proteomics of primary hyperoxaluria type 1

Conditions: Primary Hyperoxaluria Type 1

Summary: the purpose of this study is to identify unique urine protein markers of primary hyperoxaluria type 1 (ph1) 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 ph1 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 ph1 urine. longitudinal studies of urine "proteomics" may assist in identifying the mechanisms behind ph1-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 ph1.

primary hyperoxaluria type 1 (ph1) is a rare genetically inherited disorder seen in 1:100,000-150,000 people and is often underdiagnosed in children. ph1 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 ph1 patients may provide insight into the process of kidney damage that occurs over time in ph1 by evaluating these markers at some point after diagnosis and over long-term. by studying biomarker patterns in the urine of ph1 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 ph1 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 ph1 and kidney disease progression. tertiary study objective: establish if and when, in the course of ph1, 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 primary endpoints of this study include standard clinical endpoints (data that a kidney doctor would look at as a ph1 patient would be followed over time in the clinic), as they best reflect ph1 disease progression: (a) estimated glomerular filtration rate (egfr), known as kidney filtering function; (b) urine oxalate; and (c) plasma oxalate (when egfr \< 40 ml/min/1.73 m2, which is when kidney function is significantly decreased). 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 in which patients experience recurring stones from childhood onward and are at risk for chronic kidney disease. end state renal disease is common in ph1. 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 ph1 patients (n=20) and healthy sibling controls (n=18) and (2) longitudinally collected 24 hr. urine samples from patients with ph1 enrolled in the rksc registry bank (n=55). no new samples will be collected. additional information that will be collected (or provided with the urine specimens) as part of this study: de-identified data from each patient's 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, and blood oxalate, urine oxalate, calcium, citrate, and creatinine (from muscle breakdown) concentrations, and urine super saturation.

Eligibility criteria:
inclusion criteria: * have a previously collected 24 hour urine sample from the mayo clinic's rare kidney stone consortium (rksc) biobank or previously stored 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 1 (ph1) that is documented by one of the following: (1) ph1 mutation confirmed and/or (2) liver biopsy confirmed; or * have a previously collected 24 hour urine sample, a portion of which has been archived (frozen) for future research, because you are a healthy sibling of a ph1 patient, as described above. exclusion criteria: * have a previously collected 24 hour urine sample because you are a hyperoxaluric patient due to other causes (including secondary hyperoxaluria); * have ph1 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 ph1.