6417: Prospective Research Rare Kidney Stones (ProRKS)

Status: Recruiting

The purpose of this study is to determine the natural history of the hereditary forms of nephrolithiasis and chronic kidney disease, primary hyperoxaluria (PH), cystinuria, Dent disease, Lowe Syndrome, adenine phosphoribosyltransferase deficiency (APRTd) as well as enteric hyperoxaluria (EH), which is usually acquired later in life. The investigators will measure blood and urinary markers of inflammation and determine the relationship between these markers and the course of the disease. Cross-comparisons among the disorders will allow us to better evaluate mechanisms of renal dysfunction in these disorders.

For Diseases:

  • Primary Hyperoxaluria
  • Enteric Hyperoxaluria
  • Cystinuria
  • Dent Disease
  • Lowe Syndrome
  • Adenine Phosphoribosyltransferase Deficiency (APRTd)


Severe, hereditary forms of nephrolithiasis, including PH, Cystinuria, Dent disease, and APRTd, can each cause markedly increased elimination of insoluble materials by the kidney such as calcium, oxalate, cystine, and dihydroxyadenine. Patients with these disorders experience recurring stones from childhood and are at high risk for chronic kidney disease caused by crystal nephropathy. EH is an acquired disease characterized by hyperoxaluria and calcium oxalate crystal nephropathy associated with chronic kidney disease, and in that respect similar to the inherited stone diseases. The investigators will collect longitudinal data of individual patients in order to provide clues about factors that may be able to be changed that influence disease severity. The investigators will also try to identify factors leading to kidney injury.

Primary study objective: Establish a prospective longitudinal cohort of patients with PH, EH, Cystinuria, Dent disease, Lowe syndrome and APRTd to identify biomarkers associated with disease progression.

Secondary study objective: Identify pathways of kidney injury associated with PH, EH, Cystinuria, Dent disease, Lowe syndrome and APRTd.

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 on 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 prospective longitudinal cohort study of human subjects. Six groups of patients will be studied: patients with PH, EH, Cystinuria, Dent disease, Lowe syndrome and APRTd.

  • PH patients: 60
  • EH patients: 30
  • Cystinuria patients: 50
  • Dent patients (Dent1 or non 1 or 2 Dent): 30
  • Lowe syndrome or Dent 2 patients: 10
  • APRTd patients: 30
  • Dent 1 carriers: 10

This is a 5 year study. We are asking patients to return once a year for an annual clinical checkup. These annual exams, tests or procedures are part of regular clinical care and may be done even if the patient does not join the study.

Each year at an annual visit, the following will be included as part of routine clinical care (this will be used in the research study):

  • Physical exam by a physician
  • Height, weight and blood pressure measurements
  • Blood sample collection (about 3 tablespoons)
  • 24 hour urine collection or random urine for younger patients who are unable to complete a 24 hour urine
  • Kidney ultrasound or CT scan
  • Eye examination (APRTd patients only)

Additional information that will be collected as part of this study:

  • Questionnaire completed by the patient about  kidney stones
  • Food frequency questionnaire (patients 8 years and older), or a three-day food diary (patients ages 0-7 years old) completed by the patient

Targeted Enrollment

 To be eligible to participate, you must:

  • Be willing to return annually for the next 5 years
  • Participate in the observational disease specific Registry Protocol (RKSC 6401)
  • Participate in the Biobank Protocol (RKSC 6404)
  • Participate in the Quality of Life Protocol (RKSC 6408), except for patients 0-5 years old
  • Be an individual with one of the following:
    • Diagnosis of PH
    • Diagnosis of EH
    • Diagnosis of Dent Disease
    • Diagnosis of Cystinuria
    • Diagnosis of APRTd
    • Diagnosis of Lowe Syndrome
    • Diagnosis of Dent Disease Carrier

You are not eligible to participate if you have:

  • Prior renal failure
  • History of liver and/or kidney transplant

How to participate

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

United States


Mayo Clinic Florida, Jacksonville
Contact: Arta Palaj
Phone: 904-953-9071
E-mail: palaj.arta@mayo.edu

New York

New York University School of Medicine, New York
Contact: Frank Modersitzki
Phone: 212-686-7500 Ext: 6379
E-mail: Frank.Modersitzki@nyumc.org


Mayo Clinic College of Medicine, Rochester
Study Coordinator: Barb Seide
Phone: 800-270-4637
E-mail: hyperoxaluriacenter@mayo.edu

Study Coordinator: Julie Olson, RN
Phone: 800-270-4637
E-mail: hyperoxaluriacenter@mayo.edu

Principal Investigator: John C. Lieske, MD


Landspitali – The National University Hospital of Iceland, Reykjavik
Contact: Dr. Vidar O. Edvardsson
Phone: +354-824-5227
E-mail: rarekidneystones@landspitali.is