scholarly journals Treatment of Steroid and Cyclosporine-Resistant Idiopathic Nephrotic Syndrome in Children

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
A. A. Nikibakhsh ◽  
H. Mahmoodzadeh ◽  
M. Karamyyar ◽  
S. Hejazi ◽  
M. Noroozi ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Complete Remission ◽  
Partial Remission ◽  
Significant Risk ◽  
Second Step ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Risk Of Progression ◽  
End Stage ◽  
Total Remission

Steroid-resistant nephrotic syndrome (SRNS) in children carries a significant risk of progression to end-stage renal failure (ESRF). We report a two-step protocol adapted in children with SRNS. Thirty-seven SRNS were treated with cyclosporine A (CyA) in association with prednisolone (alternate day) for 6 months (first-step treatment). Twelve patients (32.4%) went into complete remission, and 2 (5.4%) got partial remission. The other 23 cases who were steroid and CyA resistant entered a second-step treatment with withdrawing steroids, with CyA (5 mg/kg/day) in association with mycophenolate mofetil (MMF) 30 mg/kg/day for 6 months. Complete remission was observed in 11 cases (47.82%) and partial remission in 2 cases (8.7%). After two steps of treatment, 27/37 children went into total remission. In steroid and CyA-resistant INS, the association of MMF with CyA was able to induce remission in about half cases without relevant side effects.

scholarly journals NPHS2 gene mutation, atopy, and gender as risk factors for steroid-resistant nephrotic syndrome in Indonesians

2011 ◽  
Vol 51 (5) ◽  
pp. 272 ◽  
Author(s):  
Dedi Rachmadi ◽  
Danny Hilmanto ◽  
Ponpon Ijradinata ◽  
Abdurahman Sukadi
Keyword(s):  
Risk Factors ◽  
Nephrotic Syndrome ◽  
Gene Mutation ◽  
Significant Risk ◽  
Gene Mutations ◽  
Male Gender ◽  
Amplification Refractory Mutation System ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Nphs2 Gene

Background Steroid-resistant nephrotic syndrome (SRNS) often develops into end stage renal disease. Previous studies have reported that NPHS2 gene mutation, gender, and atopic history are risk factors associated with SRNS. Interethnic, sociocultural, and environmental differences have also been suggested to affect these mutations.Objective To analyze possible risk factors for SRNS, including NPHS2 gene mutations (412C→T and 419delG), gender and atopic history, in Indonesian subjects with SRNS.Methods A case-control study with 153 subjects, consisting of 88 SRNS patients and 65 control subjects, was undertaken in 10 Indonesian teaching centre hospitals from September 2006 to December 2007. Analysis of the NPHS2 gene mutation in 412 C→T was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), while that for the NPHS2 gene mutation in 419delG was performed by restriction fragment length polymorphism (RFLP). Data was analyzed by multiple logistic regression.Results In our Indonesian subjects, the significant risk factors for SRNS were male gender (OR=2.21; CI 95%:1.07-4.56, P=0.036), NPHS2 412C→T gene mutation (OR=18.07; CI 95%:6.76-48.31, P<0.001), and NPHS2 419delG gene mutation (OR=4.55; CI 95%:1.66-12.47, P=0.003). However, atopic history was not a significant risk factor for SRNS (OR=1.807; CI 95%:0.642-5.086, P=0.262).Conclusion NPHS2 412C→T and 419delG gene mutations, as well as male gender are risk factors for SRNS in Indonesian subjects. Atopic history was not significantly associated with SRNS in our subjects. [Paediatr Indones. 2011;51:272-6].

scholarly journals Mutations in NPHS2 Encoding Podocin Are a Prevalent Cause of Steroid-Resistant Nephrotic Syndrome among Israeli-Arab Children

2002 ◽  
Vol 13 (2) ◽  
pp. 400-405 ◽  
Author(s):  
Yaacov Frishberg ◽  
Choni Rinat ◽  
Orli Megged ◽  
Eli Shapira ◽  
Sofia Feinstein ◽  
...  
Keyword(s):  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
End Stage Renal Failure ◽  
Arab Children ◽  
Presenting Symptoms ◽  
End Stage ◽  
Arab Descent

