scholarly journals Intravenous cyclophosphamide induces remission in children with difficult to treat steroid resistant nephrotic syndrome from minimal change disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Maha Haddad ◽  
Arundhati Kale ◽  
Lavjay Butani
Keyword(s):  
Nephrotic Syndrome ◽  
North American ◽  
Minimal Change Disease ◽  
Immunosuppressive Agents ◽  
Laboratory Data ◽  
Minimal Change ◽  
Indian Children ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
American Children

Abstract Background Steroid resistant nephrotic syndrome (SRNS), while uncommon in children, is associated with significant morbidity. Calcineurin inhibitors (CNIs) remain the first line recommended therapy for children with non-genetic forms of SRNS, but some children fail to respond to them. Intravenous (IV) cyclophosphamide (CTX) has been shown to be effective in Asian-Indian children with difficult to treat SRNS (SRNS-DTT). Our study evaluated the outcome of IV CTX treatment in North American children with SRNS-DTT. Methods Retrospective review of the medical records of children with SRNS-DTT treated with IV CTX from January 2000 to July 2019 at our center. Data abstracted included demographics, histopathology on renal biopsy, prior and concomitant use of other immunosuppressive agents and serial clinical/laboratory data. Primary outcome measure was attainment of complete remission (CR). Results Eight children with SRNS-DTT received monthly doses (median 6; range 4–6) of IV CTX. Four (50%) went into CR, 1 achieved partial remission and 3 did not respond. Three of the 4 responders had minimal change disease (MCD). Excluding the 1 child who responded after the 4th infusion, the median time to CR was 6.5 (range 0.5–8) months after completion of IV CTX infusions. Three remain in CR at a median of 8.5 years (range: 3.7–10.5 years) after completion of CTX; one child relapsed and became steroid-dependent. No infections or life-threatening complications related to IV CTX were observed. Conclusions IV CXT can induce long term remission in North-American children with MCD who have SRNS-DTT.

scholarly journals Intravenous Cyclophosphamide Induces Remission in Children with Difficult to Treat Steroid Resistant Nephrotic Syndrome from Minimal Change Disease

2021 ◽  
Author(s):  
Maha Haddad ◽  
Arun Kale ◽  
Lavjay Butani
Keyword(s):  
Nephrotic Syndrome ◽  
North American ◽  
Minimal Change Disease ◽  
Immunosuppressive Agents ◽  
Laboratory Data ◽  
Minimal Change ◽  
Indian Children ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
American Children

Abstract Background: Steroid resistant nephrotic syndrome (SRNS), while uncommon in children, is associated with significant morbidity. Calcineurin inhibitors (CNIs) remain the first line recommended therapy for children with non-genetic forms of SRNS, but some children fail to respond to them. Intravenous (IV) cyclophosphamide (CTX) has been shown to be effective in Asian-Indian children with difficult to treat SRNS (SRNS-DTT). Our study evaluated the outcome of IV CTX treatment in North American children with SRNS-DTT.Methods: Retrospective review of the medical records of children with SRNS-DTT treated with IV CTX from January 2000 to July 2019 at our center. Data abstracted included demographics, histopathology on renal biopsy, prior and concomitant use of other immunosuppressive agents and serial clinical/laboratory data. Primary outcome measure was attainment of complete remission (CR). Results: Eight children with SRNS-DTT received monthly doses (median 6; range 4-6) of IV CTX. Four (50%) went into CR, 1 achieved partial remission and 3 did not respond. Three of the 4 responders had minimal change disease (MCD). Excluding the 1 child who responded after the 4th infusion, the median time to CR was 6.5 (range 0.5-8) months after completion of IV CTX infusions. Three remain in CR at a median of 8.5 years (range: 3.7-10.5 years) after completion of CTX; one child relapsed and became steroid-dependent. No infections or life-threatening complications related to IV CTX were observed.Conclusions: IV CXT can induce long term remission in North-American children with MCD who have SRNS-DTT.

scholarly journals Complications and renal biopsy profile in childhood steroid resistant nephrotic syndrome

