Brief Summary
Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and Membranous nephropathy (MN), generate an enormous individual and societal financial burden, accounting for approximately 12% of prevalent end stage renal disease (ESRD) cases (2005) at an annual cost in the US of more than $3 billion. However, the clinical classification of these diseases is widely believed to be inadequate by the scientific community. Given the poor understanding of MCD/FSGS and MN biology, it is not surprising that the available therapies are imperfect. The therapies lack a clear biological basis, and as many families have experienced, they are often not beneficial, and in fact may be significantly toxic. Given these observations, it is essential that research be conducted that address these serious obstacles to effectively caring for patients.
In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium.
Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.
In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium.
Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.
Brief Title
Nephrotic Syndrome Study Network
Detailed Description
Idiopathic Nephrotic Syndrome (NS) is a rare disease syndrome responsible for approximately 12% of all causes of end-stage kidney disease (ESRD) and up to 20% of ESRD in children. Treatment strategies for Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN), the major causes of NS, include high dose prolonged steroid therapy, cyclophosphamide, cyclosporine A, tacrolimus, mycophenolate mofetil and other immunosuppressive agents, which all carry significant side effects. Failure to obtain remission using the current treatment approaches frequently results in progression to ESRD with its associated costs, morbidities, and mortality. In the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry, half of the pediatric patients with Steroid Resistant Nephrotic Syndrome required renal replacement therapy within two years of being enrolled in the disease registry. FSGS also has a high recurrence rate following kidney transplantation (30-40%) and is the most common recurrent disease leading to allograft loss.
The prevailing classification of Nephrotic Syndrome categorizes patients into FSGS, MCD, and MN, if in the absence of other underlying causes, glomerular histology shows a specific histological pattern. This classification does not adequately predict the heterogeneous natural history of patients with FSGS, MCD, and MN. Major advances in understanding the pathogenesis of FSGS and MCD have come over the last ten years from the identification of several mutated genes responsible for causing Steroid Resistant Nephrotic Syndrome (SRNS) presenting with FSGS or MCD histopathology in humans and model organisms. These functionally distinct genetic disorders can present with indistinguishable FSGS lesions on histology confirming the presence of heterogeneous pathogenic mechanisms under the current histological diagnoses.
The limited understanding of FSGS, MCD, and MN biology in humans has necessitated a descriptive classification system in which heterogeneous disorders are grouped together. This invariably consigns these heterogeneous patients to the same therapeutic approaches, which use blunt immunosuppressive drugs that lack a clear biological basis, are often not beneficial, and are complicated by significant toxicity. The foregoing shortcomings make a strong case that concerted and innovative investigational strategies combining basic science, translational, and clinical methods should be employed to study FSGS, MCD, and MN. It is for these reasons that the Nephrotic Syndrome Study Network is established to conduct clinical and translational research in patients with FSGS/MCD and MN.
The prevailing classification of Nephrotic Syndrome categorizes patients into FSGS, MCD, and MN, if in the absence of other underlying causes, glomerular histology shows a specific histological pattern. This classification does not adequately predict the heterogeneous natural history of patients with FSGS, MCD, and MN. Major advances in understanding the pathogenesis of FSGS and MCD have come over the last ten years from the identification of several mutated genes responsible for causing Steroid Resistant Nephrotic Syndrome (SRNS) presenting with FSGS or MCD histopathology in humans and model organisms. These functionally distinct genetic disorders can present with indistinguishable FSGS lesions on histology confirming the presence of heterogeneous pathogenic mechanisms under the current histological diagnoses.
The limited understanding of FSGS, MCD, and MN biology in humans has necessitated a descriptive classification system in which heterogeneous disorders are grouped together. This invariably consigns these heterogeneous patients to the same therapeutic approaches, which use blunt immunosuppressive drugs that lack a clear biological basis, are often not beneficial, and are complicated by significant toxicity. The foregoing shortcomings make a strong case that concerted and innovative investigational strategies combining basic science, translational, and clinical methods should be employed to study FSGS, MCD, and MN. It is for these reasons that the Nephrotic Syndrome Study Network is established to conduct clinical and translational research in patients with FSGS/MCD and MN.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
734-615-5021
Central Contact Email
NEPTUNE-Study@umich.edu
Central Contact Role
Contact
Central Contact Phone
734-615-5017
Central Contact Email
NEPTUNE-Study@umich.edu
Completion Date
Completion Date Type
Estimated
Conditions
Minimal Change Disease (MCD)
Membranous Nephropathy
Glomerulosclerosis, Focal Segmental
Eligibility Criteria
Cohort A (biopsy cohort) Inclusion Criteria:
Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting the following inclusion criteria:
* 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.
