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F Scolari

Publications and source records attributed to F Scolari.

At least 37 records · Page 2Linked to original sources
PubMed1999

Familial clustering of IgA nephropathy: further evidence in an Italian population.

Several lines of evidence suggest that genetic factors have an important role in the pathogenesis of immunoglobulin A (IgA) nephropathy. We report the prevalence of familial IgA nephropathy in a referral center in northern Italy and present the data on HLA genotypes in the families identified. Twenty-six of 185 patients (14%) with IgA nephropathy investigated in Brescia, Italy, were related to at least one other patient with the disease. Restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta and HLA-DQ alpha and beta genes, as well as polymerase chain reaction-based oligonucleotide typing, was performed in family members. The 26 patients with IgA nephropathy belonged to 10 families. Familial relationships between the patients varied greatly, ranging from parent-child to sib-pair to more distant familial relationships. No common nephrotoxic factor was identified in the families. The intervals separating the apparent onset of disease in relatives with IgA nephropathy varied from 8 months to 13 years. In patients with a family history of IgA nephropathy, there was an increased incidence of HLA-DRB1*08 compared with those with sporadic IgA nephropathy. The study shows that a significant number of the patients with IgA nephropathy followed up in Brescia had a family history of disease. The fact that the Italian population, an ethnic group not previously examined, also presents an increased familial susceptibility to IgA nephropathy suggests that familial predisposition is a very common finding for IgA nephropathy. Thus, clinicians should become aware that IgA nephropathy may aggregate within families in a substantial number of cases. In addition, this subgroup of patients with IgA nephropathy offers an ideal opportunity to elucidate the molecular genetics of this disease.

Adolescent↗
PubMed1999

Identification of a new locus for medullary cystic disease, on chromosome 16p12.

Autosomal dominant medullary cystic disease (ADMCKD) is an interstitial nephropathy that has morphologic and clinical features similar to autosomal recessive nephronophthisis. The typical renal dysfunction associated with ADMCKD results mainly from a defect in urinary concentration ability, although results of urinalysis are normal. Recently, a locus on chromosome 1 was associated with ADMCKD, in DNA from two large Cypriot families, and genetic heterogeneity was inferred. We describe the genomewide linkage mapping of a new locus for medullary cystic disease, ADMCKD2, on chromosome 16p12 in a four-generation Italian pedigree. The family with ADMCKD2 fulfills the typical diagnostic criteria of ADMCKD, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 shows a maximum two-point LOD score of 3.68, and the defined critical region spans 10.5 cM, between D16S500 and SCNN1B1-2. Candidate genes included in the critical region are discussed.

Chromosome Mapping↗
PubMed1998

Are HLA class II and immunoglobulin constant region genes involved in the pathogenesis of mixed cryoglobulinemia type II after hepatitis C virus infection?

BACKGROUND/AIMS: Hepatitis C virus infection is known to play an important role in the pathogenesis of essential mixed cryoglobulinemia type II. Progression of hepatitis C virus infection to mixed cryoglobulinemia may be influenced by host immune response. To analyze the immunogenetic background of mixed cryoglobulinemia, we studied HLA-DR, DQ loci and the switch regions of immunoglobulin heavy chain gamma1 and gamma4 constant genes. METHODS: HLA typing was performed in 84 hepatitis C virus-infected patients (46 with cryoglobulins and 38 without), and 109 healthy controls, through analysis of restriction fragment length polymorphisms, supplemented with other techniques. Immunoglobulin heavy chain gamma1 and gamma4 polymorphisms, detected by restriction fragment length polymorphisms, were studied in 41 patients with mixed cryoglobulinemia and 51 controls. RESULTS: The gene frequency of DRB1*11 was significantly higher in patients with mixed cryoglobulinemia than in controls (0.36 and 0.20, respectively; p= 0.0035). However, DRB1*11 was also increased in the subgroup of patients without mixed cryoglobulinemia who did not develop severe liver disease, while it was decreased in those with severe liver damage (0.50 and 0.13; p=0.0035). The frequency of 5.4 kb allele of the immunoglobulin heavy chain gamma1 switch region was higher in patients with mixed cryoglobulinemia than in controls (0.47 and 0.22; pc=0.002), while the frequency of 5.5 kb allele was lower (0.51 and 0.78; pc= 0.001). CONCLUSIONS: Susceptibility to develop cryoglobulins after hepatitis C virus infection was not associated with HLA-DR or DQ. HLA-DRB1*11-positive individuals were protected from serious chronic liver disease after hepatitis C virus infection. Immunoglobulin heavy chain constant gamma1 switch region restriction fragment length polymorphisms were associated with mixed cryoglobulinemia.

Adult↗
PubMed1998

Autosomal dominant medullary cystic disease: a disorder with variable clinical pictures and exclusion of linkage with the NPH1 locus.

