Comparison of oral and intravenous cyclophosphamide in children with steroid-resistant nephrotic syndrome

Background There are variations in remission rates following treatment of steroid-resistant nephrotic syndrome (SRNS) with cyclophosphamide.Objective To compare the efficacy of oral versus intravenous cyclophosphamide (CPA) in the management of pediatric SRNS.Methods This was a prospective study of 41 children with SRNS treated with CPA. One group received oral CPA at a dose of 2 mg/kg body weight/day for 8-12 weeks, while the other group received intravenous CPA at a dose of 500mg/m2 body surface area (BSA) monthly for 6 months. All patients were concomitantly treated with prednisone on alternate days. The primary outcome was the number of patients attaining remission.Results The study was comprised of 20 children receiving oral CPA and 21 children receiving intravenous CPA. There were 29 boys and 12 girls. The mean age of children at the onset of nephrotic syndrome (NS) was 47 ± 40 months old (range 12 months – 13 years), and the mean duration of NS before initiation of CPA therapy was 15 ± 28 months (range 1 – 129 months). Remission was achieved in 29 (70.7%) patients, with no difference between oral and intravenous route of CPA administration. The mean time to achieve remission was 22.7 weeks (about 5 months). The oral route group required less time in achieving remission than the intravenous route group. No association was found between remission and other factors, such as onset of steroid resistance, route of CPA, hypertension and hematuria. Side-effects included infection, anemia, nausea/vomiting, and alopecia. None of the patients required discontinuation of the medication.Conclusion Oral CPA was as effective as intravenous CPA for children with steroid-resistant nephrotic syndrome. [Paediatr Indones. 2011;51:266-71].

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

Immunopathologia Persa ◽

10.15171/ipp.2019.15 ◽

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.

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Intravenous cyclophosphamide in steroid-resistant nephrotic syndrome

Pediatric Nephrology ◽

10.1007/s00467-003-1095-3 ◽

2003 ◽

Vol 18 (4) ◽

pp. 351-356 ◽

Cited By ~ 29

Author(s):

Anurag Bajpai ◽

Arvind Bagga ◽

Pankaj Hari ◽

Amit Dinda ◽

Rajendra N. Srivastava

Keyword(s):

Nephrotic Syndrome ◽

Intravenous Cyclophosphamide ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome

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A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01165-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jian Li ◽

Mingyi Zhao ◽

Xinying Xiang ◽

Qingnan He ◽

Rong Gui

Keyword(s):

Nephrotic Syndrome ◽

Glycyrrhizic Acid ◽

Immune Escape ◽

Platelet Membrane ◽

Steroid Resistance ◽

Inflammatory Factors ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Anti Inflammatory

AbstractClinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core–shell structure was designed. Metal–organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS. Graphical Abstract

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The podocin V260E mutation predicts steroid resistant nephrotic syndrome in black South African children with focal segmental glomerulosclerosis

Communications Biology ◽

10.1038/s42003-019-0658-1 ◽

2019 ◽

Vol 2 (1) ◽

Cited By ~ 1

Author(s):

Melanie A. Govender ◽

June Fabian ◽

Errol Gottlich ◽

Cecil Levy ◽

Glenda Moonsamy ◽

...

Keyword(s):

Nephrotic Syndrome ◽

South African ◽

Focal Segmental Glomerulosclerosis ◽

Steroid Resistance ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Black South African ◽

African Children ◽

Segmental Glomerulosclerosis ◽

South African Children

AbstractIn black African children with focal segmental glomerulosclerosis (FSGS) there are high rates of steroid resistance. The aim was to determine genetic associations with apolipoprotein L1 (APOL1) renal risk variants and podocin (NPHS2) variants in 30 unrelated black South African children with FSGS. Three APOL1 variants were genotyped and the exons of the NPHS2 gene sequenced in the cases and controls. APOL1 risk alleles show a modest association with steroid sensitive nephrotic syndrome (SSNS) and steroid resistant nephrotic syndrome (SRNS). The NPHS2 V260E variant was present in SRNS cases (V/V = 5; V/E = 4; E/E = 11), and was absent in SSNS cases. Haplotype analysis suggests a single mutation origin for V260E and it was associated with a decline in kidney function over a 60-month period (p = 0.026). The V260E variant is a good predictor of autosomal recessive SRNS in black South African children and could provide useful information in a clinical setting.

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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

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415007850 ◽

2015 ◽

Vol 7 (1) ◽

pp. 102-107 ◽

Cited By ~ 4

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.

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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

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20202138 ◽

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.

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The importance of genetic study in steroid-resistant nephrotic syndrome

Journal of Renal Injury Prevention ◽

10.15171/jrip.2019.51 ◽

2019 ◽

Vol 8 (4) ◽

pp. 271-282 ◽

Cited By ~ 2

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.

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The Status of Oxidants and Antioxidants in Children with Nephrotic Syndrome

BioScientia Medicina ◽

10.32539/bsm.v2i1.35 ◽

2018 ◽

Vol 2 (1) ◽

pp. 24-33

Author(s):

Hertanti Indah Lestari ◽

Eka Febri Zulissetiana ◽

Ardesy Melizah

Keyword(s):

Oxidative Stress ◽

Nephrotic Syndrome ◽

Steroid Resistance ◽

Oxidative Stress Marker ◽

Steroid Resistant ◽

The Status ◽

Anti Oxidant ◽

Resistant Group ◽

The Mean ◽

The Difference

Background: The nephrotic syndrome (NS) resistance and relapse to treatment pose challenges in the management of NS. Several experimental studies on both animals and humans have assessed the association between NS and the balance between the oxidants and anti-oxidants. The study aims to compare the status of oxidants and anti-oxidants of NS patients between the massive proteinuria, the remission, the steroid resistance and the control groups. Methods: a cross-sectional design to assess the status of oxidants and antioxidants in children with the nephrotic syndrome. The eligible subjects were divided into four groups, the massive proteinuria group, the remission group, the steroid resistant group and the control group. The status of oxidants and anti-oxidant were evaluated with the Malondialdehyde (MDA) and the Total Antioxidant Status (TAS), respectively. Results: The highest mean MDA levels was observed in the steroid resistant group followed by the massive proteinuria group and the remission group. The mean MDA level of the proteinuria group (massive proteinuria and steroid-resistant) is higher than the remission group. The mean TAS levels in the remission group were higher than the massive proteinuria group, but the difference was not statistically significant. Moreover, the mean difference of SAT between the proteinuria group and without proteinuria was not statistically significant. Conclusions: The oxidative stress marker (MDA) was higher in the NS patients with proteinuria than the patients without proteinuria. The difference in the total anti-oxidant status in NS patients with massive proteinuria, remission and steroid resistance were not statistically significant. Keywords: Nephrotic syndrome, oxidative stress, anti oxidant

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