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

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 mu mol/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 mu mol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 mu mol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 mu mol/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 mu mol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 mu mol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 mu mol/L) with 250 and 500 mg, respectively (P < 0.001). The calcium oxalalte 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 mu mol) to 99.6 +/- 51.7 mg (566 +/- 294 femol) during supplementation (P < 0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 rng (917 - 369 mu mol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 mu mol; 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. Conclusion: 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.