Long-term, low-dose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients

Abstract

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. 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. 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. 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.