6401: Hereditary Causes of Nephrolithiasis (Kidney stones) and Kidney Failure

Status: Recruiting


For patients with kidney stones or kidney disease caused by any one of the following rare conditions:

  • Adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadeninuria
  • Cystinuria
  • Dent disease
  • Enteric hyperoxaluria (EH)
  • Lowe Syndrome
  • Primary hyperoxaluria (PH)

The goal of the study is to understand these diseases in order to develop new treatments to reduce both kidney stone formation and kidney damage.


Primary hyperoxaluria (PH), enteric hyperoxuria (EH), cystinuria, adenine phosphoribosyltransferase (APRT) deficiency, and Dent disease are rare inherited (genetic) disorders that are associated with kidney stone formation and kidney damage. The Rare Kidney Stone Consortium is studying these disorders to better understand how they affect patients. The overall goal of these studies is to develop new treatments to reduce kidney stone formation and the risk of kidney damage.

APRT Deficiency

APRT deficiency is a disorder that causes kidney stones, and chronic kidney disease leading to kidney failure in some cases. The stones are made up of 2,8 dihydroxyadenine (DHA), and can be confused with uric acid. This disease is also referred to as dihydroxyadeninuria.


Cystinuria is a disorder in which the kidney handles (transports) cystine in an abnormal way causing too much of it to enter the urine. Cystine is an amino acid (a building block of protein) that does not dissolve well in urine. When large amounts are found in the urine, cystine stones can form. Patients often have many stones requiring surgeries for their removal. Some suffer kidney damage as a result.

Dent disease

Dent disease (sometimes called Dent’s disease) affects the kidneys of males. Mild kidney changes are sometimes also found in women who are carriers for the disease. Patients with Dent disease often have:

  • Spillage of small proteins into the urine
  • High levels of calcium in the urine (hypercalciuria)
  • Low levels of phosphorous in the blood (hypophosphatemia)
  • Deposits of calcium in the kidneys (nephrocalcinosis)
  • Weak bones (osteomalacia)
  • Kidney failure

Primary Hyperoxalurias (PH)

Primary hyperoxaluria (PH) is a condition in which too much of a substance called oxalate is produced by the liver and then removed from the body in the urine. When too much oxalate is present in the urine, kidney stones or kidney deposits called nephrocalcinosis can form. PH is present at birth, but can go undetected for many years. Often the first symptom is pain, blood in the urine, or infection caused by kidney stones. Damage caused by the oxalate can eventually cause the kidneys to shut down. If the kidneys stop working, oxalate build up in the body can also cause damage to eyes, bones, muscles, heart and other major organs.

About this Study

Researchers hope to be able to understand the characteristics of these six disorders and their natural progression in order to develop effective treatments. In this study, researchers at several medical centers will collect clinical information from medical records on participating patient volunteers.

The goal is to enroll 1200 patients. Each patient who enrolls will give permission for researchers to review their medical records and to enter some of their health information into a database. In the database, a code number will be used to identify participants. Each patient’s progress will then be tracked by reviewing medical records at least once each year for up to the 10 years of the study.

Targeted Enrollment

Who is eligible to participate?

APRT Deficiency:

Patients of any age are eligible for this study if they:

  • Have a diagnosis of APRT deficiency based on one of the following criteria:
    • Have had a blood test to document absent APRT enzyme activity in red blood cells OR
    • Have had genetic analysis (DNA testing) to confirm a change in DNA (sequence variant) known to cause the disorder.

Patients of any age are eligible for this study if they:

  • Have had stone analysis demonstrating that the stone contains cystine as a component OR
  • Have increased urinary cystine in the urine (>250 mg/24 hours in adults and > 250 mg/gm creatinine in children)
Dent Disease:

Patients of any age are eligible for this study if they:

  • Have low molecular weight protein in the urine (at least 5 times above the upper limit of normal) AND at least two of the following criteria
    • High levels of calcium in the urine (> 4 mg (0.1mmol)/kg in 24 hours or > 0.25 mg Ca2+/mg Cr (0.57 mmol/mmol) in spot urine).
    • Nephrocalcinosis (deposits of calcium in the kidneys), kidney stones, hematuria (blood in the urine), hypophosphatemia (low levels of phosphorus in the blood) or renal insufficiency (loss of kidney function).


  • Have a diagnosis of Dent disease based on one of the following criteria:
    • Genetic (DNA) testing showing changes (mutation) in either the CLCN5 or OCRL1 gene
Primary Hyperoxaluria:

Patients of any age are eligible for this study if they:

  • Have large amounts of oxalate in the urine (usually at least twice as much as normal) and have no gastrointestinal disease known to cause hyperoxaluria (that is, they do not have enteric hyperoxaluria)
  • Have had genetic analysis (DNA testing) to confirm a change in DNA (mutation) known to cause one of the types of primary hyperoxaluria – type I (PH1), type 2 (PH2), or type 3 (PH3).
  • Have had a liver biopsy to document if either of the following types of enzyme activity below the normal range:
    • Alanine glyoxylate aminotransferase (AGT) (confirming PH1) OR
    • Glyoxylate reductase (GR) or hydroxpyruvate reductase (HPR) (confirming PH2).
  • Are in kidney failure, and have not had a liver biopsy or DNA testing but also have very high blood oxalate levels and evidence of oxalate deposits in body tissues.

You are not eligible to participate if:

  • You do not meet the conditions for participation for one of the four disorders described above.
  • You are unwilling or unable to provide consent. (Informed consent by participant or parent/legal guardian of minor participants will be required for all participants).
  • You are unwilling or unable to provide medical record information.


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


  • University of Alabama at Birmingham
    Contact: Ralee’ Bishop Bunt
    Phone: 205-934-2272
    E-mail: erikabunt@uabmc.edu



  • Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago
    Contact: Heather E. Price, M.S.
    Phone: 773-755-6368
    E-mail: hprice@luriechildrens.org


New York


  • The Children's Hospital of Philadelphia, Philadelphia
    Contact: Taylor Moatz
    Phone: 215-425-3937
    E-mail: MoatzT@email.chop.edu




  • Shaare Zedek Medical Center, Jerusalem, Israel
    Contact: Vardit Peles
    Phone: 972-7-72245355
    E-mail: varditpe@szmc.org.il

Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.