Urinary Biomarkers of the Progression of Alport Kidney Disease

This is a prospective cross-sectional, observational, single-center study of affected Alport
patients who have not progressed to advanced chronic renal insufficiency (CKD Stages 4 or
5), and who do not have nephrotic range proteinuria (urine protein-to-creatinine ratio > 3).
There will be no required study site visits. Instead, encounters will occur via telephone
with subjects when they are at home. This study consists of a single, first morning voided
urine collection for subjects who meet eligibility criteria. Eligibility criteria and
informed consent can be obtained via telephone in order to be as non-intrusive to the
subject as possible.

Alport subjects will be recruited via the Alport Syndrome Treatments and Outcome Registry
(ASTOR, University of Minnesota). ASTOR is the largest Alport Syndrome registry in the USA,
comprised of approximately 500 people affected by Alport Syndrome. Subjects who meet
eligibility criteria will be asked to provide clinical and demographic information and a
single urine sample. A portion of the de-identified sample will be sent to Covance
Laboratories for processing for Novartis and the remainder will be processed, stored and
analyzed at the University of Minnesota. Subjects who provide consent will be given a kit
and instructions for collecting the urine sample. Kits will then be returned via overnight
courier to the study site. ASTOR study personnel will then communicate with subjects via the
telephone to confirm proper first-morning void collection technique, and to obtain clinical
historical information.

Approximately 80 Alport subjects will be enrolled in this study via ASTOR. Of the 80 Alport
subjects, approximately 25% (N = 20) should have no significant proteinuria (spot urine
protein-to-creatinine ratio ≤ 0.2), and approximately 75% (N = 60) should have non-postural,
non-nephrotic proteinuria (defined as spot urine protein-to-creatinine ratio > 0.2 and < 3
on at least 2 of the last 3 clinical assessments). Approximately 40 healthy volunteers will
provide urine samples elsewhere, outside the scope of this protocol. Healthy volunteer urine
samples need not be first-morning voided specimens, however each specimen will be screened
via dipstick for semi-quantitative protein analysis. Only samples with negative or trace
protein on dipstick will be included in the study.

Informed consent forms will be included in the kit sent to each eligible Alport subject.
Informed consent will take place via telephone, and preferably via video chat/Skype whenever
possible.

Inclusion Criteria:

Subjects eligible for inclusion in this study have to fulfill all of the following
criteria:

1. Able to understand and comply with the requirements of the study and able to provide
written informed consent.

2. Male and female subjects ≥ 5 years of age.

3. Physically able to provide a single first-morning urine sample of at least 30 mL (one
ounce).

4. Alport syndrome diagnosis: Clinical and/or histopathologic and/or genetic diagnosis
of Alport Syndrome, as per the subject's physician and/or genotyping.

Exclusion Criteria:

Subjects fulfilling any of the following criteria are not eligible for inclusion in this
study:

1. Use of investigational drugs at the time of enrollment, or within 30 days or 5
half-lives of enrollment, whichever is longer; or longer if required by local
regulations, and for any other limitation of participation in an investigational
trial based on local regulations.

2. Chronic kidney disease, defined as a known diagnosis of CKD, and/or receiving chronic
phosphate-lowering therapy or erythropoietin therapy.

3. Ongoing chronic hemodialysis therapy and/or renal transplant recipient.

4. Nephrotic-range proteinuria: spot urine protein-to-creatinine ratio ≥ 3 on at least 2
of the last 3 clinical assessments.