Over the past 30 years much has been learned about the molecular genetics and natural history of familial forms of hematuria. However, the enhanced understanding of these conditions has yet to generate effective therapies for Alport syndrome, the form of familial hematuria associated with end-stage renal disease. Males with Alport syndrome inevitably develop end-stage kidney failure, with a 50% likelihood of dialysis or kidney transplantation by age 25 years. There is no proven treatment for Alport syndrome, although studies in animals have suggested several promising potential therapies. Potential drug treatments that might delay or prevent the development of kidney failure exist, but need to be evaluated through clinical trails. Conducting clinical trails for proposed treatments for Alport syndrome present many challenges. Because Alport syndrome is not a common disease, informative clinical trials will require the collaboration of investigators at multiple centers.

The University of Minnesota, Department of Pediatrics, proposes to create the Alport Syndrome Treatments and Outcomes Registry (ASTOR) in order to facilitate clinical trials for the treatment of Alport Syndrome. This registry will be the first of its kind in North America. Because Alport syndrome is a rare disorder, recruitment of sufficient participants for meaningful therapeutic trials will require a multicenter effort. The primary objective of establishing and sustaining this registry is to enable clinical natural history studies and therapeutic trials to be conducted in children and adolescents with Alport syndrome.

Detailed Description:

ASTOR is envisioned as a permanent organization sustained by private philanthropic and public funding sources. Recruitment of participants for the registry will consist of three approaches. First, pediatric nephrologists in the United States and Canada will be invited to participate in ASTOR. Activities of participating investigators will include identification and recruitment of potential study participants, collection and transmission of participant data to the ASTOR central office at the University of Minnesota, and implementation of study protocols.

Participating physicians will inform their participants and parents about ASTOR and invite them to participate in writing. The correspondence will include instructions on how to contact ASTOR personal about formal participation. Participants and their parents will be asked to permit sharing of their personal health information with the ASTOR central office.

Second, the ASTOR central office will develop a website for participants and families. The website will provide participants and families with medical and new research information and instructions on how to contact registry staff about registry participation. Potential participants who contact the central office will be asked to give consent for ASTOR staff to contact their health care providers.

Third, the University of Utah School of Medicine's Department of Nephrology, currently holds data pertaining to approximately 350 families with a reported history of Alport syndrome. Department investigators have agreed to provide information that will ultimately assist ASTOR staff in executing recruitment activities by providing historical medical health information pertaining the natural progression of the disease and current treatment practices and by contacting patients in the existing database to determine if any individuals or families are interested in participating in the registry. This information will be used to support analysis efforts that may come about as a result of new studies that are developed or implemented under the aegis of the registry. 

Selection and Enrollment of Participants

Each consented participant will be assigned a unique identifier and entered into the ASTOR database, along with demographic data, health information and urine analysis results. Referring physicians and their home institutions will also be assigned unique identifiers.

ASTOR coordinator will contact each participant's physician and provide instructions on how to complete a detailed baseline questionnaire designed to capture the following information:

Family history

• X-chromosomal inheritance
• Autosomal inheritance
• Mode of inheritance unknown
• Mode of inheritance known: Which person of your family is/was effected (or indicate in family tree), which symptoms (hearing defect, ocular abnormalities, renal disease, leiomyomatosis)?
• At what age was the diagnosis Alport syndrome was made in effected family members?
• If a family member had end stage renal failure, at what age?

Individual data of treated participant

• At what age the diagnosis of Alport syndrome was made?
• Has a skin biopsy been performed? If yes, list results.
• Has a kidney biopsy been performed? If yes, list results.
• Has a molecular-genetic diagnosis/ mutation analysis been performed?

Clinical data and progress of disease

• Medications and the age these meds were started

Recruitment of participants for the registry will consist of three approaches. First, pediatric nephrologists in the United States and Canada will be invited to participate in the Alport Syndrome Treatments and Outcomes Registry (ASTOR). Activities of participating investigators will include identification and recruitment of potential study participants, collection and transmission of participant data to the ASTOR registry's central office at the University of Minnesota. Second, the ASTOR central office will develop a website for participants and families. The website will provide participants and families with medical and new research information and instructions on how to contact registry staff about registry participation. All policies and procedures for the information or samples that are shared, stored or banked by the ASTOR central office will be prepared in accordance with the University of Minnesota Office of Information Technology standard for securing private data (see data safety monitoring plan). Urine samples will be collected by the ASTOR central office. Instructions and materials for collecting and mailing the specimens will be provided to each participant.  Third, the University of Utah will contact their existing patient base to determine if any individuals or families are interested in participating in the registry (IRB approval will be sought to contact potential participants). Interested participants will be referred to the ASTOR central office. Interested individuals and families will be contacted in writing about formal participation.     

ASTOR central office staff will obtain informed consent form all participants (telephone consent IRB approval pending). Participants will be seen every six months for assessments. Clinical assessments will include an initial baseline questionnaire and urine sample followed with bi-annual updates on medical and medication histories and urine analysis.

Medical and medication histories will be completed by the participant's provider and urine samples will be forwarded by the participant to the University of Minnesota's central office for testing. Contractual agreements for the processing of all urine samples will be will be established with an in-state laboratory .

Data Collection and Site Monitoring

Data to be Collected by Study Personnel:

1. Participant consent for the study (includes participant and parental consent, participant assent when appropriate)

2. Baseline Questionnaire with bi annual medication and medical updates c. Baseline urine sample repeated bi annually

   Participant's medical and clinical data and urine analysis results will be submitted to the ASTOR central office from multiple sources. Our goal is that all participants by 4 months would have complete study data (acknowledgement of consent, completed baseline questionnaire and urine sample results) and data entry into an ASTOR central office data base. Performance and completion of these components do not have participant or participant safety implications.

   • Data accuracy: For each participant, the data entered will match with the hard copy of the questionnaire and lab and results. Opportunities for error will be minimized by the elimination of the need to re-copy data to multiple locations. Copies of all source documents will be filed in double locked environments.

   • Data Confidentiality: Every participant will be assigned a unique identifying registry number. These unique participant identifiers will be kept within individual participant folders. These participant folders are kept in files that are locked, with only study specific personnel having access to them.

   Participant data in computer databases are accessible only by study personnel require and require a password. Participant specific information will not be included in publications or in presentations at local or national meetings or conferences.

   • Data Use: Registry participant data regarding medical history, urine analysis, and demographic data will be used to define and categorize participants for future research studies. Participant will be informed of the intended use and sign a formal consent to participate in any future research endeavors that may be developed and implemented.

   The database will also be useful in providing study personnel with the specific dates for ensuing visits beginning with baseline and all subsequent bi-annual evaluations. No one outside of immediate study staff will have access to the participant data, and password protection is in place on each of the study computers to reduce the chance of any breach in confidentiality.

   There may be occasional requests from investigators outside the immediate study personnel to share information. Information will be provided to investigators in accordance with University of Minnesota Data Monitoring and Safety policies.

Inclusion criteria:

• Age < 30
• Diagnosis of Alport syndrome, confirmed by skin biopsy, kidney biopsy, or molecular genetic analysis or diagnosis of Alport syndrome, based on presence of hematuria and confirmed diagnosis of Alport syndrome in a first-degree relative
• Normal renal function, as measured by serum creatinine or estimated or measured creatinine clearance

Exclusion Criteria:

• Uncertain diagnosis of Alport syndrome