Clinical Information

Dehydration, certain medications, diet, and digestive disorders are common factors that can increase the risk for electrolyte imbalances or the development of kidney stones. However, renal tubular loss of electrolytes or protein, or the development of kidney calculi can also signal underlying metabolic, endocrine, or renal tubular dysfunction that is genetic in origin, especially when symptoms present in utero, infancy, or adolescence.

When the presence or severity of electrolyte imbalance or kidney stones observed in a patient cannot be explained by acquired causes or there are multiple cases clustered within a family, genetic testing for the inherited causes of kidney or extrarenal impairment of osmoregulation may be considered. This gene panel assesses 72 genes associated with heritable causes of electrolyte imbalance and kidney stones. A thorough clinical and laboratory evaluation prior to genetic testing is often essential for correct genetic diagnosis. While many symptoms associated with kidney stone formation and/or electrolyte imbalance may overlap, most disorders are identifiable by distinct clinical features and a biochemical "signature" established by plasma electrolyte profiles, blood volume status, urine biochemistries, and kidney stone analysis.

Genes on this panel are associated with disorders of:

1) Renal salt wasting (Gitelman and Bartter syndromes, pseudohypoaldosteronism type 1, congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency, and glucocorticoid remediable aldosteronism)

2) Salt retention (pseudohypoaldosteronism type 2, Liddle syndrome, familial hyperaldosteronism types 1 and 3)

3) Acid-base homeostasis (proximal or distal renal tubular acidosis)

4) Water handling (nephrogenic diabetes insipidus, neurohypophyseal diabetes insipidus, and nephrogenic syndrome of inappropriate antidiuresis)

5) Calcium homeostasis (familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia), parathyroid function, and vitamin D metabolism

6) Kidney crystallization inhibitors, such as magnesium, uromodulin, and pyrophosphate

7) Kidney crystallization promoters such as oxalate (calcium oxalate nephrolithiasis), phosphate (hypophosphatasia, Dent disease, familial tumoral calcinosis), urate (Lesch-Nyhan syndrome, xanthinuria), cystine (cystinuria), and 2,8-dihydroxyadenine (adenine phosphoribosyltransferase deficiency)

This panel also includes genes associated with 3 syndromic disorders for which kidney stones or involvement have been reported: Wilson disease (low-molecular weight proteinuria, microscopic hematuria, and Fanconi syndrome that can result in kidney failure); amelogenesis imperfecta, type IG ("enamel-renal syndrome"; nephrocalcinosis); and Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young (MODY; nephrocalcinosis).