scholarly journals Therapies for Glomerular Diseases in Children

2018 ◽  
Vol 54 (01) ◽  
pp. 043-053
Author(s):  
Arvind Bagga
Keyword(s):  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Steroid Resistance ◽  
Glomerular Diseases ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Dependence ◽  
Frequent Relapses ◽  
Steroid Sensitive

AbstractNephrotic syndrome is an important chronic disease of childhood, with a steroid sensitive course in most patients. Research on pathogenesis has emphasized the importance of T-lymphocyte dysregulation and vascular permeability factors that alter podocyte function and glomerular permselectivity. Mutations in genes that encode important podocyte proteins and therapeutic targets within podocytes have been identified. A hypothesis unifying available evidence on pathogenesis is yet to be proposed. An important proportion of patients have difficult disease course, characterized by frequent relapses, steroid dependence or steroid resistance, requiring therapy with alternative immunosuppressive agents. Clinical studies support the use of levamisole, cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNIs) and rituximab in patients with frequent relapses or steroid dependence. The management of steroid-resistant nephrotic syndrome is difficult and patients failing to achieve remission show progressive renal damage. Prospective studies in patients with steroid sensitive and steroid resistant nephrotic syndrome are the basis of current guidelines while ongoing studies will help identify and formulate effective and safe therapies.

A genetic study of steroid-resistant nephrotic syndrome: relationship between polymorphism -173 G to C in the MIF gene and serum level MIF in children

2015 ◽  
Vol 7 (1) ◽  
pp. 102-107 ◽  
Author(s):  
O. R. Ramayani ◽  
N. Sekarwana ◽  
P. P. Trihono ◽  
A. H. Sadewa ◽  
A. Lelo
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Single Nucleotide ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Increased Risk ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

There is no satisfactory explanation as to why some nephrotic syndrome (NS) patients respond to glucocorticoids and others do not. The aim of this study was to investigate an association between single nucleotide polymorphism of the MIF gene -rs755622 and serum MIF concentrations in NS patients. During a period between November 2011 and September 2012, 120 consecutive children divided into three groups [healthy children, steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS)] were examined. Children were defined as healthy when they had a normal estimated glomerular filtration rate and spot urinary albumin creatinine ratio <150 μg/mg creatinine. SRNS was diagnosed in children who did not respond to the usual doses of steroids within 4 weeks of initiating treatment. SSNS patients were defined as those who had remission after usual doses of steroids. The genotype of -173 G to C polymorphism of the MIF gene was determined using polymerase chain reaction restriction fragment length polymorphism methods. Serum MIF concentration was measured using sandwich enzyme-linked immunosorbent assay. The allele frequency of the C allele was higher in SRNS compared with that of SSNS patients (P=0.025). There was a trend toward an association between genotypes and serum MIF disturbances. In conclusion, this study noted elevated circulating serum MIF levels and higher frequency of the C allele of the MIF gene in SRNS patients. The presence of the C allele implies an increased risk for steroid resistance.

scholarly journals Comparison of clinical and lab profile between steroid sensitive and steroid resistant nephrotic syndrome at onset of disease and evaluating predictors for developing steroid resistance in nephrotic syndrome

2020 ◽  
Vol 7 (6) ◽  
pp. 1304
Author(s):  
Anitha Palaniyandi ◽  
Subramani Palaniyandi
Keyword(s):  
Nephrotic Syndrome ◽  
Age At Onset ◽  
Steroid Resistance ◽  
First Episode ◽  
Observation Study ◽  
Serum Triglycerides ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Background: Nephrotic syndrome is a notable chronic disease in children. The objective of this study was to compare the clinical and lab profile between steroid sensitive nephrotic syndrome and steroid resistant nephrotic syndrome at the onset of disease. Certain parameters were tested if they could be significate predictors of developing steroid resistance at the onset of first episode of nephrotic syndrome.Methods: Retrospective observation study done children 1-12 years diagnosed with nephrotic syndrome in Sri Ramachandra Medical College and Hospital, Department of Paediatrics, Chennai. Sample size 150. Period of study Jan 2013- Dec 2015. Variables considered were age at onset, sex, parental consanguinity with essential lab parameters done at the onset of nephrotic syndrome proteinuria, pyuria, microscopic hematuria, urine protein creatinine ratio, serum creatinine, serum triglycerides and serum albumin. Children less than 1 year of age, cases with secondary causes of nephrotic syndrome and steroid dependant nephrotic syndrome, children with incomplete records were not included in this study. 150 cases who fulfilled the study criteria were included in this study.Results: 75 cases of steroid sensitive nephrotic syndrome (SSNS) were compared with an equal number of steroid resistant nephrotic syndrome (SRNS). 85 children had onset of disease before 3 years of age and majority had 3+ proteinuria and males predominated in both the groups. The overall consanguinity rates were higher among SRNS group. Triglyceride level >300 mg/dl predominated in SRNS group along with a higher severity of hypoalbuminemia when compared to SSNS group. None of the parameters tested were significant predictors of developing SRNS subsequently.Conclusions: Comparing steroid sensitive with steroid resistance nephrotic syndrome, no lab parameter could identify the risk of a child developing steroid resistance subsequently. This could be a field of interest in future studies that could predict the development of steroid resistance at the onset of first episode of nephrotic syndrome itself. 

