Clinical Trials Logo

Clinical Trial Summary

Nephrotic syndrome (NS) represents one of the most common diagnoses in pediatric and adult nephrology, with a prevalence of 16 per 100,000 children and 3 per 100,000 adults in Western countries.

In most cases, the pathogenesis of NS remains elusive, and the clinical phenotype of patients does not allow discrimination among different causes. Thus, children with NS are usually treated with corticosteroids before a biopsy is taken, and approximately 80% of them respond to such a treatment. According to this observation, pediatric NS has been separated into two broad categories; Steroid-Sensitive Nephrotic Syndrome (SSNS) and Steroid-Resistant Nephrotic Syndrome (SRNS). In both these categories the biopsy result is usually Minimal Change Disease (MCD) while a few may show Focal and Segmental Glomerulosclerosis (FSGS). Although children affected by SSNS have good long-term prognosis, most patients with SRNS progress to End Stage Renal Disease (ESRD) within 2-10 years of diagnosis .

In adults a biopsy diagnosis of FSGS is more common than in children and more patients will not respond to corticosteroids alone and will need additional immunosuppressant medication. About 40% will progress to ESRD within 10 years .

Currently, at least 19 genes have been clearly identified with association to SRNS harboring ~300 independent mutations, conferring a considerable genetic heterogeneity to the disorder.

Genetic testing is emerging as a useful diagnostic tool in SRNS as it has implications for clinical course, treatment response, risk for posttransplant proteinuria and prenatal diagnosis. An approach for genetic testing based on the current evidence seems cost-effective and may help in the best possible management of SRNS .

The NPHS2 gene, is located on chromosome 1 and is also known as the Podocin gene. It encodes the podocin protein. Podocin is a 383-amino acid lipid-raft-associated protein localized at the slit diaphragm, where it is required for the structural organization and regulation of the glomerular filtration barrier. Its interaction with other slit diaphragm proteins eg. nephrin, NEPH1, CD2AP and TRPC6 is important in mechanosensation signaling, podocyte survival, cell polarity, and cytoskeletal organization .

It has been reported that variants in the NPHS2 gene are associated with NS .

The commonly studied rs61747728 NPHS2 gene polymorphism also known as p.R229Q has been reported to be associated with NS and SRNS .

However others have failed to report an association , which might be due to population differences.

The rs61747728 is a non-synonymous variant found on exon 5 which is suggested to be involved in in altering the functional properties of podocin in vitro and possibly in vivo .

The investigators will therefore investigate the frequency of the p.R229Q variant in Middle East patients with NS.

Genetic analysis will have important implications in several aspects:-

1. Understanding the biology of the disease in this part of the world.

2. Counselling patients about their clinical course and what medication they will respond to.

3. Counselling patients about the possibility of a kidney transplant sooner in their disease course


Clinical Trial Description

Aim of the work:

The aim of this study is:

1. To identify any relationship between NPHS2 gene mutations and NS in children and adults in Middle East.

2. To study the relationship of mutations in this gene with the clinical presentation, clinical coarse and response to treatment in these patients and compare it with patients without mutations in this gene.

3. To compare our results with similar data from other World populations/ethnic groups.

4. To share our results with the treating clinicians so that counselling of the patients can be done in terms of treatment, prognosis and family screening.

Anticipated outcome and benefit :

With the increasing number of patients with NS in Middle East and the higher number of consanguineous marriages as compared to other societies, the investigators are sure that many gene mutations will be uncovered that may be the same as the previously reported genes or new novel genes.

In either case the investigators would have studied the genetic predisposition in our patient population and helped the nephrologists in taking appropriate treatment decisions.

The investigators expect a total of 150 patients with NS in both children and adults. About 20% will be from the pediatric population with MCD, while about 80% will be adults with predominantly FSGS.

Patient Recruitment:

This study will include patients referred to the nephrology departments in the major hospitals in Kuwait- Mubarak,Amiri,Farwaniya, Adan and Jahra Hospitals. Both children and adults of all ages.

This study will also include patients referred to the nephrology departments in Assuit university hospitals and all Upper Egypt hospitals Both children and adults of all ages,

Procedures:

Saliva and blood sampling and DNA extraction

After obtaining informed consent from parents of children and adults, 3 ml of blood will be collected from children and in the event that the patients or their parents refuse then buccal swabs will be collected from children, and 5 ml of blood will be collected from adults.All patients will be fully informed about the methods of blood sampling or buccal swabs and A written consent will be obtained from adult patients and parents of childrens. The buccal swabs will be processed to extract DNA and stored at -20 till time of genetic analysis. Peripheral blood samples will be collected in EDTA anticoagulated tubes and DNA will be extracted according to standard methods using QIAGEN DNA blood mini kit (QIAGEN) and stored at 20 till time of analysis.

Genotyping :

Genotyping of the NPHS2 variant rs61747728 will be performed by Real-time TaqMan Allelic Discrimination Assay (Life technologies, CA, USA) according to standard manufacturer protocols. Allelic discrimination analysis will be performed and analyzed using ABI 7500 Fast Real-time PCR system SDS software (Life technologies, CA, USA).

Statistical analysis

Basic statistical analysis will performed using SPSS software (version 22; SPSS Inc, Chicago, IL, USA). The genetic analysis will be performed using the SNPassoc package from R software. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03326037
Study type Observational [Patient Registry]
Source Assiut University
Contact
Status Active, not recruiting
Phase
Start date October 2016
Completion date June 2020

See also
  Status Clinical Trial Phase
Completed NCT02238418 - Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria. Phase 4
Completed NCT01895894 - Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome Phase 4
Completed NCT01411982 - Role of PACAP in Nehprotic Syndrome N/A
Recruiting NCT00308321 - Long Term Tapering or Standard Steroids for Nephrotic Syndrome Phase 4
Recruiting NCT01240564 - The Nephrotic Syndrome Study Network (NEPTUNE) N/A
Completed NCT01252901 - Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases N/A
Completed NCT01197040 - Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome Phase 3
Terminated NCT00883636 - Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis N/A
Completed NCT00035334 - Study of the Safety and Efficacy of NC-503 in Secondary (AA) Amyloidosis Phase 2/Phase 3
Terminated NCT00004466 - Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome Phase 2
Terminated NCT04558892 - Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome. Phase 2/Phase 3
Completed NCT02257697 - A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome Phase 3
Completed NCT00362531 - Tacrolimus Combined With Prednisone Treatment of Idiopathic Membranous Nephropathy and Nephrotic Syndrome Phase 2/Phase 3
Completed NCT00289328 - Glucocorticoid-induced Osteopenia in Children N/A
Recruiting NCT04759274 - Diuretic Tuner Clinical Decision Support N/A
Completed NCT00001212 - Drug Therapy in Lupus Nephropathy Phase 2
Recruiting NCT05623033 - The Predictive Value of Dynamic Changes of CD4+T Lymphocytes in Primary Nephrotic Syndrome With Infection
Completed NCT03332420 - The Efficacy of Huaiqihuang Granule in Children With Primary Nephrotic Syndrome
Not yet recruiting NCT05904197 - Effectiveness of Educational Gamified Cards About Nephrotic Syndrome N/A
Completed NCT02438982 - Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome Phase 3