BACKGROUND: The nephronophthisis-medullary cystic disease (NPH/MCD) complex represents a heterogeneous group of hereditary tubulointerstitial nephritis. The most common variant is juvenile recessive NPH, for which a gene locus (NPH1) has been mapped on chromosome 2q13. MCD is a less common dominant condition usually recognized later in life, which resembles NPH in many aspects, still presenting remarkable clinical differences. Nothing is known about the chromosome locus of MCD. METHODS: Five MCD families were studied. Diagnosis was made by inference from family history, type of inheritance, clinical signs and histology. Multipoint linkage analysis was performed by markers D2S293, D2S340 and D2S160 spanning the entire NPH1 locus. RESULTS: Diagnosis of MCD was made in 28 affected members (16 males; 12 females), belonging to five families. Histological diagnosis was available in 10 patients; clinical diagnosis in 11; seven deceased relatives had diagnosis of chronic nephritis. The age at diagnosis ranged from 8 to 65 years. Renal medullary cysts were found in a minority of patients. In family 1, the disease was associated with hyperuricaemia and gouty arthritis. Progression of renal disease presented intra- and extra-family variability with members of the same family showing mild elevation of creatinine or terminal renal failure. The NPH1 locus associated to recessive NPH was excluded from linkage to the dominant MCD. CONCLUSIONS: MCD might be more common than previously assumed. Variability in clinical presentation and absence of histopathological hallmarks contribute to make the diagnosis uncommon. The most remarkable clinical difference with NPH is the age of onset in some kindreds and a delayed progression towards renal failure. The exclusion of linkage to the NPH1 locus suggests the existence of an MCD responsible locus, still to be mapped.

Adolescent↗
PubMed1998

Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study.

BACKGROUND: Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. STUDY DESIGN: In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. RESULTS: Serum bicarbonate levels and arterial pH increased respectively from 19.3 +/- 0.6 mmol/l to 24.4 +/- 1.2 mmol/l (P < 0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (P < 0.0001). Serum albumin increased from 34.9 +/- 2.1 g/l to 37.9 +/- 2.9 g/l (P < 0.01), while PCRn decreased from 1.11 +/- 0.17 g/kg/day to 1.03 +/- 0.17 g/kg/day (P < 0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. CONCLUSIONS: Our data demonstrate that correction of metabolic acidosis improves serum albumin concentrations in HD patients. The correction of acidosis induces a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.

Acidosis↗
PubMed1998

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

Adolescent↗
PubMed1997

Immunogenetics of Henoch-Schoenlein disease.

In order to investigate the genetic basis of susceptibility to Henoch-Schoenlein purpura (HS), blood samples of 152 patients, 105 of whom had renal disease, were collected in a two-step study. The evaluation of DRB, DQB and DQA polymorphism was done by analysis of the restriction polymorphisms produced by TaqI enzyme. DRB1*07 was less frequent in patients than in the control group (gene frequency 0.09 and 0.18, respectively; P = 0.0023), whereas 64% of the patients were positive for DRB1*01 and/or DRB1*11 compared with 48% of the control group (P = 0.0069). Polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) typing of DRB1*01- and DRB1*11-positive individuals did not show any deviation of frequencies of DRB1*01 subtypes between patients and controls, whereas among DRB1*11 subtypes DRB1*1104 was significantly increased in the patients (Pc = 0.033). The comparison between patients with renal disease and those without renal disease showed no significant differences in the frequency of the single DRB, DQB and DQA alleles. The study of restriction polymorphisms in the switch region of the constant genes alpha 1, alpha 2 and mu of the heavy chains of immunoglobulins, using the enzyme Sacl and a specific probe, did not show any difference between 44 patients and 54 controls. This study demonstrates that susceptibility to HS also has a genetic origin: on one hand, the presence of DRB1*01 or DRB1*11 makes disease onset easier; on the other hand, DRB1*07 could induce some resistance to the disease. It is suggested that, as well as for other diseases caused by an impaired immune response, single amino acids in a key position in the HLA-DRB molecule make it more or less easy to recognize some antigenic peptide, towards which an immune response leading to disease is triggered.

Adolescent↗
PubMed1997

A large TSC2 and PKD1 gene deletion is associated with renal and extrarenal signs of autosomal dominant polycystic kidney disease.

