Pathogenesis of Glomerulosclerosis
2 other identifiers
observational
537
1 country
1
Brief Summary
The present protocol seeks to advance our understanding of sclerosing glomerular and tubulointerstitial kidney diseases, including but not limited to variants of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease of unknown etiology (CKDu). This protocol will encompass studies of the natural history, pathogenesis and treatment of these chronic kidney disorders. It will also allow us to: (1) provide second opinions to referring physicians about management of subjects with these relatively rare kidney diseases; (2) collect research samples (e.g., blood), urine, and kidney tissue obtained from clinically-indicated or from research renal biopsies); (3) and treat these subjects with standard or other approved therapies; or (4) invite selected subjects patients to participate in limited pilot studies of novel combinations of standard therapeutic agents, such as rituximab and cyclosporine. (5) Agricultural worker chronic kidney disease of undetermined etiology (CKDu) is a growing problem in tropical countries in the Americas and Asia, including Sri Lanka where collaborators are located. We will receive kidney tissue from 25 CKDu cases for pathologic examination and transcriptional profiling and blood, plasma, serum, urine for metabolomic and genetic analysis from 50 cases and controls. Subjects were consented and samples were collected under a protocol approved by the University of Colombo IRB. These studies may provide the opportunity to generate new hypotheses regarding pathogenesis and treatment that would be candidates for testing in other research protocols. Subjects with known or suspected forms of sclerosing glomerular or chronic, fibrosing tubulointerstitial kidney diseases will undergo routine medical evaluation, laboratory testing, imaging procedures and kidney biopsies as medically indicated. Selected subjects will be invited to provide informed consent to undergo a kidney biopsy for research purposes. Blood, urine, and tissue samples will be evaluated both for standard diagnostic purposes and for research purposes using specialized molecular methods that may provide insights into specific disease pathogenesis. Subjects may elect to receive the results of their kidney disease evaluation, NIH treatment recommendations, and return to the care of their referring physicians. Other subjects may be treated with either conventional or approved agents, or (with separate consent) with a novel combination of conventional therapies (rituximab and cyclosporine) as part of pilot studies that would involve long-term follow-up care at the NIH.
Trial Health
Trial Health Score
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participants targeted
Target at P75+ for all trials
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Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 16, 1996
CompletedFirst Submitted
Initial submission to the registry
November 3, 1999
CompletedFirst Posted
Study publicly available on registry
November 4, 1999
CompletedMay 1, 2026
April 20, 2026
November 3, 1999
April 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
new hypotheses
To generate new hypotheses regarding pathogenesis and treatment that would be candidates for testing in other research protocols.
one year
Study Arms (1)
Study Cohort
Subjects with known or suspected forms of sclerosing glomerular or chronic, fibrosing tubulointerstitial kidney diseases
Eligibility Criteria
Subjects with known or suspected glomerular or tubulointerstitial disease will be eligible for study. No sex, race or ethnic selection will be applied. It is anticipated the African-Americans will predominate, given the increased risk of FSGS in this population. For evaluation, treatment, and pathogenetic studies, we will enroll children \>=2 years of age and adults, including pregnant women and impaired subjects, if they have known or suspected forms of the kidney diseases described above. For pathogenetic studies not involving interventional procedures such as renal biopsies, we will also include healthy volunteers, including children \>=12 years of age and adults. We will also recruit subjects including children \>=12 years of age and adults with autoimmune and inflammatory diseases, both with and without kidney disease, to serve as controls for subjects with the sclerosing glomerular kidney diseases that are the primary focus of this protocol.
You may qualify if:
- An unlimited number of subjects with known or suspected glomerular or tubulointerstitial disease will be eligible for study. No sex, race or ethnic selection will be applied. It is anticipated the African-Americans will predominate, given the increased risk of FSGS (focal segmental glomerulosclerosis) in this population.
You may not qualify if:
- None
- WHOLE EXOME/GENOME SEQUENCING
- ELIGIBLITY FOR WHOLE EXOME/GENOME SEQUENCING:
- Subjects with kidney disease
- Unexplained kidney disease, family history of kidney disease, or other kidney disease suggestive of a genetic origin, excluding FSGS
- Age greater than or equal to 2 years
- Subjects without kidney disease
- Family member with unexplained kidney disease, family history of kidney disease, or other kidney disease suggestive of a genetic origin, excluding FSGS
- Age greater than or equal to 18 years
- Able to provide informed consent
- RITUXIMAB AND CYCLOSPORINE. (CLOSED FOR SUBJECT RECRUITMENT.)
- First void urine protein to creatinine ratio \> 2g/g despite optimal use of an ACE inhibitor or ARB (or possibly both), last dose increase at least 4 weeks before qualifying proteinuria determination
- Women must use reliable birth control method to avoid pregnancy while participating in the study.
- Subjects who have failed to respond with a complete remission or partial remission after at least 8 weeks of prednisone at a dose of at least 60 mg or are steroid dependent or relapse off steroids.
- Subjects who have compelling contraindications to the use of glucocorticoids, such as morbid obesity, defined as BMI \>35 or diabetes mellitus
- +47 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anirban Ganguli, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 3, 1999
First Posted
November 4, 1999
Study Start
April 16, 1996
Last Updated
May 1, 2026
Record last verified: 2026-04-20
Data Sharing
- IPD Sharing
- Will not share
Sharing of IPD is not consistent with the consents for this study. Data has been published in three peer-reviewed journal articles, listed here: @@@@@@Orloff MS, Iyengar SK, Winkler CA, Goddard KA, Dart RA, Ahuja TS, et al. Variants in the Wilms' tumor gene are associated with focal segmental glomerulosclerosis in the African American population. Physiol Genomics. 2005;21(2):212-21.@@@@@@Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet. 2008;40(10):1175-84.@@@@@@Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841-5.