scholarly journals Molecular factors predicting steroid resistance in pediatric nephrotic syndrome

2021 ◽  
pp. 32-37
Author(s):  
Ie. A. Burlaka ◽  
I. V. Bagdasarova
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Control Group ◽  
Activation Markers ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Cellular Hypoxia ◽  
Steroid Sensitive ◽  
Nephrotic Children

Objectives: the objective of this paper was to study the levels of cellular hypoxia, apoptosis controlling factors in children with steroid-sensitive and steroid-resistant nephrotic syndrome. Background: patients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. The search of the biochemical markers undergoing the steroid-resistance is under urgent need. Methods: an examination of kidney biopsies and blood of 56 patients (aged 10 to 15 years) with nephrotic syndrome was done. Conventional clinical investigations, immunohistochemistry, immunoblotting were used in this study. Results: patients with steroid-resistant nephrotic syndrome show an increased level of HIF-1 alfa (a marker of cellular hypoxia) as compared to the control group and children with steroid-sensitive nephrotic syndrome. Patients with steroid-resistant nephrotic syndrome show a down-regulation of anti-apoptotic marker BcL-xL as compared to the control group and children with steroid-sensitive nephrotic syndrome. Conclusion: hypoxia-induces disorders and apoptosis activation markers are considered to be included in the complex scheme predicting steroid-resistance in nephrotic children. 

scholarly journals The benefit of plasma exchange in anuric patient with steroid-resistant nephrotic syndrome - long-term follow-up

2004 ◽  
Vol 132 (suppl. 1) ◽  
pp. 101-105
Author(s):  
Amira Peco-Antic ◽  
Olivera Marsenic ◽  
Divna Kruscic ◽  
Mirjana Kostic ◽  
Ema Golubovic
Keyword(s):  
Nephrotic Syndrome ◽  
Plasma Exchange ◽  
Good Reason ◽  
Hypovolemic Shock ◽  
Fresh Frozen Plasma ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Frequent Relapses ◽  
Steroid Sensitive

Recently, plasma exchange (PE) has been added to the treatment regimen for patients with steroid-, cyclophosphamide-, and cyclosporine-resistant nephrotic syndrome. This is a case report of a female patient with severe acute renal failure (ARF) during the relapse of steroid-resistant nephrotic syndrome (SRNS) who recovered completely after PE and became steroid-sensitive in further follow-up of 48 months. An 8-year-old girl was referred to Nephrology Department of the University Children?s Hospital due to relapse of SRNS complicated with ARF. Her nephrotic syndrome (mesangioproliferative glomerulonephritis) was diagnosed at the age of 17 months. During the following 6 years, she was given several therapeutic regimens including pulse prednisolone, cyclophosphamide, Cyclosporine (CyA), but she continued to have frequent relapses and during the last six months she was steroid- and cyclosporine-resistant. Three days before admission, she was febrile, had cellulites of the lower abdominal wall, diarrhea, vomiting, hypovolemic shock with generalized edema, severe hypoproteinemia and hypoalbuminemia. In a local hospital, she was treated with fresh frozen plasma, albumin, methylprednisolone, furosemide and antibiotics, but she became anuric and was referred to our hospital. There were no signs of hemolysis. Anuria lasted for 12 days. She was discharged after 42 days in remission with normal GFR. Principal treatment included: 13 sequential hemodialysis sessions (30% of body weight was removed as excess volume), 6 PE, corticosteroids, CyA, ACE inhibitor, antibiotics, antimycotics, and cimetidine. Six PE sessions were performed every other day. In further 48-month follow-up, while under the treatment of CyA the patient had a few steroid-sensitive relapses, the first being 6 months after PE. The second kidney biopsy showed focal segmental glomerulosclerosis with no signs of apparent CyA nephrotoxicity. ?Malignant? course of disease in our patient was a good reason to introduce PE into the treatment. Since PE was the only additional mode of treatment, it is believed that its effect was crucial for milder activity of the disease.

