6409: Proteomics of Primary HyperoxaluriaType 1 (PHI): A Rare Calcium Oxalate Stone Disease

Status: Active, Not Accruing


Study Summary

The purpose of this study is to identify unique urine protein markers of Primary Hyperoxaluria type I (PHI) compared to healthy controls. Urine protein markers can be identified by “proteomic” analyses in which proteins are processed in a lab to break them down into smaller building blocks. Using analytical chemistry techniques and specialized equipment many proteins can be identified and measured. Most proteins are found in healthy living cells while subtle changes in these proteins or the presence of different markers reflect abnormal processes and patterns of disease. When identified in disease, protein biomarkers can help to determine if a disease responds to new types of therapies. In this study, changes in urine proteomic patterns over time, their association with change in estimated (calculated) kidney filtering function, and the relative risk for progression of PHI will be determined. Additionally, as part of the study, the investigators will measure urinary proteins and peptides that are markers of kidney tissue protection (for healthy healing of the kidneys from ongoing damage from high urine oxalate levels, oxalate crystals and stones) to establish if and when these markers are prospectively decreased in PHI urine. Longitudinal studies of urine “proteomics” may assist in identifying the mechanisms behind PHI-related progression of kidney failure and might contribute important information towards future identification and development of effective therapies to slow or prevent kidney failure in PHI.

For Diseases:

Primary Hyperoxaluria Type I


Primary hyperoxaluria type I (PHI) is a rare genetically inherited disorder seen in 1:100,000-150,000 people and is often underdiagnosed in children. PHI is characterized by abnormally high levels of oxalate in the blood and urine, crystals in the urine, frequent formation of kidney stones, and hardening (calcification) of the kidneys called “nephrocalcinosis.” Identification and evaluation of proteins and peptides (biomarkers) in the urine of PHI patients may provide insight into the process of kidney damage that occurs over time in PHI by evaluating these markers at some point after diagnosis and over long-term. By studying biomarker patterns in the urine of PHI patients that are collected over the course of their disease, information about changes in biomarker patterns over time may provide important clues about those patients at a higher risk for faster progression to end stage kidney failure and may serve as important outcomes for new therapies in the future, too.

Primary study objective: Identify the unique urine proteomic markers of PHI versus healthy intra-familial sibling controls of PHI patient specimens at one point in time (cross-sectionally).

Secondary study objective: Determine change over time in urine proteomic patterns, their association with change in estimated (calculated) kidney filtering function, and the relative risk for progression of PHI and kidney disease progression.

Tertiary study objective: Establish if and when, in the course of PHI, the protective effects of the body (and kidneys) for normal kidney tissue healing are decreased/lost as evidenced by the long-term change in biomarker patterns.   

The goal of the Rare Kidney Stone Consortium (RKSC) is to advance understanding and treatment of severe, rare forms of nephrolithiasis that cause marked excretion of insoluble minerals important in stone formation, including PH, EH, Cystinuria, Dent disease and APRTd. Patients with these disorders experience recurring stones from childhood onward and are at risk for chronic kidney disease. End state renal disease is common in PH, Dent disease and APRTd, with lesser degrees of renal insufficiency observed in Cystinuria. Importantly, these conditions are rare enough that there has been minimal sharing of information and expertise among clinicians and scientists, a situation that has slowed progress toward effective treatments. Over the last 6 years, RKSC has formed secure, web-based registries and tissue banks open for collaborative projects.

About this Study

This is a pilot investigation using previously collected and archived (1) cross-sectional 24 hr. urine samples from PHI patients (n=20) and healthy sibling controls (n=18) and (2) longitudinally collected 24 hr. urine samples from patients with PHI enrolled in the RKSC registry bank (n=55). No new samples will be collected.

Approximately 6 months are required to analyze each set of the biological samples (cross-sectional and longitudinal).

Additional information that will be collected as part of this study: De-identified data from each patient’s medical record including a general health history, medications and supplements taken; history of kidney stones (and their chemical make-up); gender, current age, height, weight; old measurements of urine acidity (pH) and blood oxalate, urine oxalate, calcium, citrate, and creatinine (from muscle breakdown) concentrations, and urine super saturation.

Targeted Enrollment

Please note that this study will use previously collected and archived samples. No new samples will be collected for this study.

To be eligible to participate, you must be an individual who is:

  • Have a previously collected 24 hour urine sample from the Mayo Clinic’s RKSC biobank or already archived at Lurie Children’s Hospital (Chicago, IL), a portion of which has been archived (frozen) for future research because you are a patient who has been diagnosed with primary hyperoxaluria type I that is documented by one of the following: (1) PHI-AGXT mutation confirmed and/or (2) liver biopsy confirmed;
  • Have a previously collected 24 hour urine sample, a portion of which has been archived (frozen) for future research, because you are a sibling of the patient described above.

You are not eligible to participate if you:

  • Have a previously collected 24 hour urine sample because you are a hyperoxaluric patient due to other causes (including secondary hyperoxaluria)
  • Have PHI and have had a 24 hour sample collected but a portion of that specimen has not been archived (frozen) for future research
  • Do not have PHI.

How to participate

In order to participate in a study, you must personally contact the individual at one of the participating institutions noted below by phone or by e-mail. Please use the information below to inquire about participation.


Ann & Robert H. Lurie Children’s Hospital of Chicago, Division of Kidney Diseases, Chicago, IL 60611
Study Co-Investigator: Ellen R. Brooks, Ph.D.
Phone: 312-227-6167
E-mail: e-brooks3@northwestern.edu
Principal Investigator: Craig B. Langman, MD
Co-Investigator: Ellen R. Brooks, Ph.D.


Mayo Clinic Rare Kidney Stone Consortium, Rochester, MN 55905
Study Coordinators: Barb Seide & Julie Olson, RN
Phone: 800-270-4637
E-mail: hyperoxaluriacenter@mayo.edu
Principal Investigator: Dawn S. Milliner, MD