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

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

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>A (p.Val290Met) in combination with c.686G>A (p.Arg229Gln) (n=1), LMX1B heterozygous c.788T>G (p.Val263Gly) (n=1), LMX1B heterozygous c.737G>A (p.Arg246Gln) (n=1), and COL4A3 heterozygous c.2962G>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.

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome in children

2015 ◽  
Vol 31 (3) ◽  
pp. 425-434 ◽  
Author(s):  
Aya Inaba ◽  
Yuko Hamasaki ◽  
Kenji Ishikura ◽  
Riku Hamada ◽  
Tomoyuki Sakai ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome

Long-term outcomes after early treatment with rituximab for Japanese children with cyclosporine- and steroid-resistant nephrotic syndrome

2018 ◽  
Vol 34 (2) ◽  
pp. 353-357 ◽  
Author(s):  
Shuichiro Fujinaga ◽  
Tomohiko Nishino ◽  
Chisato Umeda ◽  
Yuji Tomii ◽  
Yoshitaka Watanabe ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Early Treatment ◽  
Long Term Outcomes ◽  
Japanese Children ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome

scholarly journals Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children

2017 ◽  
Vol 28 (10) ◽  
pp. 3055-3065 ◽  
Author(s):  
Agnes Trautmann ◽  
Sven Schnaidt ◽  
Beata S. Lipska-Ziętkiewicz ◽  
Monica Bodria ◽  
Fatih Ozaltin ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome

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

2019 ◽  
Vol 2 (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.

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

2011 ◽  
Vol 51 (5) ◽  
pp. 266
Author(s):  
Eka Laksmi Hidayati ◽  
Sudung O. Pardede ◽  
Partini P. Trihono
Keyword(s):  
Nephrotic Syndrome ◽  
Oral Route ◽  
Steroid Resistance ◽  
Intravenous Route ◽  
Intravenous Cyclophosphamide ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Number Of Patients ◽  
The Mean ◽  
A Prospective Study

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].

Steroid-resistant nephrotic syndrome: long-term evolution after sequential therapy

2007 ◽  
Vol 22 (11) ◽  
pp. 1875-1880 ◽  
Author(s):  
Antonia Peña ◽  
Juan Bravo ◽  
Marta Melgosa ◽  
Carlota Fernandez ◽  
Carmen Meseguer ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Sequential Therapy ◽  
Long Term Evolution ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Term Evolution

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. 

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