Biobank Protocol, Rare Diseases Clinical Research Network


About this study

This study is being done to obtain samples from patients with primary hyperoxaluria, cystinuria, adenine phosphoribosyl transferase (APRT) deficiency, and Dent disease, and from their family members, for use in future research.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Diagnosis of primary hyperoxaluria:

  • Age > 0 AND at least one of the following criteria:
    • Liver biopsy documenting AGT activity below the normal reference range confirming PH1; OR
    • Liver biopsy documenting GR/HPR activity below the normal reference range confirming PH2;
    • Molecular genetic analysis (DNA testing) confirming a mutation known to cause PH 1, PH 2, PH 3; homozygosity or compound heterozygosity of mutations of AGXT, GRHPR, or HOGA 1 genes;
    • Urinary oxalate excretion of greater than 0.8 mmol/1.73 m2/day (?70 mg/1.73 m2/day) in the absence of a gastrointestinal disease known to cause hyperoxaluria (enteric hyperoxaluria);
    • If the patient presented in end stage renal failure, and neither a liver biopsy nor mutational analysis were obtained, 5a AND 5b must be fulfilled along with at least one of the criteria listed in 5c.:
      • Pre-dialysis plasma oxalate greater than 60 µmol/L; AND
      • Renal biopsy confirming extensive oxalate deposition; OR
      • Evidence of systemic oxalosis (at least one of the following criteria):
        • retinal oxalate deposits.
        • oxalate deposits in bone marrow, skin , or other tissue (histologically confirmed).
        • nephrocalcinosis.
        • calcium oxalate nephrolithiasis.
      • Have related, uncharacterized, disorder.
      • Participants in the previous protocol "Tissue Bank of Urine, Blood, and Tissue Samples Collected from the Patients with Primary Hyperoxaluria" Mayo IRB #80-04.  These participants have already consented to bank their samples and that consent will serve to enroll them in this study.  No new consent will be obtained.

Diagnostic Criteria for enteric hyperoxaluria:

  • Two or more 24 hour urine collections in the year prior to enrollment with oxalate > 0.6mmol/1.73m2 BSA/24 hours; and ONE or more of the following:
    • GI disease known to cause malabsorption;
    • History of malabsorptive bariatric surgical procedure;
    • History of small bowel resection sufficient to cause malabsorption.

Diagnosis of Cystinuria:

  • Stone analysis demonstrating that the stone contains cystine as a component;
  • Increased urinary cystine excretion (>250 mg/24 hours in adults and >250 mg/gm creatinine in children).

Diagnosis of Dent disease, Low Syndrome and Dent Carriers:

  • Age ≥ 0;
  • Documented LMWP > 5x the upper reference range at any time point; AND at least ONE of the following criteria:
    • Identified mutation of the CLCN5 gene (Dent 1) or the OCRL1 gene (Dent 2);
    • Hypercalciuria, nephrocalcinosis, or stones;
    • Hypophosphatemia or rickets;
    • Family history of stones, CKD or proteinuria.
  • Genetic testing will be done for all longitudinal cohort patients to classify as Dent 1 (CLCN5).  Lowe Syndrome or Dent 2 (OCRL1); or non 1/2 Dent (negative for both genes) and Dent Carriers.

Diagnosis of APRT disease:

  • Age > 0, diagnosis of APRT deficiency based on at least one of the following criteria:
    • Suspected dihydroxyadeninuria and abolished in vivo APRT enzyme activity;
    • Homozygosity, or compund heterozygosity, for known disease-causing APRT mutations with or without suspected dihydroxyadeninuria;
    • Homozygosity, or compund heterozygosity, for novel APRT mutations and abolished in vivo APRT enzyme activity, with or without suspected dihydroxyadeninuria;
    • Passage of dihydroxyadenine stones (confirmed with stone analysis), with or without suspected dihydroxyadeninuria, and abolished in vivo APRT enzyme activity or the presence of homozygosity, or compund heterozygosity, for disease-causing mutations;
    • Have related, uncharacterized, disorder.

Clinical Suspicion of a monogenic kidney stone disease:

  • Patients > 18 years old with a history of kidney stones, and/or nephrocalcinosis; OR
  • Patients > 18 years old with a history of kidney stones, and/or nephrocalcinosis and at least ONE of the following:
    • Family history of stones or nephrocalcinosis or unexplained kidney failure;
    • Growth retardation due to metabolic bone disease and/or renal failure;
    • Crystals of unusual type;
    • Mild-to-moderate proteinuria;
    • Elevated serum creatinine and/or reduced GFR;
    • Hypomagnesemia; OR
    • Increased urinary calcium excretion;
    • Increased urinary oxalate excretion;
    • Renal cysts.

Family member of a patient who meets any of the above inclusion criteria.

Exclusion Criteria:

  • Stone formers who do not meet the inclusion criteria for primary hyperoxaluria, cystinuria, Dent disease, or APRT deficiency.
  • Unwilling or unable to provide consent/assent.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

John Lieske, M.D.

Open for enrollment

Contact information:

Mayo Clinic Hyperoxaluria Center

(800) 270-4637

More information


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