2020 ◽  
Vol 7 (6) ◽  
pp. 1420
Author(s):  
Subramani Palaniyandi ◽  
Anitha Palaniyandi
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Minimal Change Disease ◽  
Disease Incidence ◽  
Early Morning ◽  
Minimal Change ◽  
Observation Study ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Urine Albumin

Background: Nephrotic syndrome is a notable chronic disease in children. The objective of this study was to study the complications and renal biopsy profile in childhood steroid resistant nephrotic syndrome.Methods: Retrospective observation study done in Sri Ramachandra Medical College and Hospital, Department of Paediatrics, Chennai. Inclusion criteria was children aged 1-12 years diagnosed with steroid resistant nephrotic syndrome defined as absence of remission despite therapy with daily prednisolone at a dose of 2mg/kg/day for 4 weeks. Remission defined as urine albumin nil/trace in 3 consecutive early morning samples. Children less than 1 year of age, children with renal transplant and incomplete records were excluded. Period of study January 2013- December 2015. Informed consent was obtained and 75 cases who fulfilled the study criteria were included in this study. Variables assessed were incidence of hypertension (both at onset of disease and later during the course of disease), incidence of urinary tract infection and its microbiology, associated co-morbidities, complications of nephrotic syndrome and renal biopsy profile.Results: Incidence of hypertension at onset of disease was 13.3% and later during the course of the disease was 48%. Most common infection was UTI (28%) and the most common organism isolated in urine culture was E-coli. Incidence of other co-morbidities like asthma, atopy was 17.3%. No case had evidence of end stage renal disease. 60% of cases had undergone renal biopsy and minimal change disease was the most common biopsy finding.Conclusions: Hypertension and UTI remain important complications in nephrotic syndrome and hence all such children should be continued to be monitored for these complications. Minimal change disease (MCD) was the most common renal biopsy finding.

scholarly journals Clinical manifestations of focal segmental glomerulosclerosis in Japan from the Japan Renal Biopsy Registry: age stratification and comparison with minimal change disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takaya Ozeki ◽  
Shoichi Maruyama ◽  
Toshiyuki Imasawa ◽  
Takehiko Kawaguchi ◽  
Hiroshi Kitamura ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Clinical Diagnosis ◽  
Clinical Characteristics ◽  
Minimal Change Disease ◽  
Multivariable Analysis ◽  
Laboratory Data ◽  
Minimal Change ◽  
Segmental Glomerulosclerosis

AbstractFocal segmental glomerulosclerosis (FSGS) is a serious condition leading to kidney failure. We aimed to investigate the clinical characteristics of FSGS and its differences compared with minimal change disease (MCD) using cross-sectional data from the Japan Renal Biopsy Registry. In Analysis 1, primary FSGS (n = 996) were stratified by age into three groups: pediatric (< 18 years), adult (18–64 years), and elderly (≥ 65 years), and clinical characteristics were compared. Clinical diagnosis of nephrotic syndrome (NS) was given to 73.5% (97/132) of the pediatric, 41.2% (256/622) of the adult, and 65.7% (159/242) of the elderly group. In Analysis 2, primary FSGS (n = 306) and MCD (n = 1303) whose clinical diagnosis was nephrotic syndrome (NS) and laboratory data were consistent with NS, were enrolled. Logistic regression analysis was conducted to elucidate the variables which can distinguish FSGS from MCD. On multivariable analysis, higher systolic blood pressure, higher serum albumin, lower eGFR, and presence of hematuria associated with FSGS. In Japanese nationwide registry, primary FSGS patients aged 18–64 years showed lower rate of NS than those in other ages. Among primary nephrotic cases, FSGS showed distinct clinical features from MCD.

scholarly journals P1802EVALUATION OF THE GENETICAL FEATURES AFFECTING THE RENAL OUTCOMES IN CHILDREN WITH STEROID RESISTANT NEPHROTIC SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Elif Comak ◽  
Aslı Toylu ◽  
Ugur Bilge ◽  
Gülsah Kaya Aksoy ◽  
Mustafa Koyun ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Target Genes ◽  
Immunosuppressive Agents ◽  
Gene Panel ◽  
Sequencing Analysis ◽  
Single Nucleotide Variants ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Genes Encoding ◽  
Renal Prognosis

