Nephrotic Syndrome Study Network

Study ID
STU 112012-082

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Children’s Medical Center (Dallas, Plano, Southlake)
  • Parkland Health & Hospital System

Contact
Natalie Johnson
214/645-8263
natalie.johnson@utsouthwestern.edu

Principal Investigator
Kamalanathan Sambandam

Summary

This is not a treatment study. This is a two-armed multi-center incident, observational cohort panel: Th two study arms are: Cohort a, a biopsy
group composed of two main cohorts and Cohort B, a treatment-naive, non-biopsy group of children. in the Cohort a (biopsy group)

a recruit-to-replace strategy will be utilized to ensure that the a minimum sample size of 450 participants with FSGS, MCD
and Mn and 36 months of observation each participant will have 9-10 study visits depending on date of enrollment and subsequent chart review post study timeline and/or annual visits.

This study involves a screening and baseline visit and additional followup visits after the standard of care kidney biopsy. Participants will be screened with a medical history and physical examination, as well as blood and urine samples and collection of fingernail clippings. Participants will also complete questionnaires about their history of kidney problems. During the kidney biopsy, performed at the niH Clinical Center, researchers will take an additional tissue sample for research. Participants will return for followup visits at niH every 4 months in the first year, and every 6 months in the second through fifth years after the biopsy. additional blood and urine samples will be collected at each visit, and fingernail clippings will also be collected annually by the study researchers. Treatment for kidney disease will not be provided as part of this protocol and instead will generally be provided by the patient's own physician.

The primary outcome variables are: 1)event rate change in urinary proteinuria excretion(remission, partials remission and non-remission) 2) Rate of change in renal function: 25mls/min/1.73m2 reduction in follow up estimated GFR compared to baseline GFR, 50% decline in follow up estimated GFR compared to baseline measurement and end stage renal disease.

The secondary outcome variables for the nePTune main study cohort are: 1)Patient reproted outcomes will be assessed using medication adherence and Patient Reported outcome Measurement information System (PRoMiS) questionnaires. 2) new onset Diabetes. 3) Malignancies of the skin, hematopoietic, or solid organ cancers after enrollment. 4) infectious, seroius and systemic infections of the skin or subcutaneous tissue, vascular system, peritoneum, or vital organs requiring antibiotics ( iV or oral) for [Greater Than]/[?]72 hours. 5) Thromboembolic events: renal and deep vein thrombosis, pulmonary embolus and embolic cerebrovascular accident.60 Hospitalization hours or eR/ observation unit visit [Greater Than]/[?] 24 . 7) acute Kidney injury 8) Death.

Cohort B, the treatment-naive, non-biopsy group, will consist of a minimum of 120 children with incident nephrotic syndrome (nS). enrolled over 30 months with a minimum follow-up of 36 months. a recruit-to-replace strategy will be followed to enroll up to 400 cnePTune Cohort B children to enure a minimum sample size of 120 actively followed subjects is preserved at 100% at the end of the enrollment.

The uTSW site will divide the enrollment for a combined total of 300 subjects between the main neptune study( 200 subjects) and the two new children's cohorts(50 biopsy and 50 nephrotic syndrome)

Participant Eligibility

Inclusion Criteria for the FSGS/MCD Cohort A: FSGS/MCD and MN Cohorts:

* A new diagnosis of FSGS or MCD or MN according to characteristic light, electron (EM), and immunofluorescence microscopy (IM), with presence of at least five glomeruli per biopsy available for analysis. Biopsy slides will be
reviewed and diagnosis confirmed by 2 study pathologists according to standardized criteria developed by the pathology committee (see Appendices C and D);

* Documented urinary protein excretion >=1500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit. Alternatively, an albuminuria equivalency
determined by the local site PI;

* < 80 years of age

* Completion of V1 (baseline visit) within 45 days of VBX (biopsy visit)

* Informed Consent.

Cohort B, cNEPTUNE:
criteria:

* <30 days of treatment for nephrotic syndrome

* Proteinuria/Nephrotic defined as:
o Urinalysis with >2+ protein AND edema OR
o Urinalysis with >2+ protein AND serum albumin < 3 OR
o Urine protein:creatinine ratio >2 AND serum albumin <3

* Age <19 years

* Informed Consent and Assent when applicable

Cohort B: cNEPTUNE
End Stage Kidney Disease (ESKD) defined as the need for chronic dialysis
or kidney transplant

* Prior solid organ or bone marrow transplant

* Secondary NS (systemic lupus erythematosus (SLE), vasculitis, Henoch
Schonlein Purpura, Hepatitis B, C or HIV nephropathy)

* Clinical or histological evidence of other renal diseases (Alport syndrome,
Nail Patella syndrome, Diabetic Nephropathy, monoclonal gammopathy
(multiple myelomas), genito-urinary malformations with vesico-uretheral
reflux or renal dysplasia)

* Known systemic disease diagnosis at time of enrollment with life expectancy less than 6 months

* Unwillingness or inability to give a comprehensive informed consent

* Unwillingness to comply with study procedures and visit schedule

* Institutionalized individuals (e.g., prisoners)