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

Study Overview
=================
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

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

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

Conditions
-----------------
Focal Segmental Glomerulosclerosis, Nephrotic Syndrome, Steroid Resistant Nephrotic Syndrome, Chronic Kidney Disease

Intervention / Treatment
-----------------
* Other: Cardiovascular Assessment
* Other: Renal Assessment
* Other: Genetic Evaluation


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Focal Segmental Glomerulosclerosis<br> | Other: Cardiovascular Assessment<br>* 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.<br>Other: Renal Assessment<br>* 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,<br>Other: Genetic Evaluation<br>* All patients will undergo genetic screening for all known podocyte gene mutations.<br>|
| Non-Focal Segmental Glomerulosclerosis<br> | Other: Cardiovascular Assessment<br>* 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.<br>Other: Renal Assessment<br>* 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,<br>Other: Genetic Evaluation<br>* All patients will undergo genetic screening for all known podocyte gene mutations.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Podocyte Protein, Podocyte Mutation