Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease

Zagury, Alberto; Oliveira, Anne Louise de; Montalvão, Jose Augusto Araujo; Novaes, Regina Helena Leite Lemos; Sá, Vinicius Martins de; Moraes, Carlos Augusto Pinheiro de; Tavares, Marcelo de Sousa

doi:10.5935/0101-2800.20130031

Cited by 60 publications

(48 citation statements)

References 36 publications

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“…Children with NS are a population at risk for progressive CKD, particularly children with SRNS who have a 5-year renal survival rate of 72%-94% (26,27). Recently, there has been increasing recognition that AKI is a risk factor for development and progression of CKD in children (28,29).…”

Section: Discussionmentioning

confidence: 99%

AKI in Children Hospitalized with Nephrotic Syndrome

Rheault¹,

Zhang²,

Selewski³

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome.Design, setting, participants, & measurements Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition.Results AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P,0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P,0.001).Conclusions AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.

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Section: Discussionmentioning

confidence: 99%

AKI in Children Hospitalized with Nephrotic Syndrome

Rheault¹,

Zhang²,

Selewski³

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Steroid-resistant nephrotic syndrome (SRNS) is a challenging clinical condition with highly variable outcomes, and 50% of children progress to ESRD within 15 years (3,4). Although in some patients, temporary or persistent remission is achieved by intensified immunosuppressive therapies (IITs), others exhibit a multidrug-resistant phenotype.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children

Trautmann¹,

Bodria²,

Özaltın³

et al. 2015

Clinical Journal of the American Society of Nephrology

242

229

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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.

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“…1 Most children with idiopathic NS respond well to steroids, but 10%-20% of affected children are categorized as having steroid-resistant NS (SRNS). [2][3][4][5][6] SRNS is a clinically and genetically heterogeneous renal disorder that might have an immunological, structural, or functional etiology. 2,5,[7][8][9] Higher rates of genetic delineation are expected in earlyonset SRNS.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, 63%-73% of those with childhoodonset SRNS show pathologically focal segmental glomerulosclerosis (FSGS),which carries a great risk of progression to end-stage renal disease (ESRD). 1,6,8,10 To date, at least 27 genes are associated with SRNS, thereby expanding our knowledge of the pathomechanisms involved in SRNS and podocyte development and function. 11 Although SRNS is the leading cause of ESRD in children worldwide, approximately 70% of those with childhood-onset SRNS are genetically uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

Biallelic Mutations in Nuclear Pore Complex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome

Miyake

Tsukaguchi

Koshimizu

et al. 2015

The American Journal of Human Genetics

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The nuclear pore complex (NPC) is a huge protein complex embedded in the nuclear envelope. It has central functions in nucleocytoplasmic transport, nuclear framework, and gene regulation. Nucleoporin 107 kDa (NUP107) is a component of the NPC central scaffold and is an essential protein in all eukaryotic cells. Here, we report on biallelic NUP107 mutations in nine affected individuals who are from five unrelated families and show early-onset steroid-resistant nephrotic syndrome (SRNS). These individuals have pathologically focal segmental glomerulosclerosis, a condition that leads to end-stage renal disease with high frequency. NUP107 is ubiquitously expressed, including in glomerular podocytes. Three of four NUP107 mutations detected in the affected individuals hamper NUP107 binding to NUP133 (nucleoporin 133 kDa) and NUP107 incorporation into NPCs in vitro. Zebrafish with nup107 knockdown generated by morpholino oligonucleotides displayed hypoplastic glomerulus structures and abnormal podocyte foot processes, thereby mimicking the pathological changes seen in the kidneys of the SRNS individuals with NUP107 mutations. Considering the unique properties of the podocyte (highly differentiated foot-process architecture and slit membrane and the inability to regenerate), we propose a "podocyte-injury model" as the pathomechanism for SRNS due to biallelic NUP107 mutations.

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Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease

Abstract: Our findings showed that CsA-resistance and FSGS were risk factors for ESRD.

Cited by 60 publications

References 36 publications

AKI in Children Hospitalized with Nephrotic Syndrome

AKI in Children Hospitalized with Nephrotic Syndrome

Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children

Biallelic Mutations in Nuclear Pore Complex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome

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