title: Renal phosphate handling in Gitelman syndrome--the results of a case-control study.
abstract: BACKGROUND
  Patients with Gitelman syndrome, a hereditary salt-wasting tubulopathy, have loss-of-function mutations in the SLC12A3 gene coding for the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. Since the bulk of filtered phosphate is reabsorbed in the proximal tubule, renal phosphate wasting is considered exceptional in Gitelman syndrome.
  
  
  METHODS
  We investigated the renal handling of inorganic phosphate in 12 unselected Italian patients affected with Gitelman syndrome (5 females and 7 males, aged 6.0-18 years, median age 12 years) and in 12 healthy subjects matched for gender and age (controls). The diagnosis of Gitelman syndrome among the patients had been made clinically and confirmed by molecular biology studies.
  
  
  RESULTS
  The biochemical hallmarks of Gitelman syndrome, namely hypochloremia, hypokalemia, hypomagnesemia, increased urinary excretion of sodium, chloride, potassium and magnesium and reduced urinary excretion of calcium, were present in the 12 patients. In addition, both the plasma inorganic phosphate concentration (median and interquartile range: 1.28 [1.12-1.36] vs. 1.61 [1.51-1.66)] mmol/L) and the maximal tubular reabsorption of inorganic phosphate (1.08 [0.99-1.22] vs. 1.41 [1.38-1.47] mmol/L) were significantly lower (P < 0.001) in Gitelman patients than in control subjects. Circulating levels of 25-hydroxyvitamin D, intact parathyroid hormone and osteocalcin were similar in patients and controls.
  
  
  CONCLUSIONS
  The results of our case-control study disclose a hitherto unrecognized tendency towards renal phosphate wasting with mild to moderate hypophosphatemia in Gitelman syndrome.
authors.affiliation: Division of Orthopedics, San Leopoldo Mandic Hospital, Merate, Lecco, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Viganò
authors.forename: Chiara
authors.initials: C
authors.lastname: Amoruso
authors.forename: Francesco
authors.initials: F
authors.lastname: Barretta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Minnici
authors.forename: Walter
authors.initials: W
authors.lastname: Albisetti
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Syrèn
authors.forename: Mario G
authors.initials: MG
authors.lastname: Bianchetti
authors.forename: Alberto
authors.initials: A
authors.lastname: Bettinelli
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D005260:Female; D053579:Gitelman Syndrome / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D011955:Receptors, Drug / Q000235:genetics; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics
chemical_list: D010710:Phosphates; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters