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

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

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Disease; Focal Segmental Glomerulosclerosis; Nephrotic Syndrome; Steroid Resistant Nephrotic Syndrome
• Intervention / Treatment: 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
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Focal Segmental Glomerulosclerosis Patients and Non Focal Segmental Glomerulosclerosis SRNS patients

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Deborah Mensch, M.D., Northwell Health

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: April 17, 2009
• First Submitted That Met QC Criteria: April 17, 2009
• First Posted (Estimate): April 20, 2009

Study Record Updates

• Last Update Posted (Estimate): June 19, 2013
• Last Update Submitted That Met QC Criteria: June 18, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Podocyte Protein; Podocyte Mutation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Disease; Renal Insufficiency; Nephritis; Glomerulonephritis; Syndrome; Kidney Diseases; Renal Insufficiency, Chronic; Cardiomyopathies; Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Nephrosis
• Other Study ID Numbers: GCRC 0245; IRB# 08-163