ABSTRACT. Steroid-resistant nephrotic syndrome (SRNS) represents a heterogeneous group of kidney disorders that are often resistant to other immunosuppressive agents and tend to progress to end-stage renal failure. Mutations in the gene NPHS2 that encode a protein named podocin have recently been found in a recessive form of SRNS. Ten children from two inbred families of Israeli-Arab descent presented with SRNS. Renal histologic findings were of diffuse mesangial proliferation. Six patients reached end-stage renal failure, but nephrotic syndrome did not recur after renal transplantation. Mutation analysis of NPHS2 revealed that they were homozygous for the C412T mutation (R138X). Eighteen children were subsequently analyzed with SRNS due to biopsy-proven focal segmental glomerulosclerosis (FSGS) from unrelated families of Israeli-Arab descent. Analysis disclosed six additional patients (33%) bearing the same mutation in a homozygous pattern. Three of them had no affected relatives, although they came from large families. Taken together, of the 27 patients tested (familial and nonfamilial), 15 patients (55%) were homozygous for the mutation (R138X). They all shared the same haplotype and were homozygous for the A1023G polymorphism, thus pointing to a possible founder effect. Thirteen children of Israeli-Jewish origin with SRNS and biopsy-proven FSGS and 15 children of both ethnic groups with steroid-responsive FSGS were tested, and none was found to have mutations in NPHS2. The results of this study demonstrate that mutations in NPHS2 are a common cause of SRNS in Israeli-Arab children. Mutations in NPHS2 may cause SRNS in nonfamilial cases. The interethnic differences in the occurrence of NPHS2 mutations may explain, in part, the previous observation that Arab patients with FSGS in Israel have a worse prognosis as compared with Jewish patients, despite similar presenting symptoms and medical management. Identifying the causing mutation will enable clinicians to avoid unnecessary immunosuppressive therapeutic trials in newly diagnosed patients and to provide prenatal diagnosis to families at risk.

The New Compound Heterozygous Mutation of NUP Nephropathy: Report of Two Cases and Literature Review

2021 ◽  
Author(s):  
Yuxin Pei ◽  
Liping Rong ◽  
Mengjie Jiang ◽  
Zhilang Lin ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Literature Review ◽  
End Stage Renal Disease ◽  
Compound Heterozygous ◽  
Founder Mutations ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Renal Manifestation ◽  
Stage Renal Disease ◽  
End Stage

Abstract Backgrounds: NUP nephropathy is identified as a rare monogenic cause of steroid-resistant nephrotic syndrome recently. To explore the relationship between NUP mutation and renal disorders, we provide two cases and a literature review of the genotypical and phenotypical features in patients with NUP nephropathy.Results: We reported two patients with newly diagnosed NUP nephropathy who carried a compound heterozygous mutations in NUP107 and NUP93 gene respectively. Both patients were diagnosed steroid-resistant nephrotic syndrome and progressed to end-stage renal disease in childhood. While the mutation c.1537+1G>A in NUP93 gene was previously described, the mutations c.460A>G and c.1085C>T in NUP107 gene and c.1472A>T in NUP93 gene were novel. We also summarized the phenotypic and genetic spectrum of NUP nephropathy in eighty-six reported patients who carried 50 different mutations in 6 NUP genes (NUP107, NUP93, NUP205, NUP85, NUP133, NUP160). The majority of them were Asians (66/86, 76.7%). The mutation c.2492A>C and c.1079-1083del in NUP107 had been identified as the founder mutations in East Asian[1-3], while c.1772G>T and c.1886A>G in NUP93 might be the founder mutations in Western Europe and Turkish respectively. Nephrotic syndrome was the most common renal manifestation (68/86, 79.1%). Although the renal prognosis was poor that 80.8% (59/73) of them developed end-stage renal disease within the first two decades, the outcome of renal transplantation in NUP nephropathy is better than patients with other steroid-resistant nephrotic syndrome. Focal segmental glomerulosclerosis was the most prevalent renal biopsy pathologic type (56/65, 86.1%). Various extra-renal manifestations were found in 44.8% (26/58) of patients. Neurological involvement was the most common extra-renal presentation (22/26, 84.6%), including microcephaly (13/22, 59.1%), intellectual disability (12/22, 54.5%), and global developmental delay (10/22, 45.5%). Diverse abnormalities of the facial appearance (8/26, 30.8%), short stature (5/26, 19.2%),and contain convergent strabismus (4/26, 15.4%) had also been reported. There are significant differences in extra-renal manifestations between different genomics. Conclusions: The renal manifestation of NUP nephropathy is highly consistent that most patients suffered early-onset SRNS with FSGS. More than half of the patients had extra-renal symptom concomitantly. Asians showed potential susceptibility to NUP nephropathy. Despite the limited reports, some genotype-phenotype correlations have been gradually revealed.