Abstract Background and Aims Nephrotic syndrome in childhood is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Although most children respond to glucocorticoid therapy, approximately 10% of patients turn out to be steroid resistant (steroid-resistant nephrotic syndrome [SRNS]). Although several studies in children with SRNS have shown that mutations in genes encoding proteins in the podocyte skeleton may be responsible for the etiology in only one-third of cases, the genetic features related with renal prognosis and response to immunosuppressive agents are not fully recognized. The aim of this study was to investigate the genomic alterations associated with renal prognosis and resistance to immunosuppression in children with SRNS. Method The children with SRNS were enrolled in this study. Custom gene panel was designed for next-generation sequencing analysis of more than 20 target genes (ABCB1, ABCC2, CTLA4, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, FOXP3, GSTP1, IMPDH1, IMPDH2, NOS3, NR3C1, SLCO1B1, SLCO1B3, TPMT, UGT1A9, UGT2B7) and 200 single nucleotide variants (SNVs) which were reported as implicated in renal prognosis of nephrotic syndrome. The target gene panel was enriched for drug metabolism regulating transporters and enzymes. Results A total of 25 children, 16 boys (64%), median age at last visit 17.5 years (13-18 years), median age at diagnosis 7.5 years (2-15), median follow-up 9.58±4.54 years, were included in the study. All patients were diagnosed focal segmental glomerulosclerosis on renal biopsy.

scholarly journals Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome

2008 ◽  
Vol 23 (9) ◽  
pp. 1455-1460 ◽  
Author(s):  
Gil Chernin ◽  
Saskia F. Heeringa ◽  
Rasheed Gbadegesin ◽  
Jinhong Liu ◽  
Bernward G. Hinkes ◽  
...  
Keyword(s):  
African American ◽  
Nephrotic Syndrome ◽  
African American Children ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
American Children ◽  
Low Prevalence ◽  
Nphs2 Mutations

scholarly journals Plasmapheresis-induced Clinical Improvement in a Patient with Steroid-Resistant Nephrotic Syndrome Due to Podocin (NPHS2) Gene Station

2010 ◽  
Vol 53 (3) ◽  
pp. 157-159 ◽  
Author(s):  
Sylva Skálová ◽  
Miroslav Podhola ◽  
Karel Vondrák ◽  
Gil Chernin
Keyword(s):  
Nephrotic Syndrome ◽  
Clinical Improvement ◽  
Combined Therapy ◽  
Immunosuppressive Agents ◽  
Gene Mutations ◽  
First Year ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Heterozygous Form ◽  
First Year Of Life

Podocin mutations (NPHS2 gene) are mostly responsible for steroid-resistant nephrotic syndrome (SRNS) of childhood onset. Patients with NPHS2 gene mutations do not respond to corticoids and other immunosuppressive agents; partial remission can be rarely induced by cyclosporin A. We present a boy, where SRNS was diagnosed within first year of life. By the age of 15 years, proteinuria reached 9000 mg/24 h, cholesterolemia 15 mmol/L, albuminemia 19.6 g/L, in spite of combined therapy with cyclosporine A, methylprednisolone, enalapril and losartan. At that time a combined heterozygous form of two NPHS2 gene mutations (p.R138Q and p.V290M) was diagnosed, methylprednisolone was discontinued and patient underwent ten plasmapheresis procedures. This resulted in clinical improvement (proteinuria 3000 mg/24 h, S-cholesterol 6 mmol/L, albumin 30g/L) lasting for three years. In conclusion, plasmapheresis can result in clinical improvement and stabilization of SRNS caused by podocine mutation, before renal replacement therapy is initiated.

scholarly journals Wilms′ tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome

2016 ◽  
Vol 144 (2) ◽  
pp. 276 ◽  
Author(s):  
Prabha Senguttuvan ◽  
AravindSelvin Kumar ◽  
R Srilakshmi ◽  
SMK Karthickeyan ◽  
K Balakrishnan ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Gene Mutations ◽  
Wilms Tumour ◽  
Indian Children ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
South Indian

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.

Sign in / Sign up

Export Citation Format

Share Document