* Scheduled renal biopsy
Cohort B (non-biopsy, cNEPTUNE) Inclusion Criteria:
* Age \<19 years of age
* Initial presentation with \<30 days immunosuppression therapy
* Proteinuria/nephrotic
* UA\>2+ and edema OR
* UA\>2+ and serum albumin \<3 OR
* UPC \> 2g/g and serum albumin \<3
Exclusion Criteria (Cohort A\&B):
* Prior solid organ transplant
* A clinical diagnosis of glomerulopathy without diagnostic renal biopsy
* Clinical, serological or histological evidence of systemic lupus erythematosus (SLE) as defined by the ARA criteria. Patients with membranous in combination with SLE will be excluded because this entity is well defined within the International Society of Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently overlaps with other classification categories of SLE nephritis (68)
* Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-urethral reflux or renal dysplasia)
* Known systemic disease diagnosis at time of enrollment with a 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)
Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting the following inclusion criteria:
* 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.
* Scheduled renal biopsy
Cohort B (non-biopsy, cNEPTUNE) Inclusion Criteria:
* Age \<19 years of age
* Initial presentation with \<30 days immunosuppression therapy
* Proteinuria/nephrotic
* UA\>2+ and edema OR
* UA\>2+ and serum albumin \<3 OR
* UPC \> 2g/g and serum albumin \<3
Exclusion Criteria (Cohort A\&B):
* Prior solid organ transplant
* A clinical diagnosis of glomerulopathy without diagnostic renal biopsy
* Clinical, serological or histological evidence of systemic lupus erythematosus (SLE) as defined by the ARA criteria. Patients with membranous in combination with SLE will be excluded because this entity is well defined within the International Society of Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently overlaps with other classification categories of SLE nephritis (68)
* Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-urethral reflux or renal dysplasia)
* Known systemic disease diagnosis at time of enrollment with a 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)
Inclusion Criteria
Inclusion Criteria:
Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting the following inclusion criteria:
* 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.
* Scheduled renal biopsy
Cohort B (non-biopsy, cNEPTUNE) Inclusion Criteria:
* Age \<19 years of age
* Initial presentation with \<30 days immunosuppression therapy
* Proteinuria/nephrotic
* UA\>2+ and edema OR
* UA\>2+ and serum albumin \<3 OR
* UPC \> 2g/g and serum albumin \<3
Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting the following inclusion criteria:
* 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.
* Scheduled renal biopsy
Cohort B (non-biopsy, cNEPTUNE) Inclusion Criteria:
* Age \<19 years of age
* Initial presentation with \<30 days immunosuppression therapy
* Proteinuria/nephrotic
* UA\>2+ and edema OR
* UA\>2+ and serum albumin \<3 OR
* UPC \> 2g/g and serum albumin \<3
Gender
All
Gender Based
false
Keywords
Focal and Segmental Glomerulosclerosis
Focal & Segmental Glomerulosclerosis
Focal Segmental Glomerulosclerosis
FSGS
Minimal change disease
MCD
Membranous Nephropathy
MN
Nephrotic Syndrome
Neph Syndrome
NEPTUNE
NephCure
Halpin
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
NCT Id
NCT01209000
Org Class
Other
Org Full Name
University of Michigan
Org Study Id
6801
Overall Status
Recruiting
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network
Primary Outcomes
Outcome Description
Defined as remission, partial remission and non-remission
Outcome Measure
Event rate of change in urinary protein excretion and renal function.
Outcome Time Frame
60 months
Outcome Description
Defined as:
1. 25 mls/min/1.73m2 reduction in follow-up estimated GFR (using the 4-variable MDRD equation for ages ≥18 years and modified Schwartz for ages \<18 years) compared to baseline estimated GFR
2. 50% decline in follow-up estimated GFR compared to baseline measurement
3. End stage renal disease defined as estimated GFR ≤10cc/min, initiation of maintenance dialysis or preemptive kidney transplantation.
1. 25 mls/min/1.73m2 reduction in follow-up estimated GFR (using the 4-variable MDRD equation for ages ≥18 years and modified Schwartz for ages \<18 years) compared to baseline estimated GFR
2. 50% decline in follow-up estimated GFR compared to baseline measurement
3. End stage renal disease defined as estimated GFR ≤10cc/min, initiation of maintenance dialysis or preemptive kidney transplantation.
Outcome Measure
Rate of change in renal function.
Outcome Time Frame
60 months
Secondary Ids
Secondary Id
1U54DK083912
Secondary Outcomes
Outcome Description
Patient-reported outcome will be assessed using Quality of Life questionnaires at regular intervals as stipulated in the visit calendar using the SF-36, PedsQL and the Patient Reported Outcome Measurement Information System (PROMIS) (in the age-appropriate groups).
Outcome Time Frame
60 months
Outcome Measure
Quality of Life:
Outcome Description
Any cancer diagnosis of the skin, hematopoietic system, or solid organ after enrollment in NEPTUNE
Outcome Time Frame
60 months
Outcome Measure
Malignancies
Outcome Description
Infections including one of the following:
1. Documented diagnosis of infection of the skin or subcutaneous tissue (e.g. cellulitis), vascular system, peritoneum, or any vital organ requiring the use of parenteral antibiotics and/or oral antibiotics alone or in combination for a treatment interval of ≥72 hours.