scholarly journals The importance of genetic study in steroid-resistant nephrotic syndrome

2019 ◽  
Vol 8 (4) ◽  
pp. 271-282 ◽  
Author(s):  
Sepideh Zununi Vahed ◽  
Hakimeh Moghaddas Sani ◽  
Sima Rajabzadeh ◽  
Ziba Nariman-Saleh-Fam ◽  
Mina Hejazian ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Therapeutic Benefit ◽  
Steroid Resistance ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Filtration Barrier ◽  
Stage Renal Disease ◽  
End Stage

Steroid-resistant nephrotic syndrome (SRNS) is a challenging clinical task. It has heterogeneous etiology and extremely variable clinical outcomes and generally progresses to end-stage renal disease (ESRD). Different gene mutations in podocyte’s slit diaphragm, mitochondria, and cytoskeleton proteins, as well as glomerular basement membrane (GBM) have been associated with SRNS. These proteins regulate the function of the glomerular filtration barrier. Advances in genetic approaches and podocytology have led to discover the SRNS-causing genes that lead to a better understanding of the drug resistance. More than 45 genetic mutations have been recognized in the hereditary form of SRNS. This review offers an update on the current knowledge of steroid resistance-causing gene mutations in podocytes. Understanding the specific genes involved in SRNS would guarantee an optimum therapeutic benefit of steroid treatment.

scholarly journals Novel Mutations in NPHS2 Detected in Both Familial and Sporadic Steroid-Resistant Nephrotic Syndrome

2002 ◽  
Vol 13 (2) ◽  
pp. 388-393 ◽  
Author(s):  
Stephanie M. Karle ◽  
Barbara Uetz ◽  
Vera Ronner ◽  
Lisa Glaeser ◽  
Friedhelm Hildebrandt ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Positional Cloning ◽  
Mutational Analysis ◽  
Causative Gene ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACT. Autosomal recessive steroid-resistant nephrotic syndrome (SRINS) belongs to the heterogeneous group of familial nephrotic syndrome and represents a frequent cause of end-stage renal disease in childhood. This kidney disorder is characterized by early onset of proteinuria, progression to end-stage renal disease, and histologic findings of focal segmental glomerulosclerosis, minimal change nephrotic syndrome, or both. A causative gene, NPHS2, has been mapped to chromosome 1q25-q31 and was recently identified by positional cloning. This study reports five novel NPHS2 mutations: A284V, R196P, V290M, IVS4-1G→T, and 460-467insT in 12 (46%) of 26 multiplex families and in 7 (28%) of 25 single patients with the clinical diagnosis of a SRINS. Because NPHS2 mutations were found in nearly 30% of these patients with “sporadic” SRINS, mutational analysis should also be performed in these patients. Besides better classification of the disease entity, identification of NPHS2 mutations may save some of these patients from unnecessary steroid treatment and also permit the prediction of absence of disease recurrence after kidney transplantation.

scholarly journals Congenital nephrotic syndrome may respond to cyclosporine A: A case report and review of literature

2017 ◽  
Vol 145 (7-8) ◽  
pp. 407-410 ◽  
Author(s):  
Bilsana Mulic ◽  
Gordana Milosevski-Lomic ◽  
Dusan Paripovic ◽  
Divna Kruscic ◽  
Mersudin Mulic ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Cyclosporine A ◽  
Partial Remission ◽  
Enzyme Inhibitor ◽  
Severe Disease ◽  
Congenital Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Long Term Effect ◽  
Intravenous Gamma Globulin

