Genetic Markers for Focal Segmental Glomerulosclerosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001393
First received: November 3, 1999
Last updated: March 14, 2014
Last verified: February 2014
  Purpose

Glomerulonephritis is a disease which affect the kidneys. Occasionally these diseases can progress to a loss of kidney function in some patients. Glomerulosclerosis or focal segmental glomerulosclerosis (FSGS) is one form of glomerulonephritis.

The cause of FSGS is unknown and often occurs on its own (idiopathic), or it can be associated with HIV (Human Immunodeficiency Virus). FSGS occurs more commonly among black patients than Caucasian or Hispanic patients. Researchers believe that environmental factors may interact with genetic mutations to cause FSGS, at least in some patients.

This study will attempt to identify genetic factors associated with the development of FSGS. The study population will be made up of 600 total subjects divided into 3 groups. Group one will be 200 African-Americans with FSGS. Group two will be 200 African-Americans with HIV but without FSGS. Group three will be 200 non-African-Americans with FSGS.

Study participation requires that researchers obtain 20 ml (2 tubes of blood). The genetic material (DNA) will be prepared from the white blood cells and analyzed. The results of each group will be compared with the results from the other groups to determine if one or more genes predisposes to FSGS. In the long run, studies that demonstrate a genetic basis for FSGS may help us identify patients earlier and may lead to improved therapies....


Condition
AIDS Associated Nephropathy
Focal Glomerulosclerosis
HIV Infections

Study Type: Observational
Official Title: Genetic Markers for Focal Segmental Glomerulosclerosis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Study Start Date: April 1994
Detailed Description:

Focal segmental glomerulosclerosis (FSGS) and a related condition, collapsing glomerulopathy, are chronic renal diseases affecting the glomerular podocytes. Currently, over thirteen genetic mutations are associated with FSGS. We are interested in expanding our understanding of these and other genes that may cause FSGS and collapsing glomerulopathy. We will study individuals with affected family members. We will also study sporadic cases; the rationale for studying this population is that FSGS and collapsing glomerulopathy are significantly more common among individuals of African descent. The latter observation suggests that particular FSGS-susceptibility alleles may be more common among African Americans. In the present study, we are addressing the hypothesis that genetic variation contributes to the pathogenesis of idiopathic FSGS and collapsing glomerulopathy, both idiopathic and HIV-associated variants.

We are studying the following groups:

  1. African-Americans with idiopathic or HIV-associated collapsing glomerulopathy. We will exclude post-adaptive FSGS, associated with glomerular hyperfiltration, and medication associated FSGS.
  2. Other patients with idiopathic FSGS< TAB>
  3. African Americans with HIV and without kidney disease (hypernormal controls)
  4. African American blood donors (normal controls)< TAB>
  5. Healthy Caucasian controls (controls)< TAB>
  6. Relatives of patients with familial FSGS< TAB>
  7. Kidney donors

We are taking three methodologic approaches. First, we are examining known FSGS risk genes or candidate genes, looking for disease-causing mutations and for disease-susceptibility haplotypes. Second, we have undertaken a genome scan, in the African American population. We may also undertake a whole genome scan in European Americans. Evidence of linkage disequilibrium among these markers will be sought between patients with and without FSGS. Third, when we identify families with multiple affected individuals and which lack known genetic mutations affecting FSGS genes, we will pursue positional cloning.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

All patients with idiopathic FSGS and idiopathic and HIV-associated collapsing glomerulopathy, and kidney donors are eligible.

AFRICAN-AMERICANS WITH FSGS:

Renal biopsy showing FSGS or collapsing glomerulopathy, including HIV-associated collapsing glomerulopathy (HIV-associated nephropathy).

We will include adult and pediatric patients.

OTHER PATIENTS WITH FSGS:

Renal biopsy showing FSGSor collapsing glomerulopathy, including HIV-associated collapsing glomerulopathy (HIV-associated nephropathy).

We will include adult and pediatric patients.

AFRICAN AMERICANS WITH HIV AND WITHOUT KIDNEY DISEASE (CONTROLS):

We will include adult patients who have had serologically confirmed HIV-1 infection for at least 8 years and lack clinical renal disease, as evidenced by normal creatinine and urine protein/creatinine ratio less than 0.5 or 24 hour urine protein excretion less than 500 mg/d.

AFRICAN AMERICAN BLOOD DONORS (CONTROLS):

We will include adults only.

HEALTHY CAUCASIAN CONTROLS (CONTROLS):

These samples represent DNA already obtained.

RELATIVES OF PATIENTS WITH FSGS:

In selected families (in which a patient has been found to have a mutation in a FSGS risk gene whose pathologic role has not been established), we will obtain individual histories of renal disease (hematuria, proteinuria, hypertension,nehrolithiasis) and will measure serum creatinine and urine protein excretion. We will include adults with and without renal disease and children with renal disease. We will evaluate children less than 18 years by obtaining a urine sample; if urinalysis and urine protein excretion are normal, we will not a request a blood sample.

KIDNEY DONORS:

We will include NIH kidney donors only. We will obtain individual histories that provide information as to age, sex, race, surgical and medical histories, and family history. Dr. Cho, as part of another protocol, will measure urinary albumin and kidney size (which by comparison with radiologic studies done at the time of kidney donation will allow determination of kidney hypertrophy following donation). Our purpose is to examine whether particular genetic variants, including those in MYH9, influence the ability of the kidney to undergo hypertrophy following renal donation or the propensity to manifest albuminuria as a sign of glomerular stress. These findings have the potential to extend our understanding of the biology of MYH9 and might have clinical relevance for selecting kidney donors.

EXCLUSION CRITERIA:

AFRICAN-AMERICANS WITH FSGS:

We will exclude patients with hyperfiltration FSGS (reduced renal mass, chronic interstitial nephritis, sickle cell anemia, obesity with BMI greater than 40 kg/m(2)).

OTHER PATIENTS WITH FSGS:

No patients with hyperfiltration FSGS (reduced renal mass, chronic interstitial nephritis, sickle cell anemia, obesity with BMI greater than 40 kg/m(2)).

AFRICAN AMERICAN BLOOD DONORS (CONTROLS):

HIV-1 infection.

Renal disease.

HEALTHY CAUCASIAN CONTROLS (CONTROLS):

Patients will not be recruited as part of the present study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001393

Contacts
Contact: Anaida Widell (301) 451-9946 awidell@cc.nih.gov
Contact: Jeffrey B Kopp, M.D. (301) 594-3403 jeffreyk@mail.nih.gov

Locations
United States, Maryland
University of Maryland, Baltimore Recruiting
Baltimore, Maryland, United States, 21201-1595
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15261
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Israel
Tel Aviv University Recruiting
Tel Aviv, Israel
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey B Kopp, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001393     History of Changes
Other Study ID Numbers: 940133, 94-DK-0133
Study First Received: November 3, 1999
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
HIV
Renal Disease
African-Americans
HIV Associated Nephropathy

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Glomerulosclerosis, Focal Segmental
Kidney Diseases
AIDS-Associated Nephropathy
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Glomerulonephritis
Nephritis
Urologic Diseases

ClinicalTrials.gov processed this record on August 21, 2014