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

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00883636
• Other study ID #: GCRC 0245
• Secondary ID: IRB# 08-163
• Status: Terminated
• Phase: N/A
• First received: April 17, 2009
• Last updated: June 18, 2013
• Start date: October 2008
• Est. completion date: October 2011

Study information

• Verified date: June 2013
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: October 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 21 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cardiomyopathies
• Chronic Kidney Disease
• Focal Segmental Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental
• Kidney Diseases
• Nephrosis
• Nephrotic Syndrome
• Renal Insufficiency, Chronic
• Steroid Resistant Nephrotic Syndrome
• Syndrome

Intervention

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.
• 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,
• Genetic Evaluation
All patients will undergo genetic screening for all known podocyte gene mutations.

Locations

Country	Name	City	State
United States	Schneider Children's Hospital	New Hyde Park	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence or Absence of any of the podocin gene mutations	Presence or Absence of any of the podocin gene mutations; podocin gene (NPHS2); CD2-associated protein (CD2AP); actinin-4 (ACTN4); Nephrotic syndrome steroid-resistant gene (SRN1); Wilms Tumor 1(WT1); Transient receptor potential cation channel, subfamily C, member 6 (TRPC6); Phospholipase C-E1 (PLCE-1)	baseline	No