Introduction. Congenital nephrotic syndrome (CNF) is manifested at birth or within the first three months of life. The Finnish-type of CNF is caused by the mutation of the NPHS1 gene, which encodes nephrin in the podocyte slit diaphragm. It is a very severe disease, for which immunosuppressive therapy is not advised. Here we describe a patient with CNF who responded to CsA by partial remission. Case outline. A girl aged 2.5 months presented with severe non-syndromic steroid-resistant nephrotic syndrome. She needed aggressive support including daily albumin infusions and diuretics. Substitution of vitamin D, thyroxin, and anticoagulants were regularly administered. She was also treated with angiotensin converting enzyme inhibitor, without clear benefits regarding proteinuria. In addition, she received intravenous gamma-globulin replacement therapy and antibiotics during frequent infections. While waiting for the results of genetic analyses and faced with many problems related to daily albumin infusions, infections, and thromboembolic complications, cyclosporine A (CsA) was introduced as an alternative to early nephrectomy and consequent renal failure. The patient responded by partial remission and CsA treatment continued at home without the albumin infusions. After almost five years since the beginning of the treatment, the patient?s renal function remains unreduced. Conclusion. Our case demonstrates that CsA can induce partial remission in patients with genetic forms of steroid-resistant nephrotic syndrome without influencing the glomerular filtration rate. However, its long-term effect and safety should carefully be monitored.

scholarly journals Prognostic factors and survivals of children with steroid-resistant nephrotic syndrome

2013 ◽  
Vol 53 (1) ◽  
pp. 42
Author(s):  
Partini Pudjiastuti Trihono ◽  
Nina Dwi Putri ◽  
Aman B Pulungan
Keyword(s):  
Nephrotic Syndrome ◽  
Cohort Study ◽  
Kidney Function ◽  
Medical Records ◽  
Retrospective Cohort ◽  
Age At Onset ◽  
Survival Rates ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
End Stage

Background Children with steroid resistant nephrotic syndrome(SRNS) generally survive, although during the course of diseasetheir kidney function may decrease, leading to end-stage renaldisease (ESRD). There have been few studies reporting on thesurvivals of children with SRNS.Objectives To determine patient and kidney survival rates in childrenwith SRNS at the first, second, third, fourth, and fifth years; and toevaluate the effects of age at onset, initial kidney function, hypertension,and type of resistance, on the survivals of children with SRNS.Methods This retrospective cohort study was performed usingsecondary data obtained from medical records of patients with SRNS inDepartment of Child Health, Cipto Mangunkusumo Hospira~ between2004-2011. The outcomes of kidney survivals were defined in two ways:lack of doubling of base creatinine levels and lack of ESRD.Results There were 45 children with SRNS in our study. Their medianduration ofillness was 24 (range 12-95) months. Twenty percent of thesubjects died, 31.1 % had a doublingofbase creatinine levels, and 13.4%developed ESRD. Life survival rates of subjects at the first, second,third, fourth, and fifth years after diagnosis were 93 %, 84%, 80"/ri, 7 2%,and 61 %, respectively. Kidney survival rates determined by the lackof doubling of base creatinine levels at the first, second, third, fourthand fifth years were 92%, 72%, 56%, 42%, and 34%, respectively, whilekidney survival rates determined by the lack ofESRD were 97%, 88%,81 %, 70"/o, and 58%, respectively. Age at onset, initial kidney function,hypertension at onset, and type of resistance, did not significantly affectthe survivals of children with SRNS.Conclusion Children with SRNS are prone to develop a doublingof base creatinine levels and ESRD. Factors such as age, initialkidney function, hypertension at onset, and type ofresistance, donot significantly affect both, life and kidney survivals of childrenwith SRNS.

scholarly journals Look Alike, Sound Alike: Phenocopies in Steroid-Resistant Nephrotic Syndrome