MO1027EFFICACY OF CALCINEURIN INHIBITORS IN CHILDREN WITH MONOGENIC STEROID-RESISTANT NEPHROTIC SYNDROME

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Larisa Prikhodina ◽  
Svetlana Papizh ◽  
Inna Povolotskaya
Keyword(s):  
Nephrotic Syndrome ◽  
Calcineurin Inhibitors ◽  
Compound Heterozygous ◽  
Target Level ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Pathogenic Variants ◽  
Nail Patella Syndrome

Abstract Background and Aims Monogenic causes of steroid-resistant nephrotic syndrome (SRNS) have been reported for up to one-third of children depending on age of the disease onset. Immunosuppressive treatment of genetic SRNS with calcineurin inhibitors (CNIs) is still controversial. The aim of the study was to investigate the efficacy of CNIs with focus on inducing remission and long-term kidney function in children with monogenic SRNS. Method Retrospective analysis of efficacy CNIs in five children (2M/3F) with monogenic SRNS was performed. Kidney biopsy prior CNIs revealed FSGS (n=4) and MCD (n=1). The initial cyclosporine (CsA) dose was 5 mg/kg/24h to keep a target level of 80-150 ng/ml and tacrolimus (TAC) - 0.1 mg/kg/24h to achieve a target level of 5-10 ng/ml. CsA took all 5 patients with subsequent switching to TAC in 2 children due to cosmetic side effects. The median follow-up period was 165.0 (IQR: 59.0; 185.5) months. Next generation sequencing (NGS) was used for identification of pathogenic variants in all patients. Results The median age at onset of monogenic SRNS was 33.0 (IQR: 16.5; 63.0) months. 2/5 (40%) patients presented with acute SRNS, 1/5 (20%) child with infantile NS, 1/5 (20%) - with isolated nephrotic range proteinuria with hypoalbuminemia and 1/5 (20%) - with NS and extrarenal features of Nail-Patella syndrome. NGS identified previously described pathogenic variants in all 5 children, including NPHS2 homozygous c.28dup (p.Glu87Ter) (n=1), NPHS2 compound heterozygous c.868G&gt;A (p.Val290Met) in combination with c.686G&gt;A (p.Arg229Gln) (n=1), LMX1B heterozygous c.788T&gt;G (p.Val263Gly) (n=1), LMX1B heterozygous c.737G&gt;A (p.Arg246Gln) (n=1), and COL4A3 heterozygous c.2962G&gt;A (p.Gly988Arg) variant (n=1). The median time from diagnosis to initiation of CNIs treatment was 72.0 (IQR: 33.0; 93.0) months. CNIs induced complete remission in 2/5 (40%) patients, presented with acute SRNS, including one girl with MCD due to NPHS2 compound heterozygous variants with mutation-dependent pathogenicity of one (p.R229Q) of them and one boy with FSGS due to COL4A3 heterozygous variant (n=1). Partial remission was induced by CNIs in 2/5 (40%) girls with FSGS due to LMX1B heterozygous variants with isolated SRNS (n=1) and Nail-Patella syndrome (n=1). The median duration of CNIs treatment to obtain complete or partial remission was 13.5 (IQR: 6.8; 15.8) months. Acute CNIs-associated nephrotoxicity had 2 patients with LMX1B variants. At the last follow up full and partial responders to CNIs treatment aged of 16.5 (IQR: 11.8; 17.5) years had CKD-1 (n=3) and CKD-2 (n=1). 1/5 (20%) boy with NPHS2-associated infantile NS was CNI resistant and developed CKD-5 at the age of 6.5 years with subsequent living related kidney transplantation. Conclusion We found that 4/5 (80%) children with monogenic SRNS demonstrated partial or full response to CNIs treatment with stable long-term kidney function. We assume that CNIs might improve podocyte function by stabilization of their cytoskeleton disrupted in patients with monogenic SRNS.

scholarly journals Reverse Phenotyping after Whole-Exome Sequencing in Steroid-Resistant Nephrotic Syndrome

