Nephrotic SyndromeNCT03326037
Study of The Association of Mutations in The NPHS2 Gene and Nephrotic Syndrome in Children and Adults in Middle East
An observational study of Nephrotic Syndrome, run by AHMED ABDULQADER HAMMOUDA ABOU SHALL at 1 site in Kuwait.
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. Read more about this study
- Who is it for?
- Ages 2 to 50 years
- Conditions the study is for
- Nephrotic Syndrome
- What is being tested?
- Genotyping of the NPHS2 variant rs61747728
- How many people
- 150 participants
- Where
- 1 siteKuwait
- Study dates
- Oct 2016to Jun 2020
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: 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
Who may be able to join
- Inclusions criteria in children:
- All children who presented with acute onset of heavy proteinuria (>3 g/24hrs).
- If a biopsy was performed then only a diagnosis of MCD or FSGS will be included after performing light microscopy, immunofluorescence or immunoperoxidase testing and electron microscopy. These studies will be reviewed by the primary investigator.
- If a biopsy is not performed as is the case with many children, then the clinical and serological parameters should be consistent with MCD or FSGS as evidenced by the negativity of autoimmune and infectious markers.. The cut off age used in referring patients to adult nephrologists is 16 years.
- Inclusions criteria in adults :
- All patients with proteinuria of acute or gradual onset but has to be more than 1g/24hrs. A biopsy must have been performed and reviewed by the primary investigator and the results should be MCD/FSGS after applying all the aforementioned pathological studies.
Who cannot join
- 1) All patients diagnosed as MCD secondary to:-
- Drugs:NSAIDs (most common), antimicrobials, lithium, bisphosphonates, and penicillamine (many others).
- Cancer:haematological malignancies (most common), solid organ malignancies (rarely associated with MCD).
- Infections:(rarely):esp.TB,syphilis,HIV, HCV, mycoplasma.
- Atopy:30% of MCD patients.
- Immunizations.
Show all 13Show fewer
- 2) All patients diagnosed as FSGS secondary to:-
- <!-- -->
- Infection (podocyte invasion): HIV-associated nephropathy (HIVAN) , Parvovirus B19.
- Drugs (podocyte toxicity): Pmidronate, lithium, interferon, and heroin.
- Congenital or acquired nephron mass reduction: Renal dyplasia, reflux nephropathy, renovascular disease, partial or unilateral nephrectomy.
- Hyperfiltration as part of disease process: Morbid obesity, diabetic nephropathy, pre-eclampsia, sickle cell disease.
- Any cause of glomerular disease with progressive scarring: Eg. Membranous GN, IgAN, Alport syndrome, thrombotic microangiopathy, vasculitis.
Trial locations and contacts
1 site in 1 country.
About this study
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 .
Read more
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:-
- Understanding the biology of the disease in this part of the world.
- Counselling patients about their clinical course and what medication they will respond to.
- Counselling patients about the possibility of a kidney transplant sooner in their disease course
Read the detailed description
Aim of the work:
The aim of this study is:
- To identify any relationship between NPHS2 gene mutations and NS in children and adults in Middle East.
- 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.
- To compare our results with similar data from other World populations/ethnic groups.
- 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.
- Conditions
- Nephrotic Syndrome
- Being tested
- Genotyping of the NPHS2 variant rs61747728
- Keywords
- Nephrotic Syndrome, NPHS2 gene mutation, disease association
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genotyping of the NPHS2 variant rs61747728Genetic
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)
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants achieving NPHS2 gene mutations (frequency of p.R229Q polymorphic site) in patients with steroid-resistant nephrotic syndrome in comparison with steroid - sensitive nephrotic syndrome
participants will be monitored for up to 2 years and classified as steroid -sensitive nephrotic syndrome or steroid - resistant nephrotic syndrome according to clinical response to steroid therapy ( 1 mg prednisolone /kg) for total 6 weeks.
Renal biopsy will be done for all patients above 5 years of age (MCD and FSGS) were included.
Blood sample or buccal swab will be collected from all patients and genotyping of the NPHS2 gene variant will be performed to report number of participants with NPHS2 gene mutations to share our results with the treating clinicians so that counselling of the patients can be done in terms of advising for kidney transplant sooner in their clinical course, prognosis and family screening.
