Bilateral Pulmonary Embolism in a 12-Year-Old Girl with Steroid-Resistant Nephrotic Syndrome

Nephrotic syndrome is the most common glomerular disease among children. Although most cases respond to steroid therapy, approximately 10–20% of patients exhibit resistance to conventional steroid therapy and are labeled as steroid-resistant. Such patients are at risk of complications, including infection, thrombosis, and chronic kidney disease. Nephrotic syndrome is considered a thrombogenic condition. Pulmonary embolism is associated with high mortality, and early treatment is essential for the survival of patients. Here, we report the case of a 12-year-old girl with late steroid resistance who developed bilateral pulmonary embolism.

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Whole-Exome Sequencing Solved over 2-Decade Kidney Disease Enigma

Nephron ◽

10.1159/000514293 ◽

2021 ◽

pp. 1-6

Author(s):

Suramath Isaranuwatchai ◽

Ankanee Chanakul ◽

Chupong Ittiwut ◽

Chalurmpon Srichomthong ◽

Vorasuk Shotelersuk ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Kidney Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Treatment Plan ◽

Unknown Etiology ◽

Pediatric Case ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Whole Exome

Chronic kidney disease of unknown etiology (CKDu) has been a problem in renal practice as indefinite diagnosis may lead to inappropriate management. Here, we report a 54-year-old father diagnosed with CKDu at 33 years old and his 8-year-old son with steroid-resistant nephrotic syndrome. Using whole-exome sequencing, both were found to be heterozygous for c.737G>A (p.Arg246Gln) in LMX1B. The diagnosis of LMX1B-associated nephropathy has led to changes in the treatment plan with appropriate genetic counseling. The previously reported cases with this particular mutation were also reviewed. Most children with LMX1B-associated nephropathy had nonnephrotic proteinuria with normal renal function. Interestingly, our pediatric case presented with steroid-resistant nephrotic syndrome at 8 years old and progressed to ESRD requiring peritoneal dialysis at the age of 15 years. Our report emphasized the need of genetic testing in CKDu for definite diagnosis leading to precise management.

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

Pediatric Nephrology ◽

10.1007/s00467-018-4145-6 ◽

2018 ◽

Vol 34 (2) ◽

pp. 353-357 ◽

Cited By ~ 9

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

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

Paediatrica Indonesiana ◽

10.14238/pi51.5.2011.266-71 ◽

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].

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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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Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome

Pediatric Nephrology ◽

10.1007/s00467-009-1264-0 ◽

2009 ◽

Vol 24 (11) ◽

pp. 2177-2185 ◽

Cited By ~ 47

Author(s):

Yuko Hamasaki ◽

◽

Norishige Yoshikawa ◽

Shinzaburo Hattori ◽

Satoshi Sasaki ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Steroid Therapy ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome

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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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Therapies for Glomerular Diseases in Children

Annals of the National Academy of Medical Sciences (India) ◽

10.1055/s-0040-1712821 ◽

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.

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