Clarify genetic causes

Expert-backed testing to diagnose and differentiate

While dehydration, certain medications, diet, and digestive disorders are common factors that can increase the risk for electrolyte imbalances and the development of kidney stones, genetic causes are also linked to stone development.  

Renal tubular loss of electrolytes or protein or the development of kidney calculi can signal underlying metabolic, endocrine, or renal tubular dysfunction that is genetic in origin, especially when symptoms are present in utero, infancy, or adolescence.

When the presence or severity of electrolyte imbalance or kidney stones cannot be explained by acquired causes or when there are multiple cases clustered within a family, genetic testing for the inherited causes of kidney or extrarenal impairment of osmoregulation may be considered.

Mayo Clinic Laboratories’ nephrocalcinosis, nephrolithiasis, and renal electrolyte imbalance gene panel assesses 72 genes associated with inherited conditions that can lead to stone development. Developed by a team of Mayo Clinic nephrologists and geneticists, our RSCGP testing panel uses next-generation sequencing to detect single nucleotide, deletion-insertion, and copy number variants in 72 genes associated with nephrocalcinosis, nephrolithiasis, and renal electrolyte imbalance.

Key testing

RSCGP | Nephrocalcinosis, Nephrolithiasis, and Renal Electrolyte Imbalance Gene Panel, Varies

  • Provides a genetic evaluation for patients with a personal or family history suggestive of a hereditary form of nephrocalcinosis, nephrolithiasis, or renal electrolyte imbalance.
  • Establishes diagnoses for a variety of hereditary conditions associated with renal salt wasting or abnormal salt retention; impaired acid-base, water, and calcium homeostasis; or kidney crystallization.
  • Variants classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
  • Detects both small variants, including single nucleotide variants and insertions and deletions, and copy number variants.
  • Validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. 
  • Provides standard coverage of +/-10 base pairs flanking each coding exon, along with expanded coverage to detect rare, clinically actionable, intronic genetic variants.

Distinguish between primary and secondary hyperoxaluria

Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity and is classified into types 1, 2, and 3. Increased urine concentrations of oxalate along with glycolate (type 1), glycerate (type 2), or 4-hydroxy-2-oxoglutarate (type 3), suggest a specific primary hyperoxaluria type. Follow-up genetic testing can confirm diagnosis.

Secondary hyperoxaluria is an acquired condition that is caused by an increased intake of dietary oxalate or altered intestinal oxalate absorption. With this condition, glycolate, glycerate, and 4-hydroxy-2- oxoglutarate (HOG) are not increased. When undiagnosed, these disorders can lead to recurrent renal stones, nephrocalcinosis, and often end-stage renal disease.

Experienced diagnostics for improved patient outcomes

Mayo Clinic Laboratories is integrated with the Hyperoxaluria Center at Mayo Clinic — one of the most experienced medical centers in the world for diagnosing patients who have primary and secondary hyperoxaluria. Mayo Clinic Laboratories hyperoxaluria panel can distinguish between the two forms of hyperoxaluria by quantifying excretion of oxalate, glycolate, glycerate and 4-hydroxy-2-oxoglutarate. The results of this assay are reported with interpretive comments and include recommendations for molecular testing.

Key testing

HYOX | Hyperoxaluria Panel, Random, Urine

  • Distinguishes primary from secondary hyperoxaluria.
  • Distinguishes between primary hyperoxaluria 1, 2, and 3.

When to consider testing

  • For patients who present with urinary stones or nephrocalcinosis in childhood.
  • To determine the etiology of recurrent calcium oxalate stones.
  • To guide appropriate use of definitive testing.
  • In patients with a family history of stone disease.

Learn more about how to order these evaluations at your institution.