scholarly journals Recurrent Nephrotic Plasma Activates Pro-fibrotic Signalling Pathways Downstream of Protease-activated Receptor 1

2022 ◽  
Author(s):  
Musleeha Chesor ◽  
Jack Tuffin ◽  
Carl May ◽  
Irene Ghobrial ◽  
Melissa Little ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Signalling Pathways ◽  
Fibrotic Response ◽  
Podocyte Injury ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Podocyte Loss ◽  
Protease Activated Receptor 1 ◽  
Tgf Β1 ◽  
Kidney Organoids

Abstract Recurrence of steroid-resistant nephrotic syndrome (SRNS) is thought to be due to an unknown “circulating factor”, the identity of which has so far remained elusive. Our previous work suggests a signaling role for protease-activated receptor-1 (PAR-1), leading to impaired podocyte function. Here, we show that relapse nephrotic plasma (NP), but not paired remission plasma, induced a pro-fibrotic response. This change was inhibited by PAR-1 inhibitors, but not by TGF-β1 inhibition. Four PAR-1 inhibitors demonstrated distinct antagonistic properties. The phosphorylation of VASP and JNK in a 3D spheroid model (GlomSpheres) and kidney organoids corroborated the finding from a 2D ciPods model. Functionally, relapse NP induced podocyte motility, and podocyte loss from spheroids both of which were also selectively rescued by PAR-1 inhibitors. Also, it induced the loss of podocyte-specific markers in kidney organoids. We propose that the circulating factor acts as a pro-fibrotic effector by activating PAR-1, leading to increased podocyte injury.

A rare cause of steroid-resistant nephrotic syndrome in a child: Answers

2019 ◽  
Vol 35 (4) ◽  
pp. 621-623
Author(s):  
Lale Guliyeva ◽  
Yılmaz Tabel ◽  
Ali Düzova ◽  
Nusret Akpolat ◽  
Seza Özen ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome

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

Nephron ◽  
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.

scholarly journals MP032NEXT GENERATION GENE PANEL SCREENING IN STEROID-RESISTANT NEPHROTIC SYNDROME

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i353-i353
Author(s):  
Beata S. Lipska-Ziętkiewicz ◽  
Olivia Boyer ◽  
Olivier Gribouval ◽  
Mansoureh Tabatabaei ◽  
Cecile Fourrage ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Gene Panel ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome

SP021COQ6 AND COQ2 MUTATIONS ASSOCIATED WITH STEROID RESISTANT NEPHROTIC SYNDROME

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii110-iii113
Author(s):  
Maddalena Gigante ◽  
Sterpeta Diella ◽  
Luisa Santangelo ◽  
Ottavio Amatruda ◽  
Gianluca Caridi ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome

CLINICAL CASE: STEROID-RESISTANT NEPHROTIC SYNDROME

2021 ◽  
pp. 13-17
Author(s):  
А.Е. Турсын
Keyword(s):  
Quality Of Life ◽  
Nephrotic Syndrome ◽  
Arterial Hypertension ◽  
Clinical Case ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Moderate Severity ◽  
Syndrome Diagnosis ◽  
Pathogenetic Therapy

Описан клинический случай пациент с нефротическим синдромом, стероид резистентный вариант, с артериальной гипертензией, осложненный полисерозитом (гидроторакс, асцит, плеврит). Пациент поступил в клинику в состоянии средней степени тяжести, с массивными отеками, полисерозитом, артериальной гипертензией и выраженным нефротическим синдромом. Диагноз: Гломерулярная болезнь. Нефротический синдром, стероид резистентный вариант. Функция почек снижена (СКФ- 84мл/мин по Шварцу). Двухсторонний экссудативный плеврит. Гидроторакс. Полисерозит (в рамках нефротического синдрома) был установлен на основании выраженного нефротического синдрома. Пациенту была проведена патогенетическая терапия. Отмечено улучшение состояния больного, в виде снижения отеков, нормализаций артериального давления, что в свою очередь поспособствовало сохранению и улучшению качества жизни пациента. A clinical case of a patient with nephrotic syndrome, steroidresistant variant, with arterial hypertension complicated by polyserositis (hydrothorax, ascites, pleurisy) is described. The patient was admitted to the clinic in a state of moderate severity, with massive edema, polyserositis, arterial hypertension, and severe nephrotic syndrome. Diagnosis: Glomerular disease. Nephrotic syndrome, steroidresistant variant. The kidney function is reduced (GFR - 84 ml/min according to Schwartz). Bilateral exudative pleurisy. Hydrothorax. Polyserositis (within the framework of nephrotic syndrome) was established based on the severe nephrotic syndrome. The patient underwent pathogenetic therapy. An improvement in the patient's condition was noted, in the form of a decrease in edema, normalization of blood pressure, which in turn contributed to the preservation and improvement of the patient's quality of life.

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.

SUCCESSFUL SURGICAL TREATMENT OF THROMBOSIS OF THE RIGHT ATRIUM IN A CHILD WITH STEROID-RESISTANT NEPHROTIC SYNDROME

2018 ◽  
Vol 13 (3) ◽  
pp. 145-146
Author(s):  
M.A. MARTAKOV ◽  
E.M. ZAJNETDINOV ◽  
V.P. PRONINA ◽  
N.V. SHESTERIKOV ◽  
V.V. SHESTERIKOVA ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Surgical Treatment ◽  
Right Atrium ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
The Right
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