Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. RESULTS: Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. CONCLUSIONS: The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.

Mutational analysis in podocin-associated hereditary nephrotic syndrome in Polish patients: founder effect in the Kashubian population.

Hereditary nephrotic syndrome is caused by mutations in a number of different genes, the most common being NPHS2. The aim of the study was to identify the spectrum of NPHS2 mutations in Polish patients with the disease. A total of 141 children with steroid-resistant nephrotic syndrome (SRNS) were enrolled in the study. Mutational analysis included the entire coding sequence and intron boundaries of the NPHS2 gene. Restriction fragment length polymorphism (RFLP) and TaqMan genotyping assay were applied to detect selected NPHS2 sequence variants in 575 population-matched controls. Twenty patients (14 %) had homozygous or compound heterozygous NPHS2 mutations, the most frequent being c.1032delT found in 11 children and p.R138Q found in four patients. Carriers of the c.1032delT allele were exclusively found in the Pomeranian (Kashubian) region, suggesting a founder effect origin. The 14 % NPHS2 gene mutation detection rate is similar to that observed in other populations. The heterogeneity of mutations detected in the studied group confirms the requirement of genetic testing the entire NPHS2 coding sequence in Polish patients, with the exception of Kashubs, who should be initially screened for the c.1032delT deletion.

Determining levels of mineral consumption from foodstuff sources in the daily diets of adolescent students living in Kamien Pomorski. A pilot study.

BACKGROUND: In recent years, changes to adolescent life style and nutrition are becoming increasingly apparent. One of the ways in which this can be observed, is in an unbalanced daily intake of dietary minerals, where some intakes are in excess whilst others are deficient. Normal growth and development can thereby become adversely affected. OBJECTIVE: To determine daily dietary intake levels of calcium, magnesium, phosphorus, sodium, potassium, iron, zinc and copper together from their various foodstuff sources in the daily diet of a defined group of adolescents. MATERIAL AND METHODS: Subjects were adolescents aged 16-19 years attending the technical college at the Polish town of Kamien Pomorski; being under the jurisdiction of the Western Pomeranian Province (voivodship). The study tool was a survey of food that had been consumed within the last 24 hours, from which the amounts of mineral elements in any given menu, so chosen, could thus be estimated. RESULTS: Average daily potassium intakes were found to be generally low; less than 2350 mg and 1800 mg respectively for girls and boys compared to recommended values. This was coupled with high sodium intakes, where respectively, girls and boys exceeded recommended values by 2.1 and 2.8 times. Excess intakes of phosphorus, iron and copper were also observed in boys; respectively 500 mg, 4 mg and 2 mg. Some subjects showed insufficient intakes of calcium and magnesium i.e. 63%-80% below EAR (Estimated Average Requirements). The main source of calcium was found to be ripe cheeses, milk and fermented beverages. In both groups the main dietary sources of magnesium, sodium, iron and copper were bread. Girls diets showed that phosphorus and zinc mostly came from eating ripe cheeses and poultry, whereas potatoes were the main source of potassium. The boy's daily dietary intakes demonstrated that phosphorus and zinc originated from eating bread and potatoes. Significantly lower amounts of phosphorus, sodium, iron and zinc were however consumed by girls compared to boys. CONCLUSIONS: The mineral content of the subjects' daily diet was found to be substantially unbalanced.

Is dyslipidemia sustained during remission of nephrotic syndrome genetically determined? Evaluation of genetic polymorphisms of proteins involved in lipoprotein metabolism in children and adolescents with nephrotic syndrome.

INTRODUCTION: In same patients lipid profile disturbances persist during nephrotic syndrome remission. OBJECTIVES: The aim of the study was to evaluate the impact of the genetic polymorphisms of proteins involved in lipoprotein metabolism on persistent abnormal lipid profile in patients with nephrotic syndrome during remission. PATIENTS AND METHODS: 50 patients aged between 5.8 and 16.6 years (mean age 10.45 +/- 3.04) with nephrotic syndrome in remission of at least 8 weeks' duration, including 12 steroid-resistant and 38 steroid-dependent cases, participated in the study. We evalauated associations between lipid profile and genetic polymorphisms, V771M, V8251, and R1587K of the gene encoding the cassette ABCA1 (adenosine triphosphate binding cassette transporter A1) protein synthesis, a E3 polymorphism of the gene encoding the type upsilon of apolipoprotein E (apoE) synthesis and that of the gene encoding the cholesterol ester transfer protein (CETP) synthesis. RESULTS: Dyslipidemia was observed in 10/13 (76.9%) patients with V8251 polymorphism vs. 27/37 (73%) of non-carriers, and in 16/21 (76.2%) patients with R1587K polymorphism vs. 21/29 (72.4%) in the remaining subjects. V771M polymorphism was found only in 2 (4%) patients and one subject had abnormal lipid profile. In the presence of CETP gene polymorphism, hiperlipoproteinemia was detected in 22/31 (71%) vs. 15/19 (78.9%) in the remaining cases. The epsilon3epsilon3 apoE genotype (observed most commonly in the healthy population) was found in the majority (n=35; 70%) of patients. This genotype was also seen in most patients with abnormal serum lipid profile (in 26/37; 70.3%). Analysis of the whole population (ANOVA) did not show significant correlations between parameters of lipid profile and any of the polymorphisms studied. CONCLUSIONS: The study did not confirm associations between genetic polymorphisms of ABCA1 transporter, CETP and apoE and abnormal serum lipid profile during remission of nephrotic syndrome.