Measured: Baseline to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2017
- Study startOct 2016
- Primary completionOct 2019 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Nephrotic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- AHMED ABDULQADER HAMMOUDA ABOU SHALL
- Sponsor type
- University, hospital or other
- Collaborators
- Kuwait University, Assiut University
- Responsible party
- Sponsor-investigator, AHMED ABDULQADER HAMMOUDA ABOU SHALL, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03326037
- Sponsor's protocol ID
- MG03/15
- Status last verified
- Jan 2019
- First submitted
- 22 Oct 2017
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
McKenzie LM, Hendrickson SL, Briggs WA, Dart RA, Korbet SM, Mokrzycki MH, Kimmel PL, Ahuja TS, Berns JS, Simon EE, Smith MC, Trachtman H, Michel DM, Schelling JR, Cho M, Zhou YC, Binns-Roemer E, Kirk GD, Kopp JB, Winkler CA. NPHS2 variation in sporadic focal segmental glomerulosclerosis. J Am Soc Nephrol. 2007 Nov;18(11):2987-95. doi: 10.1681/ASN.2007030319. Epub 2007 Oct 17.
PubMed 17942957Pollak MR. Inherited podocytopathies: FSGS and nephrotic syndrome from a genetic viewpoint. J Am Soc Nephrol. 2002 Dec;13(12):3016-23. doi: 10.1097/01.asn.0000039569.34360.5e. No abstract available.
PubMed 12444222Buscher AK, Weber S. Educational paper: the podocytopathies. Eur J Pediatr. 2012 Aug;171(8):1151-60. doi: 10.1007/s00431-011-1668-2. Epub 2012 Jan 13.
PubMed 22237399McCarthy HJ, Bierzynska A, Wherlock M, Ognjanovic M, Kerecuk L, Hegde S, Feather S, Gilbert RD, Krischock L, Jones C, Sinha MD, Webb NJ, Christian M, Williams MM, Marks S, Koziell A, Welsh GI, Saleem MA; RADAR the UK SRNS Study Group. Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2013 Apr;8(4):637-48. doi: 10.2215/CJN.07200712. Epub 2013 Jan 24.
PubMed 23349334Franceschini N, North KE, Kopp JB, McKenzie L, Winkler C. NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med. 2006 Feb;8(2):63-75. doi: 10.1097/01.gim.0000200947.09626.1c.
PubMed 16481888Dusel JA, Burdon KP, Hicks PJ, Hawkins GA, Bowden DW, Freedman BI. Identification of podocin (NPHS2) gene mutations in African Americans with nondiabetic end-stage renal disease. Kidney Int. 2005 Jul;68(1):256-62. doi: 10.1111/j.1523-1755.2005.00400.x.
PubMed 15954915Zhang SY, Marlier A, Gribouval O, Gilbert T, Heidet L, Antignac C, Gubler MC. In vivo expression of podocyte slit diaphragm-associated proteins in nephrotic patients with NPHS2 mutation. Kidney Int. 2004 Sep;66(3):945-54. doi: 10.1111/j.1523-1755.2004.00840.x.
PubMed 15327385Rood IM, Deegens JK, Wetzels JF. Genetic causes of focal segmental glomerulosclerosis: implications for clinical practice. Nephrol Dial Transplant. 2012 Mar;27(3):882-90. doi: 10.1093/ndt/gfr771. Epub 2012 Feb 14.
PubMed 22334613Jain V, Feehally J, Jones G, Robertson L, Nair D, Vasudevan P. Steroid-resistant nephrotic syndrome with mutations in NPHS2 (podocin): report from a three-generation family. Clin Kidney J. 2014 Jun;7(3):303-5. doi: 10.1093/ckj/sfu028. Epub 2014 Apr 2.
PubMed 25852895Reiterova J, Safrankova H, Obeidova L, Stekrova J, Maixnerova D, Merta M, Tesar V. Mutational analysis of the NPHS2 gene in Czech patients with idiopathic nephrotic syndrome. Folia Biol (Praha). 2012;58(2):64-8. doi: 10.14712/fb2012058020064.
