Investigation of genetic factors in diabetic kidney disease

Family Investigation of Nephropathy and Diabetes (F.I.N.D.)

This study is trying to find out if certain genes make people with diabetes more likely to develop kidney disease, especially in American Indian and indigenous Micronesian communities.

Quick facts

• Study type: Observational
• Enrollment: 100000 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Locations: 1 site (Phoenix, Arizona)
• Trial ID: NCT00342927 on ClinicalTrials.gov

What this trial studies

The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter observational study aimed at identifying genetic determinants of diabetic kidney disease across various ethnic groups in the United States. It employs two strategies: a family-based genetic linkage study and a case-control study utilizing admixture linkage disequilibrium. Participants with diabetes and kidney disease, along with their family members, are recruited to provide genetic material for analysis. The study focuses particularly on American Indian populations and indigenous Micronesian populations, aiming to uncover chromosomal regions linked to susceptibility to diabetic nephropathy.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 18 and older with diabetes and severe diabetic nephropathy, along with their family members.

Not a fit: Patients without diabetes or those with mild forms of kidney disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and potential prevention strategies for diabetic kidney disease.

How similar studies have performed: Other studies have shown success in identifying genetic factors related to diabetic kidney disease, making this approach promising.

Eligibility criteria

* INCLUSION CRITERIA:

Index Cases:

Individuals with diabetes and diabetic nephropathy who are at least 18 years of age.

Potential index cases must have at least one sibling, or both parents available as potential study participants.

Potential index cases must also have diabetic nephropathy. An index case must have nephropathy that is more severe than microalbuminuria. An index case must meet one of the following criteria:

1. Biopsy proven diabetic nephropathy (by medical record review):

   1. Nodular and/or diffuse increases in the mesangial matrix accumulation; and
   2. Thickened glomerular basement membranes and/or arteriolar hyalinization; and
   3. Absence of mesangial immunoglobulin or paraprotein deposits by immunoflorecscence microscopy, absence of amyloid deposits by Congo Red staining or electron microscopy, absence of electron dense deposits within the glomerular basement membrane or glomerular capillary subendothelial space; and
   4. Overt proteinuria, defined as ACR greater than or equal to 300 mg/g, urinary protein creatinine ratio greater than or equal to 0.5 g/g, urinary albumin excretion greater than or equal to 300 mg/24 hr, or urinary protein excretion greater than or equal to 0.5 g/24 hr.
2. ESRD (including transplant) from presumed diabetic nephropathy:

   Diabetes present for at least 5 years prior to the initiation of replacement therapy and retinopathy at any time;

   or Diabetes present for at least 5 years prior to the initiation of replacement therapy and either greater than or equal to 3 gm protein/24 hours, or a urine protein (mg)/creatinine (mg) greater than or equal to 3.0 or urinary ACR greater than or equal to 3000 mg/g or urinary albumin excretion greater than or equal to 3000 mg/24 hours (historical data acceptable);

   or retinopathy and either greater than or equal to 3 gm protein/24 hours, or a urine protein (mg)/creatinine (mg) greater than 3.0 or urinary ACR greater than or equal to 3000 mg/g or urinary albumin excretion greater than 3000 mg/24 hours (historical data acceptable).
3. Patient with presumed diabetic nephropathy but not ESRD:

Patient has diabetic retinopathy and either greater than or equal to 1 gram proteinuria/24 hours or a urine protein (mg)/creatinine (mg) greater than or equal to 1.0 or urinary ACR greater than or equal to 1000 mg/g or urinary albumin excretion greater than or equal to 1000 mg/24 hours (historical data acceptable);

or first detection of either greater than or equal to 3 gram protein/24 hours or a urine protein (mg)/creatinine (mg) greater than or equal to 3.0 gram or urinary ACR greater than or equal to 3000 mg/g or urinary albumin excretion greater than or equal to 3000 mg/24 hours at DM duration greater than or equal to 10 years (historical data acceptable).

Recruitment of Family Members:

Any available parent or sibling who is at least 18 years of age will be recruited as a potential participant and will use the same criteria as above.

DNA for individuals in informative families will be submitted to the genotyping laboratory. An informative family is defined as one for which DNA specimens are available for the following individuals:

1. The index case and both parents, or
2. The index case and at least one other affected sibling who has diabetes and renal disease, or
3. The index case and at least one unaffected sibling, defined as an individual who has had diabetes for at least 10 years and who has no renal disease (based on evidence obtained from the medical record and from the FIND examination.

Where this trial is running

Phoenix, Arizona

• NIDDK, Phoenix — Phoenix, Arizona, United States (RECRUITING)

Study contacts

• Principal investigator: Robert L Hanson, M.D. — National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Study coordinator: Robert L Hanson, M.D.

Conditions: Diabetic Nephropathy, Diabetes Mellitus, Diabetic Kidney Disease, Albuminuria, American Indians, Complications, Genetics, Linkage