Primary hyperoxaluria (PH) is the most severe of the stone diseases, causing recurring stones from childhood on and end stage renal failure. Progress toward effective treatments has been slow. Our experience with the International Primary Hyperoxaluria Registry (IPHR) has resulted in better understanding of disease expression, early recognition of factors associated with loss of renal function, has suggested treatment strategies likely to be successful, and has facilitated sufficient numbers of patients to test new treatments in clinical trials of betaine and Oxalobacter, to date. The goals of the current project are to: (1) Expand our current PH registry to determine the factors associated with nephrocalcinosis, stone formation, and renal injury (2) Generate testable hypotheses regarding mechanisms of renal injury in these diseases through registry findings, tissue resources, and pilot projects. (3) Explore new avenues of treatment. (4) Develop cohorts of well-characterized patients for future clinical studies, (5) Explore new areas of partnership with the Oxalosis and Hyperoxaluria Foundation (OHF) (6) Provide ready access to high quality resources and information for physicians and scientists and (7) Attract and train investigators to rare diseases research. We will accomplish these goals through a consortium of clinician and basic scientists expert in PH, a network of study sites, and close collaboration with the OHF to more effectively reach and educate health care providers and patients. The 4 Specific Aims are to: S.A. 1a. Expand the PH registry containing clinical data for longitudinal follow-up of patients, identifying wellcharacterized cohorts of patients available for future treatment studies. 1 b. Expand the PH tissue bank S.A. 2a. Identify genetic modifiers of disease expression, specifically early onset of ESRD 2b. Perform molecular screening of TGF p as a candidate modifier gene. S.A. 3. Evaluate hydroxyproline as a potential metabolic precursor of oxalate in PH types 1 and 2. S.A. 4a. Create web-based educational materials at the highest scientific and medical level, to allow creation of patient material by the Oxalosis and Hyperoxaluria Foundation for international dissemination. 4b. Provide high quality information and resources regarding PH for physicians, clinical and basic scientists. We will also apply our experience with the IPHR to create a similar structure and activities for other hereditary causes of nephrolithiasis and renal failure: cystinuria, APRT deficiency, and Dent disease. Synergies will allow rapid transfer of experience and advancement of patient care.

Public Health Relevance

Progress toward more effective treatment for patients with primary hyperoxaluria has been slow due the rarity of this condition. To address this problem we will further develop the International Primary Hyperoxaluria Registry and tissue bank, augment collaborations with key scientists, conduct pilot projects, and explore new areas of partnership with the OHF to engage patients and their physicians in order to better characterize disease expression, generate innovative hypotheses, and test new treatments.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Lieske, John C (2018) Bariatric Surgery and Kidney Health. J Am Soc Nephrol 29:1085-1086
Edvardsson, Vidar O; Runolfsdottir, Hrafnhildur L; Thorsteinsdottir, Unnur A et al. (2018) Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with Adenine phosphoribosyltransferase deficiency (APRTd): A clinical trial. Eur J Intern Med 48:75-79
Goldfarb, David S (2018) Empiric therapy for kidney stones. Urolithiasis :
Thorsteinsdottir, Margret; Thorsteinsdottir, Unnur A; Eiriksson, Finnur F et al. (2018) Corrigendum to ""Quantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency"" [J. Chromatogr. B 1036-1037 (2016) 170-177]. J Chromatogr B Analyt Technol Biomed Life Sci 1092:530
Shah, Ronak Jagdeep; Lieske, John C (2018) Inching toward a Greater Understanding of Genetic Hypercalciuria: The Role of Claudins. Clin J Am Soc Nephrol 13:1460-1462
Tasian, Gregory E; Jemielita, Thomas; Goldfarb, David S et al. (2018) Oral Antibiotic Exposure and Kidney Stone Disease. J Am Soc Nephrol 29:1731-1740
Policastro, Lucas J; Saggi, Subodh J; Goldfarb, David S et al. (2018) Personalized Intervention in Monogenic Stone Formers. J Urol 199:623-632
Nazzal, Lama; Blaser, Martin J (2018) Does the Receipt of Antibiotics for Common Infectious Diseases Predispose to Kidney Stones? A Cautionary Note for All Health Care Practitioners. J Am Soc Nephrol 29:1590-1592
Runolfsdottir, Hrafnhildur Linnet; Palsson, Runolfur; Agustsdottir, Inger MSch et al. (2018) Long-term renal outcomes of APRT deficiency presenting in childhood. Pediatr Nephrol :
Dhondup, T; Lorenz, E C; Milliner, D S et al. (2018) Combined Liver-Kidney Transplantation for Primary Hyperoxaluria Type 2: A Case Report. Am J Transplant 18:253-257

Showing the most recent 10 out of 95 publications