PubMed 22578956Fotouhi N, Ardalan M, Jabbarpour Bonyadi M, Abdolmohammadi R, Kamalifar A, Nasri H, Einollahi B. R229Q polymorphism of NPHS2 gene in patients with late-onset steroid-resistance nephrotic syndrome: a preliminary study. Iran J Kidney Dis. 2013 Sep;7(5):399-403.
PubMed 24072153Joshi S, Andersen R, Jespersen B, Rittig S. Genetics of steroid-resistant nephrotic syndrome: a review of mutation spectrum and suggested approach for genetic testing. Acta Paediatr. 2013 Sep;102(9):844-56. doi: 10.1111/apa.12317. Epub 2013 Jul 10.
PubMed 23772861
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of The Association of Mutations in The NPHS2 Gene and Nephrotic Syndrome in Children and Adults in Middle East
- ClinicalTrials.gov ID
- NCT03326037
- Acronym / sponsor ID
- MG03/15
- Conditions
- Nephrotic Syndrome
- Keywords
- Nephrotic Syndrome, NPHS2 gene mutation, disease association
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- AHMED ABDULQADER HAMMOUDA ABOU SHALLUniversity, hospital or other
- Collaborators
- Kuwait University, Assiut University
- Study start
- Oct 2016 (actual)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 30 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:-
- Understanding the biology of the disease in this part of the world.
- Counselling patients about their clinical course and what medication they will respond to.
- Counselling patients about the possibility of a kidney transplant sooner in their disease course
Detailed description
Aim of the work:
The aim of this study is:
- To identify any relationship between NPHS2 gene mutations and NS in children and adults in Middle East.
- 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.
- To compare our results with similar data from other World populations/ethnic groups.
- 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
Who may qualify
- Ages
- 2 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- 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
Key inclusion criteria (6 listed)
- Inclusions criteria in children:
- All children who presented with acute onset of heavy proteinuria (>3 g/24hrs).
- If a biopsy was performed then only a diagnosis of MCD or FSGS will be included after performing light microscopy, immunofluorescence or immunoperoxidase testing and electron microscopy. These studies will be reviewed by the primary investigator.
- If a biopsy is not performed as is the case with many children, then the clinical and serological parameters should be consistent with MCD or FSGS as evidenced by the negativity of autoimmune and infectious markers.. The cut off age used in referring patients to adult nephrologists is 16 years.
- All patients with proteinuria of acute or gradual onset but has to be more than 1g/24hrs. A biopsy must have been performed and reviewed by the primary investigator and the results should be MCD/FSGS after applying all the aforementioned pathological studies.
Key exclusion criteria (13 listed)
- 1) All patients diagnosed as MCD secondary to:-
- 2) All patients diagnosed as FSGS secondary to:-
- <!-- -->
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genotyping of the NPHS2 variant rs61747728Genotyping 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) | Genetic | – |
Primary outcome
Number of participants achieving NPHS2 gene mutations (frequency of p.R229Q polymorphic site) in patients with steroid-resistant nephrotic syndrome in comparison with steroid - sensitive nephrotic syndrome
Time frame: Baseline to 2 years
participants will be monitored for up to 2 years and classified as steroid -sensitive nephrotic syndrome or steroid - resistant nephrotic syndrome according to clinical response to steroid therapy ( 1 mg prednisolone /kg) for total 6 weeks. Renal biopsy will be done for all patients above 5 years of age (MCD and FSGS) were included. Blood sample or buccal swab will be collected from all patients and genotyping of the NPHS2 gene variant will be performed to report number of participants with NPHS2 gene mutations to share our results with the treating clinicians so that counselling of the patients can be done in terms of advising for kidney transplant sooner in their clinical course, prognosis and family screening.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Results publication: PubMed 17942957McKenzie LM, Hendrickson SL, Briggs WA, Dart RA, Korbet SM, Mokrzycki MH, Kimmel PL, Ahuja TS, Berns JS, Simon EE, Smith MC, Trachtman H, Michel DM, Schelling JR, Cho M, Zhou YC, Binns-Roemer E, Kirk GD, Kopp JB, Winkler CA. NPHS2 variation in sporadic focal segmental glomerulosclerosis. J Am Soc Nephrol. 2007 Nov;18(11):2987-95. doi: 10.1681/ASN.2007030319. Epub 2007 Oct 17.