2020 ◽  
Vol 17 (22) ◽  
pp. 8363
Author(s):  
Francesca Becherucci ◽  
Samuela Landini ◽  
Luigi Cirillo ◽  
Benedetta Mazzinghi ◽  
Paola Romagnani
Keyword(s):  
Nephrotic Syndrome ◽  
Genetic Testing ◽  
Clinical Management ◽  
Reverse Genetics ◽  
Molecular Mechanisms ◽  
Young Patients ◽  
Diagnostic Procedures ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
End Stage

Steroid-resistant nephrotic syndrome (SRNS) is a clinical picture defined by the lack of response to standard steroid treatment, frequently progressing toward end-stage kidney disease. The genetic basis of SRNS has been thoroughly explored since the end of the 1990s and especially with the advent of next-generation sequencing. Genetic forms represent about 30% of cases of SRNS. However, recent evidence supports the hypothesis that “phenocopies” could account for a non-negligible fraction of SRNS patients who are currently classified as non-genetic, paving the way for a more comprehensive understanding of the genetic background of the disease. The identification of phenocopies is mandatory in order to provide patients with appropriate clinical management and to inform therapy. Extended genetic testing including phenocopy genes, coupled with reverse phenotyping, is recommended for all young patients with SRNS to avoid unnecessary and potentially harmful diagnostic procedures and treatment, and for the reclassification of the disease. The aim of this work is to review the main steps of the evolution of genetic testing in SRNS, demonstrating how a paradigm shifting from “forward” to “reverse” genetics could significantly improve the identification of the molecular mechanisms of the disease, as well as the overall clinical management of affected patients.

scholarly journals Prevalence, Genetics, and Clinical Features of Patients Carrying Podocin Mutations in Steroid-Resistant Nonfamilial Focal Segmental Glomerulosclerosis

2001 ◽  
Vol 12 (12) ◽  
pp. 2742-2746 ◽  
Author(s):  
Gianluca Caridi ◽  
Roberta Bertelli ◽  
Alba Carrea ◽  
Marco Di Duca ◽  
Paolo Catarsi ◽  
...  
Keyword(s):  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Founder Effect ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
End Stage Renal Failure ◽  
Segmental Glomerulosclerosis ◽  
End Stage ◽  
Nphs2 Gene

ABSTRACT. Podocin mutations (NPHS2 gene) are responsible for the autosomal recessive form of steroid-resistant nephrotic syndrome. As a result of a screening for these gene alterations in a cohort of Italian patients with nonfamilial nephrotic syndrome and histologic focal segmental glomerulosclerosis (FSGS), nine patients with NPHS2 gene homozygous or composite heterozygous mutations were found. In addition to the previously described defects, two novel mutations at exon 4 were identified (frameshift, L169P); four single nucleotide polymorphisms (SNPs) and one dinucleotide repeat were also identified. On the basis of haplotype analysis, a founder effect was suggested for the 419delG mutation, the most frequently observed in the patients studied. Patients carrying NPHS2 mutations and without a family history of nephrotic syndrome were indistinguishable from those with idiopathic FSGS on the basis of the clinical phenotype. Two of the nine patients had normal renal function at 3 and 10 yr of age, despite the presence of the nephrotic syndrome. The other seven had reached end-stage renal failure at a mean age of 9.6 yr (range, 4 to 17 yr) and had received renal allografts. In those presenting with end-stage renal failure, the clinical and laboratory features both before and after transplantation were similar, including the age at onset, the amount of proteinuria, and the absence of any response to steroids and other immunosuppressants. Finally, two children presented recurrence of mild proteinuria after transplantation, which promptly remitted after plasmapheresis combined with cyclophosphamide. These data demonstrate that podocin mutations in nonfamilial cases of steroid-resistant nephrotic syndrome are frequent and may be due in one case to a founder effect. The pretransplantation and posttransplantation outcomes in the group of patients with mutations of the podocin gene are similar to classical idiopathic FSGS, including the possibility of recurrence of proteinuria that is mild and responsive to plasmapheresis. These observations support a role of molecular screening of the podocin gene in patients with nephrotic syndrome before immunosuppressive treatment is started.

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