reagent. In in vitro experiments, NOS activity was detected in endothelial cells (ECs) cultured with graded BK concentrations at various pH values. Blood from 30 patients in regular dialysis was ex vivo circulated in one single passage through minifilters prerinsed with pH 7 or pH 8 phosphate buffer (PB) solutions. The out-flowing blood was tested for BK and nitrite content and was incubated with cultured ECs to evaluate its capacity to modulate NOS activity. RESULTS: BK induced in vitro a dose-dependent increase in NOS activity of ECs, which was mediated by tyrosine kinase phosphorylation. NO generation was enhanced at pH 7.2, which remained unchanged at pH 7.6. In ex vivo experiments, blood out-flowing after one passage on filters washed with pH 7 PB solutions had increased BK levels (P < 0.0001), increased nitrites (P < 0.05), and enhanced EC NOS activity (P < 0. 05) in comparison to data found when filters were washed with pH 8 PB. Only when the filters were rinsed with a solution at pH 7 did PAN DX and AN69 membranes show a distinct BK generation capability, and cuprophane a peculiar capability to enhance NOS. Such effects were prevented when dialyzers were prerinsed with pH 8 PB. Multiple regression analysis showed that the pH of the uremic blood was the driving factor for BK and NOS activation (r = 0.54, P < 0.02). CONCLUSIONS: BK and NO generation are modulated by environmental pH. Rinsing the blood and dialysate compartments of filters with an alkaline solution prior to use may mitigate the activation of mediators likely to be involved in some HSRs.

Acidosis↗
PubMed2000

Integrin expression and IgA nephropathy: in vitro modulation by IgA with altered glycosylation and macromolecular IgA.

BACKGROUND: Signal transduction by mesangial cell (MC) integrins regulates cell growth and survival, extracellular matrix production, and organization. The aim of the study was to investigate human MC integrin modulation by differently glycosylated IgA and macromolecular IgA, which are thought to play a pathogenetic role in IgA nephropathy (IgAN). METHODS: MCs were incubated with purified human polymeric IgA, heat-aggregated IgA, IgA glycoforms generated by enzymatic hydrolysis of saccharide residues and serum fractions from IgAN patients, and controls isolated by lectin affinity and containing IgA with peculiar glycan patterns. Integrins were quantitated by flow cytometry. RESULTS: Cultured MCs highly expressed alphavbeta3 and some alpha3beta1; alphavbeta3 was up-regulated by matrix components (P < 0.02). In vitro desialylated and degalactosylated polymeric human IgA enhanced alphavbeta3 expression on cultured MCs (P < 0.001). Serum IgA glycoforms isolated from IgAN patients with high exposure of internal sugars, GalNAc, Neu5Ac2,6GalNAc, and Man enhanced alphav expression on cultured MCs more than healthy controls. CONCLUSIONS.: These data support the hypothesis that IgA glycation plays a role in modulating the cell-matrix interaction, and that this mechanism can be operating in IgAN.

Antibodies, Monoclonal↗
PubMed2000

Nitric oxide mediates cyclosporine-induced apoptosis in cultured renal cells.

BACKGROUND: The clinical use of cyclosporine (CsA) is limited by its nephrotoxicity. Apoptosis, perhaps instigated by increased nitric oxide synthase (NOS) activity, may play a role in such toxicity. METHODS: Human mesangial cells, human tubular cells, human umbilical vein endothelial cells, or murine endothelial cells were cultured with CsA at final concentrations of 0 to 1000 ng/mL for 4 to 24 hours. As inhibitors of apoptosis, 0.01 mol/L L-nitromethylarginine (L-NAME) or 1 microg/mL cycloheximide (CHX) was added, whereas 0.01 mol/L sodium nitroprusside (as a nitric oxide donor) was used as a positive control. Apoptosis was assessed by using TUNEL method and by DNA fragmentation by electrophoresis. In addition, NOS enzymatic activity, Northern blots for inducible NOS (iNOS) mRNA, and immunohistochemically demonstrable iNOS protein were evaluated. RESULTS: Within 12 to 24 hours, CsA significantly increased the fraction (8 to 35%) of apoptotic cells in each cell line, according to the dose. Fragmentation of DNA confirmed apoptosis. L-NAME and CHX inhibited the phenomenon, whereas sodium nitroprusside enhanced it. Each cell line significantly increased NOS activity in response to CsA, an effect blunted by L-NAME and CHX. Neither inhibitor modified the increased iNOS mRNA expression elicited by CsA. Positive staining for both iNOS and p53 proteins was observed in all cell lines incubated with CsA that were inhibited by CHX; L-NAME inhibited only p53 staining. CONCLUSIONS: CsA induces apoptosis in various renal cell lines, and this effect is mediated by the induction of iNOS via p53. These effects may contribute to the acellular fibrosis characteristic of late CsA nephrotoxicity.

