Rare Kidney Stones Consoritum

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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:

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

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), cystinuria, adenine phosphoribosyltransferase (APRT) deficiency, and Dent disease are rare inherited (genetic) disorders. These disorders 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.

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. ys stop working, oxalate accumulation in the body can cause damage to eyes, bones, muscles, heart and other major organs.


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.

APRT Deficiency

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

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

About this Study

Researchers hope to be able to understand the characteristics of these four 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 730 patients over five years. 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 5 years of the study.

Targeted Enrollment

Who is eligible to participate?

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 (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.

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)

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:
    • Crystals of 2,8-DHA (dihydroxyadenine) in the urine.
    • Genetic (DNA) testing showing pathogenic homozygous or compound heterozygous mutations of the APRT gene OR
    • Low or no APRT enzyme activity as measured in red blood cells obtained from a blood test
    • Stone analysis to confirm a stone made up of DHA OR
    • Kidney biopsy showing DHA crystals

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

  • 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


    All three of the following:
    • Low molecular weight protein in the urine (at least 5 times above the upper limit of normal).
    • High levels of calcium in the urine (> 4 mg (0.1 mmol)/kg in 24 hours or >0.25 mgCa2+/ mg Cr (0.57 mmol/mmol) in spot urine).
    • At least one of the following: nephrocalcinosis (deposits of calcium in the kidneys), kidney stones, hematuria (blood in the urine), hypophosphatemia (low levels of phosphorous in the blood) or renal insufficiency (loss of kidney function).

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

    Ross P. Holmes, PhD
    Professor of Urology
    Phone: 205-996-2291
    Email: rholmes@uab.edu

    Dean Assimos, MD
    Professor of Urology
    Phone: 205-934-4934
    Email: deanassimos@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


  • Mayo Clinic College of Medicine
    Contact: Tammy Evans
    Phone: (507) 284-1004
    E-mail: Evans.Tamara@mayo.edu

New York

  • New York University Medical Center
    Contact: Frank Modereski
    Phone: (212) 686-7500 Ext: 6379
    E-mail: Frank.Modersitzki@va.gov


  • The Children's Hospital of Philadelphia, Philadelphia
    Division of Nephrology
    Kathryn Malone
    Phone: 267-425-3940
    E-mail: malonek@email.chop.edu



  • Shaare Zedek Medical Center, Jerusalem

    PI: Dr. Yaacov Frishberg
    Phone: 972-2-6666144

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.