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Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis

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ClinicalTrials.gov Identifier: NCT00883636
Recruitment Status : Terminated (study stopped due to lack of activity)
First Posted : April 20, 2009
Last Update Posted : June 19, 2013
Sponsor:
Information provided by (Responsible Party):
Northwell Health

Brief Summary:

The objective of this study is as follows:

  • Perform genetic analysis to define the prevalence of each of the known gene mutations in an unselected cohort of patients with focal segmental glomerulosclerosis (FSGS)
  • Perform a comprehensive assessment of cardiovascular status to determine the incidence of any cardiac abnormalities in patients with FSGS
  • Determine if patients with mutations in specific proteins are more likely to have cardiovascular abnormalities
  • Initiate long-term follow up in all patients to determine whether cardiac prognosis is related to any specific genetic abnormality

Condition or disease Intervention/treatment
Focal Segmental Glomerulosclerosis Nephrotic Syndrome Steroid Resistant Nephrotic Syndrome Chronic Kidney Disease Other: Cardiovascular Assessment Other: Renal Assessment Other: Genetic Evaluation

Detailed Description:

Nephrotic Syndrome is a frequent cause of chronic kidney disease in children. Patients who are unresponsive to treatment with corticosteroids are further categorized as having steroid resistant nephrotic syndrome (SRNS). Renal biopsy in SRNS patients often reveal the histological lesion of focal segmental glomerulosclerosis (FSGS).

Genetic research has identified mutations in specific podocyte proteins, which may lead to the development of steroid resistant nephrotic syndrome. In addition to being expressed in the fetal adult kidney, human podocin mRNA is also expressed in the fetal heart tissue. Multiple case reports have described an association between cardiac abnormalities and familial FSGS. These findings suggest that this gene may be involved in the pathogenesis of cardiac abnormalities seen in this population.

The objectives of this study is to:

  • Perform genetic analysis to define the prevalence of each of the known podocyte gene mutations in an unselected cohort of patients with FSGS
  • Perform a comprehensive assessment of cardiovascular status to determine the incidence of any cardiac abnormalities in patients with FSGS
  • Determine if patients with mutations in specific podocyte proteins are more likely to have cardiovascular abnormalities
  • Initiate long-term follow up in all patients to determine whether cardiac prognosis is related to any specific genetic abnormality

Study Type : Observational
Actual Enrollment : 4 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis
Study Start Date : October 2008
Primary Completion Date : August 2011
Study Completion Date : October 2011


Group/Cohort Intervention/treatment
Focal Segmental Glomerulosclerosis Other: Cardiovascular Assessment
Measure of BNP, and Pro-BNP Complete 2 Dimensional Echocardiogram with Doppler evaluation including determination of, Left Ventricular mass, Ejection fraction, Midwall fractional shortening, velocity of early and late diastolic transmitral flow, and measurement of E/A ratio, Ratio of end-systolic wall stress to rate corrected velocity of circumferential fiber shortening.
Other: Renal Assessment
Complete a metabolic panel, CMP. Calculation of glomerular filtration rate, GFR, measure of urinary total protein, albumin and creatinine excretion in a first morning urine sample, 24 hour blood pressure monitoring,
Other: Genetic Evaluation
All patients will undergo genetic screening for all known podocyte gene mutations.
Non-Focal Segmental Glomerulosclerosis Other: Cardiovascular Assessment
Measure of BNP, and Pro-BNP Complete 2 Dimensional Echocardiogram with Doppler evaluation including determination of, Left Ventricular mass, Ejection fraction, Midwall fractional shortening, velocity of early and late diastolic transmitral flow, and measurement of E/A ratio, Ratio of end-systolic wall stress to rate corrected velocity of circumferential fiber shortening.
Other: Renal Assessment
Complete a metabolic panel, CMP. Calculation of glomerular filtration rate, GFR, measure of urinary total protein, albumin and creatinine excretion in a first morning urine sample, 24 hour blood pressure monitoring,
Other: Genetic Evaluation
All patients will undergo genetic screening for all known podocyte gene mutations.



Primary Outcome Measures :
  1. Presence or Absence of any of the podocin gene mutations [ Time Frame: baseline ]

    Presence or Absence of any of the podocin gene mutations

    1. podocin gene (NPHS2)
    2. CD2-associated protein (CD2AP)
    3. actinin-4 (ACTN4)
    4. Nephrotic syndrome steroid-resistant gene (SRN1)
    5. Wilms Tumor 1(WT1)
    6. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6)
    7. Phospholipase C-E1 (PLCE-1)


Biospecimen Retention:   Samples With DNA
Blood Serum, plasma


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Ages Eligible for Study:   6 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Focal Segmental Glomerulosclerosis Patients and Non Focal Segmental Glomerulosclerosis SRNS patients
Criteria

Inclusion Criteria:

  • Age 6 months - 21 years
  • SRNS, defined as failure to achieve remission in proteinuria after 4-6 weeks of daily steroid therapy in accord with ISKDC guidelines
  • GFR > 30 ml/min/1.73 m^2
  • Renal disease diagnosed based on kidney biopsy

Exclusion Criteria:

  • Secondary FSGS
  • Prior renal transplantation
  • Congenital extra-renal abnormalities
  • Significant structural cardiac abnormalities
  • pulmonary, hematologic, malignancy, or immune-related disease
  • inability to maintain adequate follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00883636


Locations
United States, New York
Schneider Children's Hospital
New Hyde Park, New York, United States, 11040
Sponsors and Collaborators
Northwell Health
Investigators
Principal Investigator: Deborah Mensch, M.D. Northwell Health

Responsible Party: Northwell Health
ClinicalTrials.gov Identifier: NCT00883636     History of Changes
Other Study ID Numbers: GCRC 0245
IRB# 08-163
First Posted: April 20, 2009    Key Record Dates
Last Update Posted: June 19, 2013
Last Verified: June 2013

Keywords provided by Northwell Health:
Podocyte Protein
Podocyte Mutation

Additional relevant MeSH terms:
Syndrome
Kidney Diseases
Renal Insufficiency, Chronic
Cardiomyopathies
Nephrotic Syndrome
Nephrosis
Glomerulosclerosis, Focal Segmental
Disease
Pathologic Processes
Urologic Diseases
Renal Insufficiency
Heart Diseases
Cardiovascular Diseases
Glomerulonephritis
Nephritis