BACKGROUND: The renal lesions in tuberous sclerosis complex (TSC) consist in multiple angiomyolipomas, often associated with cysts of variable size. Recently a few TSC patients with early-onset renal cysts resembling the autosomal dominant polycystic kidney disease (ADPKD) have been described. Virtually all of them showed deletions of both TSC2 and PKD1 genes. METHODS: Two unrelated families in which TSC and PKD co-segregate were investigate. 16p13.3-linked haplotype segregation, Southern blot, pulsed field gel electrophoresis, and loss of heterozygosity analyses were performed in both affected and unaffected family members. RESULTS: The proband from family 1 was first recognized as presenting typical neurological signs and skin lesions of TSC and multiple renal cysts at 12 years of age. Haemodialysis became necessary at age 28. CT and MRI scans revealed multiple cysts in the live and an asymptomatic, 3-4 mm aneurysm of the middle cerebral artery. His mother, who died at 47 of breast cancer, had ADPKD and reached the ESRD at 42. She showed facial angiofibromas. Both patients carried a submicroscopic germline deletion spanning the entire TSC2 gene and the large majority of PKD1 coding sequence. In the proband from family 2, the TSC diagnosis was made at 4 years. Enlarged polycystic kidneys causing and-stage renal failure at 19 years were observed. This patient carried a large germline, de novo deletion involving the entire TSC2 and PKD1 genes. In addition we could show in a renal hamartoma from this subject the loss of heterozygosity of markers spanning the TSC2 and PKD1 genes from the residual, normal chromosome 16 of paternal origin. CONCLUSIONS: The presence of a deletion involving both TSC2 and PKD1 genes should be considered in the clinical assessment of TSC children with an early-onset polycystic kidney disease, and more generally in all ADPKD patients who develop end-stage renal failure prior to the fourth or fifth decade of life. Finally, the occurrence of typical renal and extrarenal signs of ADPKD in a PKD1 hemizygote individual seems to support concept that a somatic inactivation of the residual PKD1 gene is required for the development of the cysts.

Adult↗
PubMed1996

X-linked Alport syndrome: an SSCP-based mutation survey over all 51 exons of the COL4A5 gene.

The COL4A5 gene encodes the alpha5 (type IV) collagen chain and is defective in X-linked Alport syndrome (AS). Here, we report the first systematic analysis of all 51 exons of COL4A5 gene in a series of 201 Italian AS patients. We have previously reported nine major rearrangements, as well as 18 small mutations identified in the same patient series by SSCP analysis of several exons. After systematic analysis of all 51 exons of COL4A5, we have now identified 30 different mutations: 10 glycine substitutions in the triple helical domain of the protein, 9 frameshift mutations, 4 in-frame deletions, 1 start codon, 1 nonsense, and 5 splice-site mutations. These mutations were either unique or found in two unrelated families, thus excluding the presence of a common mutation in the coding part of the gene. Overall, mutations were detected in only 45% of individuals with a certain or likely diagnosis of X-linked AS. This finding suggests that mutations in noncoding segments of COL4A5 account for a high number of X-linked AS cases. An alternative hypothesis is the presence of locus heterogeneity, even within the X-linked form of the disease. A genotype/phenotype comparison enabled us to better substantiate a significant correlation between the degree of predicted disruption of the alpha5 chain and the severity of phenotype in affected male individuals. Our study has significant implications in the diagnosis and follow-up of AS patients.

Adult↗
PubMed1996

Cholesterol atheromatous embolism: an increasingly recognized cause of acute renal failure.

BACKGROUND: Cholesterol atheromatous embolism is a systemic disease resulting from cholesterol crystal embolization to many organs, including the kidney. Vascular surgery, vascular radiology investigations and anticoagulation have been identified as inciting factors. METHODS: Fifteen patients with extensive atherosclerosis, presenting with simultaneous occurrence of acute renal failure and peripheral ischaemic changes were diagnosed as having acute renal failure due to cholesterol atheromatous embolism. RESULTS: The patients, 12 men and three women, had an average age of 65 years. In one patient, spontaneous occurrence of the disease was observed. An inciting factor was identified in 14 patients: aortography in 10, aortic surgery in two, and thrombolysis in two. Clinical course of acute renal failure was quite variable. Four patients required dialysis; 11 were conservatively managed. All patients had concomitant skin lesions, including digital mottling, cyanosis and gangrene of the toes, and livedo reticularis of the lower limb and abdomen. Eosinophilia was the most common laboratory abnormality. The diagnosis of cholesterol atheromatous embolism was confirmed by tissue examination in eight; in three it was based on the finding of retinal cholesterol emboli; in four patients it was made on clinical grounds. Seven patients died within 36 months. Death was most commonly from cardiac causes. CONCLUSIONS: Since the population at risk for cholesterol embolism is growing and the disease is iatrogenic in origin, we should expect to detect cholesterol embolism with greater frequency as cause of acute renal failure in the future.

Acute Kidney Injury↗
PubMed1995

Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome.

Mutations in the COL4A5 gene, which encodes the a5 chain of type IV collagen, are found in a large fraction of patients with X-linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5' ends of both COL4A5 and COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end-stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome.

Adolescent↗