2. Hospitalization for treatment of infection
1. Documented diagnosis of infection of the skin or subcutaneous tissue (e.g. cellulitis), vascular system, peritoneum, or any vital organ requiring the use of parenteral antibiotics and/or oral antibiotics alone or in combination for a treatment interval of ≥72 hours.
2. Hospitalization for treatment of infection
Outcome Time Frame
60 months
Outcome Measure
Infections, Serious and Systemic
Outcome Description
Documented diagnosis of one of the following:
1. Embolic cerebrovascular accident
2. Deep venous thrombosis
3. Renal vein thrombosis or
4. Pulmonary embolus
1. Embolic cerebrovascular accident
2. Deep venous thrombosis
3. Renal vein thrombosis or
4. Pulmonary embolus
Outcome Time Frame
60 months
Outcome Measure
Thromboembolic Events
Outcome Description
Documented hospital admission, including observation for ≥24 hours.
Outcome Time Frame
60 months
Outcome Measure
Hospitalization
Outcome Description
Documented visit to an emergency department or observation unit that does not lead to hospitalization and is less than 24 hours.
Outcome Time Frame
60 months
Outcome Measure
Emergency Department/ Observation Unit Visit
Outcome Description
Documented diagnosis of acute kidney injury as defined by the AKIN (Mehta et al., Critical Care 2007, 11:R31) and/or renal failure requiring renal replacement therapy \<3 months.
Outcome Time Frame
60 months
Outcome Measure
Acute Kidney Injury
Outcome Description
1. Documentation of death that is secondary to infection or sepsis.
2. Cardiovascular/Cerebrovascular-related Death: Sudden death; Myocardial infarction; Congestive heart failure; Primary intractable serious arrhythmia; Peripheral vascular disease; Ischemic cerebrovascular accident; Hemorrhagic cerebrovascular accident; Thromboembolic event
3. Documentation of death secondary to cancer
4. Other Death: Documentation of death that does not fall into the above categories.
2. Cardiovascular/Cerebrovascular-related Death: Sudden death; Myocardial infarction; Congestive heart failure; Primary intractable serious arrhythmia; Peripheral vascular disease; Ischemic cerebrovascular accident; Hemorrhagic cerebrovascular accident; Thromboembolic event
3. Documentation of death secondary to cancer
4. Other Death: Documentation of death that does not fall into the above categories.
Outcome Time Frame
60 months
Outcome Measure
Death
Outcome Description
Diagnosis of diabetes as indicated by 1 or more of the following not present at NEPTUNE Enrollment:
1. Documented diagnosis of diabetes in medical record
2. Casual (non-fasting) blood glucose \> 200 mg/dL c) Fasting blood glucose \> 126 mg/dL d) 2 hour glucose \> 200 after oral glucose tolerance test e) chronic use (\>6 mos) hypoglycemic therapy outside of pregnancy f) Hemogloblin A1C \>= 6.5%
1. Documented diagnosis of diabetes in medical record
2. Casual (non-fasting) blood glucose \> 200 mg/dL c) Fasting blood glucose \> 126 mg/dL d) 2 hour glucose \> 200 after oral glucose tolerance test e) chronic use (\>6 mos) hypoglycemic therapy outside of pregnancy f) Hemogloblin A1C \>= 6.5%
Outcome Time Frame
60 months
Outcome Measure
New Onset Diabetes
See Also Links
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Study Population
Patients with signs and symptoms of kidney disease consistent with FSGS, MCD, MN or proteinuric renal disease or pediatric participants not previously biopsied, who present for patient care at participating clinical centers will be eligible for Cohort A (biopsy cohort) study population targeted for enrollment into the NEPTUNE study.
To establish a cohort of pediatric participants with incident nephrotic syndrome, Cohort B, a non-biopsy cohort has been initiated for Protocol V4.0. This population, \<19 years of age, presenting for nephrotic syndrome and less than 30 days of immunosuppression therapy exposure, will also be targeted for enrollment into the cNEPTUNE study.
Potential participants willing to receive their initial care and subsequent follow-up study visits at one of these sites are welcome to participate.
To establish a cohort of pediatric participants with incident nephrotic syndrome, Cohort B, a non-biopsy cohort has been initiated for Protocol V4.0. This population, \<19 years of age, presenting for nephrotic syndrome and less than 30 days of immunosuppression therapy exposure, will also be targeted for enrollment into the cNEPTUNE study.
Potential participants willing to receive their initial care and subsequent follow-up study visits at one of these sites are welcome to participate.
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kimberly Reidy
Investigator Email
kreidy@montefiore.org
Investigator Phone
718-655-1120