- Results publication: PubMed 12444222Pollak MR. Inherited podocytopathies: FSGS and nephrotic syndrome from a genetic viewpoint. J Am Soc Nephrol. 2002 Dec;13(12):3016-23. doi: 10.1097/01.asn.0000039569.34360.5e. No abstract available.
- Results publication: PubMed 22237399Buscher AK, Weber S. Educational paper: the podocytopathies. Eur J Pediatr. 2012 Aug;171(8):1151-60. doi: 10.1007/s00431-011-1668-2. Epub 2012 Jan 13.
- Results publication: PubMed 23349334McCarthy HJ, Bierzynska A, Wherlock M, Ognjanovic M, Kerecuk L, Hegde S, Feather S, Gilbert RD, Krischock L, Jones C, Sinha MD, Webb NJ, Christian M, Williams MM, Marks S, Koziell A, Welsh GI, Saleem MA; RADAR the UK SRNS Study Group. Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2013 Apr;8(4):637-48. doi: 10.2215/CJN.07200712. Epub 2013 Jan 24.
- Results publication: PubMed 16481888Franceschini N, North KE, Kopp JB, McKenzie L, Winkler C. NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med. 2006 Feb;8(2):63-75. doi: 10.1097/01.gim.0000200947.09626.1c.
- Results publication: PubMed 15954915Dusel JA, Burdon KP, Hicks PJ, Hawkins GA, Bowden DW, Freedman BI. Identification of podocin (NPHS2) gene mutations in African Americans with nondiabetic end-stage renal disease. Kidney Int. 2005 Jul;68(1):256-62. doi: 10.1111/j.1523-1755.2005.00400.x.
- Results publication: PubMed 15327385Zhang SY, Marlier A, Gribouval O, Gilbert T, Heidet L, Antignac C, Gubler MC. In vivo expression of podocyte slit diaphragm-associated proteins in nephrotic patients with NPHS2 mutation. Kidney Int. 2004 Sep;66(3):945-54. doi: 10.1111/j.1523-1755.2004.00840.x.
- Results publication: PubMed 22334613Rood IM, Deegens JK, Wetzels JF. Genetic causes of focal segmental glomerulosclerosis: implications for clinical practice. Nephrol Dial Transplant. 2012 Mar;27(3):882-90. doi: 10.1093/ndt/gfr771. Epub 2012 Feb 14.
- Results publication: PubMed 25852895Jain V, Feehally J, Jones G, Robertson L, Nair D, Vasudevan P. Steroid-resistant nephrotic syndrome with mutations in NPHS2 (podocin): report from a three-generation family. Clin Kidney J. 2014 Jun;7(3):303-5. doi: 10.1093/ckj/sfu028. Epub 2014 Apr 2.
- Results publication: PubMed 22578956Reiterova J, Safrankova H, Obeidova L, Stekrova J, Maixnerova D, Merta M, Tesar V. Mutational analysis of the NPHS2 gene in Czech patients with idiopathic nephrotic syndrome. Folia Biol (Praha). 2012;58(2):64-8. doi: 10.14712/fb2012058020064.
- Results publication: PubMed 24072153Fotouhi N, Ardalan M, Jabbarpour Bonyadi M, Abdolmohammadi R, Kamalifar A, Nasri H, Einollahi B. R229Q polymorphism of NPHS2 gene in patients with late-onset steroid-resistance nephrotic syndrome: a preliminary study. Iran J Kidney Dis. 2013 Sep;7(5):399-403.
- Results publication: PubMed 23772861Joshi S, Andersen R, Jespersen B, Rittig S. Genetics of steroid-resistant nephrotic syndrome: a review of mutation spectrum and suggested approach for genetic testing. Acta Paediatr. 2013 Sep;102(9):844-56. doi: 10.1111/apa.12317. Epub 2013 Jul 10.
- Individual participant dataSharing planned: Undecided
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Edema, Hypervolemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Nephrotic Syndrome, run by AHMED ABDULQADER HAMMOUDA ABOU SHALL at 1 site in Kuwait.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kuwait. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants achieving NPHS2 gene mutations (frequency of p.R229Q polymorphic site) in patients with steroid-resistant nephrotic syndrome in comparison with steroid - sensitive nephrotic syndrome (time frame: Baseline to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03326037, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2019.