NDT Advance Access originally published online on November 19, 2007
Nephrology Dialysis Transplantation 2008 23(4):1463-1464; doi:10.1093/ndt/gfm819
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Think of oxalate when using ascorbate supplementation to optimize iron therapy in dialysis patients
E-mail: strattanefro{at}hotmail.comSir,
In a useful Primer on Iron Therapy recently published [1], there is an important point that should be clarified, to avoid misleading messages for the readers.
The authors wrote that supplementation of vitamin C (200 mg per day orally or 300–500 mg intravenously after each haemodialysis session) may result in the release of iron from the reticuloendothelial system, and thereby improve hyporesponsiveness to ESA (erythropoiesis-stimulating agents) [1], with a reference to a short-time clinical study that did not fully address monitoring for a possible oxalate overload [2].
Any suggestion to use ascorbate supplementation to optimize iron therapy in dialysis patients cannot fail to mention the relationship between ascorbate and oxalate.
There is no doubt that ascorbate supplementation will increase oxalate overload in uraemic people. Controversies still exist on the clinical meaning of such an increase, but some key points have been clearly established [3,4].
- (1) The threshold of plasma saturation for oxalate corresponds to
50 µmol/L [3].
- (2) Ascorbate supplementation in dialysis patients may increase oxalate plasma levels above this threshold.
- (3) Oxalate plasma levels showed a significant positive correlation with levels of ascorbic acid.
- (4) The threshold of plasma saturation may be exceeded with a dosage of ascorbate as low as 100 mg three times a week, infused intravenously after each dialysis session in 40% of patients during 6-month therapy with 500 mg/week [4].
- (5) A 5-fold increase in oxalate levels in the bone tissue of uraemic patients on regular dialysis has been demonstrated, even in the presence of undersaturated serum [3].
- (2) Ascorbate supplementation in dialysis patients may increase oxalate plasma levels above this threshold.
In conclusion, serum oxalate rises in uraemia because of decreased renal clearance, and crystals of calcium oxalate occur in the tissues of uraemic patients because uraemic serum is supersaturated with calcium oxalate. The possibility that hyperoxalaemia confers an increased risk of cardiac and vascular disease, even in the absence of primary hyperoxaluria, is debated and unknown, but presumably protective substances have been hypothesized to help in preventing the risk of systemic oxalosis despite increased plasma oxalate levels often to supersaturation levels, as oxalate deposition and systemic oxalosis are uncommon in patients with chronic renal failure, as opposed to patients with primary hyperoxaluria. Furthermore, a low total vitamin C plasma level is a risk factor for cardiovascular morbidity and mortality in haemodialysis patients [5] and therefore adequate supplementation is needed.
Nonetheless, the readers of the Primer should not believe that a dosage of ascorbate as high as 500 mg per 3 weeks in uraemic patients on chronic dialysis is definitely safe, as this is not the case.
Ascorbate, as is the case with iron therapy, cannot be scotomized to optimize erythropoietin therapy without looking at possible side effects.
Conflict of interest statement. None declared.
1 Departments of Clinical and Experimental Medicine, Nephrology and Transplantation & International Research Center Autoimmune Diseases (IRCAD) Italy 2 Renal Care Units of Mauriziano Hospital, Centro Calcolosi, Italy
References
- Schaefer L, Schaefer RM. A primer on iron therapy. Nephrol Dial Transplant (2007) 2:2429–2431.
- Keven K, Kutlay S, Nergizogly G, et al. Randomized, crossover study of the effect of vitamin C on EPO response in hemodialysis patients. Am J Kidney Dis (2003) 41:1233–1239.[CrossRef][Web of Science][Medline]
- Marangella M, Vitale C, Petrarulo M, et al. Bony content of oxalate in patients with primary hyperoxaluria or oxalosis-unrelated renal failure. Kidney Int (1995) 48:182–187.[Web of Science][Medline]
- Canavese C, Petrarulo M, Massarenti P, et al. Long-term, low-dose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients. Am J Kidney Dis (2005) 45:540–549.[CrossRef][Web of Science][Medline]
- Deicher R, Ziai F, Bieglmayer C, et al. Low total vitamin C plasma level is a risk factor for cardiovascular morbidity and mortality in hemodialysis patients. J Am Soc Nephrol (2005) 16:1811–1818.
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