2019 ◽  
Vol 15 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Samuela Landini ◽  
Benedetta Mazzinghi ◽  
Francesca Becherucci ◽  
Marco Allinovi ◽  
Aldesia Provenzano ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Signs ◽  
Long Term Outcome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Steroid Sensitive

Background and objectivesNephrotic syndrome is a typical presentation of genetic podocytopathies but occasionally other genetic nephropathies can present as clinically indistinguishable phenocopies. We hypothesized that extended genetic testing followed by reverse phenotyping would increase the diagnostic rate for these patients.Design, setting, participants, & measurementsAll patients diagnosed with nephrotic syndrome and referred to our center between 2000 and 2018 were assessed in this retrospective study. When indicated, whole-exome sequencing and in silico filtering of 298 genes related to CKD were combined with subsequent reverse phenotyping in patients and families. Pathogenic variants were defined according to current guidelines of the American College of Medical Genetics.ResultsA total of 111 patients (64 steroid-resistant and 47 steroid-sensitive) were included in the study. Not a single pathogenic variant was detected in the steroid-sensitive group. Overall, 30% (19 out of 64) of steroid-resistant patients had pathogenic variants in podocytopathy genes, whereas a substantial number of variants were identified in other genes, not commonly associated with isolated nephrotic syndrome. Reverse phenotyping, on the basis of a personalized diagnostic workflow, permitted to identify previously unrecognized clinical signs of an unexpected underlying genetic nephropathy in a further 28% (18 out of 64) of patients. These patients showed similar multidrug resistance, but different long-term outcome, when compared with genetic podocytopathies.ConclusionsReverse phenotyping increased the diagnostic accuracy in patients referred with the diagnosis of steroid-resistant nephrotic syndrome.

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.

Levamisole treatment in steroid-sensitive and steroid-resistant nephrotic syndrome

1998 ◽  
Vol 12 (6) ◽  
pp. 459-462 ◽  
Author(s):  
K. Tenbrock ◽  
J. Müller-Berghaus ◽  
A. Fuchshuber ◽  
D. Michalk ◽  
U. Querfeld
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive

scholarly journals Rituximab versus cyclophosphamide for the treatment of children with steroid resistance nephrotic syndrome; a clinical trial study

2019 ◽  
Vol 5 (2) ◽  
pp. e15-e15
Author(s):  
Mohsen Akhavan Sepahi ◽  
Najmeh Farahani ◽  
Mohammad Reza Razavi ◽  
Hossein Heydari ◽  
Shahram Arsang-Jang
Keyword(s):  
Clinical Trial ◽  
Nephrotic Syndrome ◽  
Intervention Group ◽  
T Test ◽  
Steroid Resistance ◽  
Control Group ◽  
Steroid Resistant ◽  
Steroid Administration ◽  
Frequent Relapses ◽  
The Mean

Introduction: The most common complications of the nephrotic syndrome (NS) are the frequent relapses, steroid resistance, and long-term steroid administration. Objectives: This study aimed to compare the therapeutic effect of rituximab versus cyclophosphamide in the prevention of relapses and the complications of treatment in children with steroid-resistant NS. Patients and Methods: This clinical trial study was performed on 50 patients with resistant steroidal NS referred to Masoumeh hospital in Qom, Iran. Patients were randomly divided into the two groups including intervention (n=20) and control groups (n=30). In addition to the prednisolone, the intervention group received 375 mg/m2/weekly rituximab intravenously for 4 weeks. The control group received oral doses of cyclophosphamide 2 mg/kg/d for 3 months. During treatment, the frequency of relapses, the mean dose of steroid and the complications of treatment were compared with a paired t-test, independent t-test, and chi-square test. Results: A significant decrease in the mean dose of steroids and the mean number of relapses were seen in patients after administration of rituximab and cyclophosphamide (P<0.001). However, rituximab reduced the dose of steroid administration by 12.25 mg/d, while cyclophosphamide reduced only 2.83 mg/d (P<0.001). Rituximab reduced the relapse rate two times on average, while cyclophosphamide reduced only 0.5 times (P<0.001). The incidence of complications in the cyclophosphamide group was found to be more severe than the rituximab group. Conclusion: To compare rituximab versus cyclophosphamide regarding lower the frequency of recurrence after treatment, we found rituximab is a more suitable drug for the treatment of steroid-resistant NS than cyclophosphamide.

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.

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