Familial IgA nephropathy.

To date, more than 90 families with multiple members with IgA nephropathy have been reported. The case for genetic predisposition as a cause of familial clustering of IgA nephropathy is supported by several factors, including variable time points in the onset of the disease in relatives with IgA nephropathy; the presence of abnormalities of IgA production in both affected and unaffected family members; the clustering of the birthplaces of ancestors of large pedigrees containing multiple affected members with IgA nephropathy, which suggests the existence of a "founder effect". Immunogenetic studies does not conclusively indicate that HLA is involved in the pathogenesis of IgA nephropathy. The specific mode of inheritance of familial IgA nephropathy is difficult to establish with certainty. IgA nephropathy may be a single gene trait with incomplete penetrance. Alternatively, a multifactorial genetic disease could account for the increased prevalence of the disorder among relatives of affected individuals. Clinicians must become aware that IgA nephropathy may aggregate within families in a substantial number of cases. The availability of multiplex families offers an ideal opportunity to design a molecular genetics approach to map the gene(s) or pathway(s) responsible for the development of IgA nephropathy.     

Screening for tuberculosis and latent tuberculosis infection among undocumented immigrants at an unspecialised health service unit.

SETTING: Practical or cost-effective strategies to identify undocumented immigrants with latent tuberculosis infection and to deliver treatment for latent TB infection are still unavailable. OBJECTIVES: To compare completion rates of screening procedures for TB infection and disease among undocumented immigrants at specialised (TB) and unspecialised health services in Italy. DESIGN: A TB unit (TBU) and an unspecialised health service unit for migrants (MHCU) served as recruitment sites for recent undocumented immigrants from TB endemic areas. The screening included a symptom questionnaire, a tuberculin skin test and a chest X-ray. RESULTS: Of 1318 eligible subjects, 1232 (93.4%) accepted the screening. Screening was completed by 993 (80.6%) individuals overall, 86.5% and 71.4% at the TBU and MHCU services, respectively. In a multivariate analysis model, the only variable associated with an increased probability of completing screening was being enrolled at the TBU site (OR 2.5, 95%CI 1.8-3.5; P < 0.001). Three hundred and ninety-two subjects (39.4%) had a TST test of > or = 10 mm. Eight cases of active tuberculosis were detected, with a calculated prevalence of disease of 650/100,000. CONCLUSIONS: Undocumented immigrants to Italy can be screened for TB at an unspecialised health service unit, although not as efficiently as at a specialised TB unit.     

Clustering of tuberculosis among senegalese immigrants in Italy.

OBJECTIVE: To study clustered Mycobacterium tuberculosis isolates as an indicator of recent TB transmission in a small urban setting in Italy, and to determine associated risk factors. METHODS: M. tuberculosis strains isolated between 1991 and 1997 were characterised by IS6110 restriction fragment length polymorphism (RFLP) analysis. RESULTS: One hundred and ninety-five isolates were available for RFLP analysis, which revealed 163 different patterns. Available cases were represented by 137 Italians (70%), 32 Senegalese (17%), and 26 other foreign-born cases (13%). A unique fingerprint pattern was found in 143 cases (73.3%), while 52 strains (26.7%) were grouped into 20 clusters. Nineteen cases (10%) were resident in the same quarter of Brescia with a high density of Senegalese immigrants (Area A). An increased probability of yielding clustered M. tuberculosis strains was associated with residence in Area A (OR 3.87, 95%CI 1.42-10.56; P = 0.02) and being Senegalese (OR = 5.96, 95%CI 1.48-23.97; P = 0.005). In the logistic regression analysis, being Senegalese was independently associated with yielding a clustered M. tuberculosis strain. CONCLUSIONS: Our results demonstrate a clustering of TB cases among Senegalese immigrants and suggest that RFLP analysis may be used to identify geographical areas where efforts can be targeted to interrupt TB transmission.     