Apoptosis↗
PubMed2000

Aberrantly glycosylated IgA molecules downregulate the synthesis and secretion of vascular endothelial growth factor in human mesangial cells.

To gain insight into the glomerular capillary repair mechanisms in immunoglobulin A (IgA) nephropathy, we focused on vascular endothelial growth factor (VEGF-A) and nitric oxide (NO). Because abnormal glycosylation of serum IgA has been shown in IgA nephropathy, we examined whether VEGF-A and NO production by mesangial cells (MCs) could be modulated by aberrantly glycosylated (desialylated or degalactosylated) IgA. VEGF-A and NO synthase (NOS) gene expression were examined by reverse-transcriptase polymerase chain reaction (RT-PCR) or Northern blot analysis, and VEGF-A peptide, by capture enzyme-linked immunosorbent assay and NOS activity as production of tritium ([(3)H]) citrulline from [(3)H] arginine. Semiquantitative densitometric analysis of RT-PCR experiments showed a significant downregulation of VEGF-A messenger RNA (mRNA) in MCs incubated with aberrantly glycosylated IgA. This resulted in decreased release of VEGF-A in culture medium (P: < 0. 01). NOS activity and inducible NOS (iNOS) mRNA were enhanced by aberrantly glycosylated IgA (both P: < 0.01). No modulation of constitutive NOS mRNA was found. The depression of the VEGF-A production induced by aberrantly glycosylated IgA was mediated by NO because it was completely reversed by the NOS inhibitor, N:omega-nitro-L-arginine methyl ester. The NO donor, sodium nitroprusside, induced a bimodal modulation of VEGF; although low concentrations (0.0001 nmol/L) increased VEGF-A synthesis, greater concentrations (1,000 nmol/L) depressed it. In conclusion, we report negative control of VEGF-A synthesis in MCs by aberrantly glycosylated IgA, mediated by enhanced iNOS activity. We speculate that both increased iNOS activity and depressed VEGF-A synthesis might have a role in impairing vascular repair and favor sclerosis in IgA nephropathy.

Down-Regulation↗
PubMed2000

[Treatment of fluid overload and kidney failure with periotoneal dialysis after heart surgery].

BACKGROUND: Infants undergoing cardiac surgery with prolonged cardio-pulmonary bypass are particularly exposed to the risk of acute renal failure for renal hypoxia due to low cardiac output. METHODS: To limit fluid overload deriving from oligo-anuria and low cardiac output we have recently adopted an early peritoneal dialysis protocol, positioning the peritoneal catheter during the intervention and performing early exchanges at first signs of inadequate diuretic response and/or "leaky capillary syndrome" with diffuse edema. From 1-1 to 31-12-1997 12 patients (8 males), of median age of 65.5 days (range 1-350 days) and median weight of 3463 g (range 2380-6550 g) were treated with peritoneal dialysis (automated exchanges of 10 ml/kg body weight of 1.5% glucose, dwell time 20 minutes). Cardiac pathologies included complex hearth malformations. Cardiopulmonary bypass lasted a mean of 202 minutes (range 102-372 minutes). The children were treated for a minimum of 1 to 42 peritoneal dialysis sessions. The infusional therapy included human albumin and fresh frozen plasma to substitute losses and furosemide at the dose of 4 mg/kg/day to reduce the "leaky capillary syndrome". RESULTS: The results were very satisfactory: only 3 children died in the first 30 days after surgery. Renal function was normal at the end of the observation in 8/12 cases, and 2 cases presented chronic renal failure. CONCLUSIONS: Since similar series report a mortality rate of 33-79%, it is suggested that early peritoneal dialysis may have positively influenced the final survival rate.

Cardiopulmonary Bypass↗
PubMed1999

Clinical features of Henoch-Schönlein purpura. Italian Group of Renal Immunopathology.

