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

Northwell Health4 enrolled

Overview

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

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

Conditions

Focal Segmental Glomerulosclerosis

Interventions

Cardiovascular AssessmentOTHER

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 AssessmentOTHER

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 EvaluationOTHER

All patients will undergo genetic screening for all known podocyte gene mutations.

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 21 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Presence or Absence of any of the podocin gene mutations

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)

Time frame: baseline