title: Long-term, low-dose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients.
abstract: BACKGROUND
  Ascorbate supplementation for patients on regular dialysis treatment (RDT) is advised to obviate deficiency and improve epoetin response in those with functional iron deficiency. However, clear-cut safety concerns regarding hyperoxalemia are still poorly understood. This study tries to establish safety/efficacy profiles of ascorbate and oxalate during long-term intravenous ascorbate supplementation.
  
  
  METHODS
  A prospective study was performed in 30 patients on RDT showing ascorbate deficiency (plasma ascorbate < 2.6 mg/L [<15 micromol/L]): 18 patients were administered intravenous ascorbate during 18 months (250 mg/wk, subsequently increased to 500 mg), and 12 patients were taken as reference untreated cases. Plasma ascorbate and oxalate assays and dialytic balance determinations were performed (ion chromatography and reverse-phase high-performance liquid chromatography, respectively) at baseline, during treatment, and 12 months after withdrawal.
  
  
  RESULTS
  Plasma ascorbate levels increased dose dependently with supplementation (1.6 +/- 0.8 mg/L [9.1 +/- 4.6 mumol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 micromol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 micromol/L] with 500 mg/wk of ascorbate), but only normalized with greater dosages for several months in 94% of patients. Baseline plasma oxalate levels increased from 3.2 +/- 0.8 mg/L (35.8 +/- 8.8 micromol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 micromol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 micromol/L) with 250 and 500 mg, respectively ( P < 0.001). The calcium oxalate saturation threshold was exceeded by 7 of 18 patients (40%) during 6 months therapy with 500 mg/wk. Ascorbate dialysis removal increased from 37.8 +/- 23.2 mg (215 +/- 132 micromol) to 99.6 +/- 51.7 mg (566 +/- 294 micromol) during supplementation (P < 0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 mg (917 +/- 369 micromol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 micromol; P < 0.01). Withdrawal reverted plasma levels and dialysis removal to initial values. Values for untreated patients did not change during 1 year of follow-up.
  
  
  CONCLUSIONS
  Patients on RDT may resolve ascorbate deficiency with intravenous supplementation of 500 mg/wk, but this implies a significant risk for oxalate supersaturation. Oxalate measurements are strongly recommended during long-term ascorbate therapy.
authors.affiliation: Department of Nephro-Urology, Nephrology and Transplantation, Amedeo Avogadro University, Maggiore Hospital, Novara, Italy. ccanavese@hotmail.com
authors.forename: Caterina
authors.initials: C
authors.lastname: Canavese
authors.forename: Michele
authors.initials: M
authors.lastname: Petrarulo
authors.forename: Paola
authors.initials: P
authors.lastname: Massarenti
authors.forename: Silvia
authors.initials: S
authors.lastname: Berutti
authors.forename: Roberta
authors.initials: R
authors.lastname: Fenoglio
authors.forename: Daniela
authors.initials: D
authors.lastname: Pauletto
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lanfranco
authors.forename: Daniela
authors.initials: D
authors.lastname: Bergamo
authors.forename: Luisa
authors.initials: L
authors.lastname: Sandri
authors.forename: Martino
authors.initials: M
authors.lastname: Marangella
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000517:prevention & control; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001206:Ascorbic Acid Deficiency / Q000188:drug therapy / Q000209:etiology; D002129:Calcium Oxalate / Q000097:blood*; D004351:Drug Resistance; D004921:Erythropoietin / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006959:Hyperoxaluria / Q000139:chemically induced / Q000209:etiology; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis
chemical_list: D004921:Erythropoietin; D002129:Calcium Oxalate; D001205:Ascorbic Acid