Henoch-Schönlein purpura (HSP) is a vasculitis that often involves the kidneys with a IgA nephropathy indistinguishable from Berger's disease. It can affect patients of any age, even though an uneven distribution of prevalence and severity of renal disease is commonly observed as the renal involvement with transient hematuria without renal functional impairment is much more frequent in children than in adults. The Italian Group of Renal Immunopathology analyzed a cohort of HSP patients with the homogeneous criterium of a renal disease severe enough to indicate renal biopsy both in adults and in children. We report the clinical features of 219 HSP patients (136 adults and 83 children) enrolled from 43 Italian Centers of Nephrology. The diagnosis was based on the detection of IgA nephropathy in a clinical setting of palpable purpura and/or bowel angina. The peak age was in second decade (28% of the patients). In 37% of the cases a potential eliciting factor was identified, mostly infectious (41% in children vs 23% in adults, p < 0.05). A seasoned incidence was found in June (20% of the cases). Most patients had palpable purpura (96.3%), while bowel angina was reported in 54.1% and arthritis in 50.2% at onset. The full extrarenal syndrome was more frequent in children (59%) than in adults (47%, p < 0.05). The extrarenal signs were often not coincident with urinary manifestations. The clinical onset with nephrotic syndrome was more common in children than in adults (35% vs 24.3% respectively, p < 0.02) who more often presented with minimal or moderate proteinuria. The frequency of impaired renal function at onset was similar in both adults and children (24.2% and 31.2% respectively).

Adolescent↗
PubMed1998

Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schoenlein patients. Italian Group of Renal Immunopathology.

BACKGROUND: The influence of angiotensin converting enzyme (ACE) gene polymorphism on the progression of primary IgA nephropathy (pIgAN) is still debated. Even though the allele frequency was reported to be similar to controls, in some studies D/D patients had a faster decline of renal function and need of dialysis. Since Henoch-Schoenlein purpura (HSP) nephritis is considered a systemic vasculitis with renal lesions indistinguishable from pIgAN, we investigated the effect of the ACE polymorphism on presentation and progression of HSP IgAN. METHODS: We examined the insertion (I) and deletion (D) polymorphism in intron 16 of ACE gene by PCR amplification of genomic DNA of 82 patients (37 children), with biopsy-proven IgAN associated with HSP enrolled in a collaborative study. RESULTS: No significant association with clinical presentation at onset or with final outcome was found (functional impairment at outcome in 31.8%, D/D, 27.4%, I/D and 44% I/I, heavy proteinuria in 36.3% D/D, 21.6% I/D, and 11.1% I/I). Patients homozygous for the D allele had a greater number of extrarenal relapses (P=0.0028). No association was found between the ACE genotype and the presence of hypertension at onset and at the end of the follow-up. No difference was found between adults and children. CONCLUSIONS: In this cohort of HSP IgAN, no ACE I/D polymorphisms were found to be associated with progressive deterioration of renal function. Different genes possibly involved in vasculitis might more strictly modulate expression and evolution of HSP IgAN.

Adolescent↗
PubMed1998

Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian National Registry of Renal Biopsies in Children). Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal Immunopathology of the Italian Society of Nephrology.

BACKGROUND: Children's renal biopsy data were gathered for 3 consecutive years (1992-1994) by the Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology, which opened a paediatric section of the Italian Registry of Renal Biopsies. MATERIALS: The Registry recorded the histological diagnosis and the clinical data at renal biopsy of 432 children < or = 15 years old (mean age 8.96 +/- 3.7 years). RESULTS: The most common glomerulonephritis (GN) at renal biopsy was idiopathic IgAGN (18.8%) and the most frequent secondary GN was Henoch-Schönlein purpura (HSP) nephritis (11.6%). Minimal-change disease (MCD) accounted for 11.6%, focal and segmental sclerosis (FSG) 8.5%, mesangial proliferative GN (MPGN) 9.5%, membranoproliferative GN 5.5%, and thin-membrane disease 5%. Lupus nephritis was diagnosed in 5% and Alport's GN in 3.9% of the cases. The annual incidence of primary GN in Italian children was 11.1 cases per million children population (p.m.c.p.), IgAN accounting for 3.1 cases, MCD 2.3, and HSP nephritis 1.9 cases p.m.c.p. respectively. Italian children underwent renal biopsy because of isolated microscopic haematuria in 19.3% of the cases, non-nephrotic proteinuria with or without microscopic haematuria in 31.2%, and nephrotic-range proteinuria in 34.2%, less frequently (15.3%) because of acute or chronic renal failure. Children with persistent isolated microscopic haematuria had most frequently IgAN (34.9%) or thin-membrane disease (25.3%), while those with non-nephrotic proteinuria had IgAN (30.4%) and HSP nephritis (23%). In cases with nephrotic proteinuria renal biopsy showed MCD in 34.5% of the cases, FSG in 16.9%, and MPGN in 12.2%. When renal biopsy was performed in chronic renal failure, chronic interstitial renal disease was detected in 62.5% of the cases. CONCLUSIONS: This National Registry provides data on the indications for performing renal biopsy in Italian children and on the frequency and annual incidence of histological lesions detected. IgAN, primary or related to HSP, was the most common nephritis in Italian children undergoing renal biopsy.

Adolescent↗