title: Early effect of NTBC on renal tubular dysfunction in hereditary tyrosinemia type 1.
abstract: BACKGROUND
  Hereditary tyrosinemia type 1 (HT1) is characterized by severe progressive liver disease and renal tubular dysfunction. NTBC therapy has revolutionized the management of HT1 but its effect on renal tubular function has so far been poorly investigated. The aim of this study was to describe the early effect of NTBC on renal tubular disease in patients with HT1.
  
  
  METHODS
  Five HT1 patients (age between 5 and 53 months) with different types of presentation were evaluated before and during the first 2 weeks of therapy with NTBC in a retrospective case analysis for phosphate metabolism and renal tubular function.
  
  
  RESULTS
  Before starting NTBC therapy, all children manifested signs of renal dysfunction which included hypophosphatemia, acidosis, reduced phosphate reabsorption, aminoaciduria, glycosuria (Fanconi syndrome), and variable degree of proteinuria. Some patients also presented increased urinary calcium/creatinine ratio and raised fractional excretion of sodium. Starting of NTBC therapy resulted in the rapid normalization of plasma phosphate within one week from its initiation in majority of patients and in all patients during the second week of therapy. TmP/GFR normalized in 48h, while the other markers of renal dysfunction showed an improving trend over 2 weeks.
  
  
  CONCLUSIONS
  NTBC is an efficient treatment for renal tubular dysfunction in HT1, allowing the return to normal function within a few weeks. Its early effect on renal tubular cells appeared to be very rapid, particularly in normalizing plasma phosphate and TmP/GFR. In our series of patients, the TmP/GFR resulted as the most reliable index of tubular function.
authors.affiliation: Department of Pediatric Medicine, Division of Metabolism and Research Unit of Metabolic Biochemistry. Electronic address: arianna.maiorana@opbg.net.
authors.forename: A
authors.initials: A
authors.lastname: Maiorana
authors.affiliation: Department of Pediatric Medicine, Division of Metabolism and Research Unit of Metabolic Biochemistry. Electronic address: monicamalamisura@libero.it.
authors.forename: M
authors.initials: M
authors.lastname: Malamisura
authors.affiliation: Department of Nephrology & Urology, Division of Nephrology and Dialysis. Electronic address: francesco.emma@opbg.net.
authors.forename: F
authors.initials: F
authors.lastname: Emma
authors.affiliation: Department of Pediatric Medicine, Division of Metabolism and Research Unit of Metabolic Biochemistry. Electronic address: sara.boenzi@opbg.net.
authors.forename: S
authors.initials: S
authors.lastname: Boenzi
authors.affiliation: Department of Health, Unit of Epidemiology, Bambino Gesù Children's Hospital and Research Institute, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: vmaria.diciommo@opbg.net.
authors.forename: V M
authors.initials: VM
authors.lastname: Di Ciommo
authors.affiliation: Department of Pediatric Medicine, Division of Metabolism and Research Unit of Metabolic Biochemistry. Electronic address: carlo.dionisivici@opbg.net.
authors.forename: C
authors.initials: C
authors.lastname: Dionisi-Vici
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D002675:Child, Preschool; D003512:Cyclohexanones / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D007684:Kidney Tubules / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009579:Nitrobenzoates / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D020176:Tyrosinemias / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D003512:Cyclohexanones; D009579:Nitrobenzoates; C077073:nitisinone
keywords: Hereditary tyrosinemia type 1; NTBC; Phosphate homeostasis; Renal tubular dysfunction; Rickets; TmP/GFR