Rituximab in children with resistant idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome resistant to standard treatments remains a therapeutic dilemma in pediatric nephrology. To test whether the anti-CD20 monoclonal antibody rituximab may benefit these patients, we conducted an open-label, randomized, controlled trial in 31 children with idiopathic nephrotic syndrome unresponsive to the combination of calcineurin inhibitors and prednisone. All children continued prednisone and calcineurin inhibitors at the doses prescribed before enrollment, and one treatment group received two doses of rituximab (375 mg/m(2) intravenously) as add-on therapy. The mean age was 8 years (range, 2-16 years). Rituximab did not reduce proteinuria at 3 months (change, -12% [95% confidence interval, -73% to 110%]; P=0.77 in analysis of covariance model adjusted for baseline proteinuria). Additional adjustment for previous remission and interaction terms (treatment by baseline proteinuria and treatment by previous remission) did not change the results. In conclusion, these data do not support the addition of rituximab to prednisone and calcineurin inhibitors in children with resistant idiopathic nephrotic syndrome.     

Short-Term Effects of Rituximab in Children with Steroid- and Calcineurin-Dependent Nephrotic Syndrome: A Randomized Controlled Trial

Summary

Background and objectives

Prednisone and calcineurin inhibitors are the mainstay therapy of idiopathic nephrotic syndrome (INS) in children. However, drug dependence and toxicity associated with protracted use are common. Case series suggest that the anti-CD20 monoclonal antibody rituximab (RTX) may maintain disease remission.

Design, setting, participants, & measurements

This open-label randomized controlled trial was powered to show that a strategy based on RTX and lower doses of prednisone and calcineurin inhibitors was noninferior to standard doses of these agents in maintaining 3-month proteinuria as low as baseline or up to 1 g/d greater (noninferiority margin). Participants were stratified by the presence of toxicity to prednisone/calcineurin inhibitors and centrally assigned to add RTX (Mabthera, 375 mg/m² intravenously) to lower doses of standard agents or to continue with current therapy alone. The risk of relapse was a secondary outcome.

Results

Fifty-four children (mean age 11 ± 4 years) with INS dependent on prednisone and calcineurin inhibitors for >12 months were randomized. Three-month proteinuria was 70% lower in the RTX arm (95% confidence interval 35% to 86%) as compared with standard therapy arm (intention-to-treat); relapse rates were 18.5% (intervention) and 48.1% (standard arm) (P = 0.029). Probabilities of being drug-free at 3 months were 62.9% and 3.7%, respectively (P < 0.001); 50% of RTX cases were in stable remission without drugs after 9 months.

Conclusions

Rituximab and lower doses of prednisone and calcineurin inhibitors are noninferior to standard therapy in maintaining short-term remission in children with INS dependent on both drugs and allow their temporary withdrawal.     

Liver biopsy discloses a new apolipoprotein A-I hereditary amyloidosis in several unrelated Italian families

BACKGROUND & AIMS: Hereditary systemic amyloidoses are autosomal dominant, late-onset disorders caused by mutations in the genes for a group of plasma proteins including transthyretin, lysozyme, fibrinogen Aalpha chain, gelsolin, apolipoprotein A-I, and apolipoprotein A-II. We investigated both phenotypic and genotypic aspects of apolipoprotein A-I amyloidosis unexpectedly disclosed by liver biopsy in 13 unrelated individuals with asymptomatic, persistent elevation of alkaline phosphatase and gamma-glutamyltransferase levels. METHODS: Immunoelectron microscopy was used for in situ characterization of amyloid deposits on liver biopsy specimens. Mutation analysis was performed by sequencing of the apolipoprotein A-I gene in all patients. Wild-type/variant apolipoprotein A-I ratio in plasma high-density lipoproteins was assessed by a peptide mass fingerprinting approach after purification of total apolipoprotein A-I of 2 patients. RESULTS: Family history was informative in 5 cases. Renal failure developed in 9 cases. Hypogonadism due to testicular involvement was observed. Amyloid fibrils specifically stained with anti-apolipoprotein A-I antibody. A novel (Leu75Pro) heterozygous mutation in the apolipoprotein A-I gene was present in affected individuals but not in controls. Variant apolipoprotein A-I was about 10% of the total protein in high-density lipoproteins. CONCLUSIONS: The high number of individuals with apparently sporadic disease might reflect widespread occurrence of this mutation in the population and a milder phenotype of this variant compared with other apolipoprotein A-I amyloidogenic mutants. These findings suggest that specific staining for amyloid should be performed on liver biopsy of individuals with asymptomatic chronic elevation of alkaline phosphatase and gamma-glutamyltransferase levels.