[Simvastatin therapy and effect on hiperlipidemia and vascular status in nephrotic children with sustained dyslipidemia]. / Wplyw simwastatyny na zaburzenia profilu lipidowego i stan naczyn tetniczych u dzieci z idiopatycznym zespolem nerczycowym.

UNLABELLED: Dyslipidemia is common in nephrotic children and persistent lipid abnormalities are risk factor of late vascular complications. The aim of the study was evaluation of efficacy and safety of 12-months simvastatin therapy in nephrotic children with lipid profile abnormalities present despite clinical remission lasting for at least 8 weeks, including ultrasonographic assessment of carotid and femoral arteries. MATERIAL AND METHODS: Overall 52 children (40 steroid-dependent and 12 steroid-resistant) were initially introduced to the study and 29 of them were treated with simvastatin. Normalisation of lipid profile was achieved in 19/29 (65.5%) and improvement in 9/29 (31%). Significant reduction in total cholesterol (p < 0.00001), LDL-C (p < 0.000003), VLDL- (p < 0.0123), oxy-LDL-C fractions (p < 0.0002) and triglycerides (TG) (p < 0.0005) serum concentration was achieved in non-proteinuric patients. RESULTS: Analysis of the intima-media thickness (IMT) of the common carotid (c) and superficial femoral (f) arteries values revealed positive correlation between baseline cIMT and VLDL-C (p = 0.038) and TG concentration (p = 0.008), as well as positive correlation between fIMT and baseline creatinine (p = 0.04) and LDL-C serum concentration (p = 0.032) after simvastatine treatment. Number of children with significant vessels pathology (Z-score > 2.0) was small. Increased cIMT was seen at baseline in 4 patients and in 5 after simvastatin treatment, however average and Z-score values in children under simvastatin treatment have decreased. Increased fIMT values were seen at baseline in 2 and in one case after simvastatin treatment. Tolerance of simvastation was very good in all cases but one. CONCLUSION: Simvastatin therapy was effective and safe in nephrotic non-proteinuric children with abnormal lipid profile. Fair estimation of impact of the 12-months simvastatin therapy on vascular status was not available due to limited number of children with significantly increased IMT at baseline.

[Evaluation of arterial intima-media thickness (IMT) in children with idiopathic nephrotic syndrome--preliminary report]. / Ocena grubosci kompleksu blona wewnetrzna-blona srodkowa naczyn tetniczych u dzieci z idiopatycznym zespolem nerczycowym--doniesienie wstepne.

UNLABELLED: One the complications of idiopathic nephrotic syndrome (i.n.s.) is long-lasting lipid unfavourable lipid profile, a risk factor of early atherosclerosis. Aim of the study was evaluation of the incidence of early signs of atheromathosis in children with INS expressed as the increased IMT in the (elastic) common carotid (cIMT) and (muscular) superficial femoral ((fIMT) arteries. The study included 50 children (34 boys and 16 girls) aged from 5.83 to 16.58 y (mean 10,8) with INS Overall duration of the disease ranged from 2.58 to 13.83 y (mean 7.81) [in 23 (46%) children < 10 yrs mean 6.21 yrs; in 16 (32%) from 10 to 14 yrs mean 11.93 yrs and in 11 (22%) >14 yrs mean 4.27 yrs]. 16 children were treated with prednisone, 32 with cyclosporine A (CsA) and 2 mycophenolate mofetil (MMF). The renal function in 49 children was normal and decreased in 1 case. Children treated with CsA and MMF received renoprotection with enalapril or enalapril/losartan. USG technique was used to evaluate cIMT and fIMT. In 39 (78%) pts, 26/34 (76.47%) > and 13/16 (81.25%) + cIMT was increased. fIMT was increased in 13 (26%) pts, including 12/34 (35.29%) > and 1/16 (6.25%) +. Among pts <10y. of age cIMT was increased in 19/23 (82.6%) and fIMT in 5/23 (21.73%). Among pts between 10-14 yrs cIMT was increased in 13/16 (81.25%), and fIMT in 4/16 (25%). Among pts >14 yrs cIMT was increased in 7/11 (63.63%), and fIMT in 4 (36,36%) cases. CONCLUSION: Increased intima-media thickness in (elastic) carotid artery was shown in vast majority of children with nephrotic syndrome.