Micronutrient deficiency in chronic kidney disease (Editorial)

The association between chronic kidney disease (CKD) and malnutrition is well-known and is usually considered in the context of reduced lean body mass and its consequences. Protein-calorie malnutrition develops prior to the need for renal replacement therapy. Reduced lean body mass is demonstrable in stage III CKD, and may be accompanied by spontaneous reductions in dietary protein intake, reduced energy expenditure and increased protein catabolism. Malnutrition is highly prevalent at the commencement of renal replacement therapy and is a powerful predictor of subsequent morbidity and mortality, which is largely attributable to an increase in cardiovascular events. The link between protein-calorie malnutrition and adverse clinical outcomes may be mediated by inflammatory changes which predispose both to malnutrition and atherogenesis. Additionally, endocrine abnormalities of CKD, such as the insulin resistance, may contribute both to protein catabolism and the accumulation of ‘traditional’ vascular risk factors which predispose to atherogenesis. These changes are compounded by dialysis which is associated with muscle catabolism, somatic-visceral recycling of amino acids and increased loss of amino acids in dialysate. Increased oxidative stress associated with dialysis contributes to the generation of oxidized atherogenic lipoproteins which accelerate vascular damage and may result in direct endothelial toxicity. Two articles in this edition of Nephrology highlight another aspect of nutrition – micronutrient deficiency – which also has a significant impact on clinical outcomes in dialysis patients. Deficiency of micronutrients may arise because of reductions in dietary intake, increased clearance by dialysis or because of alterations in renal metabolism occurring as a consequence of declining renal function. Increased clearance of water soluble vitamins by dialysis is well described. The potential consequences of deficiency of these vitamin groups include impaired wound healing and immunity, reductions in plasma antioxidant activity and haematological and neuropathic changes. These observations have resulted in the recommendation to routinely supplement water soluble vitamins in dialysis patients. In this issue of Nephrology, Singer et al. highlight the ongoing relevance of this aspect of management. In a group of peritoneal dialysis patients who had received appropriate initial advice about vitamin supplementation, a high prevalence of ascorbate deficiency (one-third of the total study group) was documented. This finding contrasts with other reports, principally in haemodialysis patients, in which near normal levels of ascorbate have been reported. Interestingly, in the population reported by Singer, while ascorbate deficiency was most common in patients not taking an ascorbate supplement, a significant proportion of patients taking an ascorbate-containing supplement were also deficient. Reuter et al. highlight alterations in carnitine kinetics which reflect complex interactions between reduced dietary intake, altered renal metabolism and increased clearance by dialysis. Carnitine is a low molecular weight molecule which plays a key role in mitochondrial fatty acid transport and regulation of free fatty acid b-oxidation. It therefore plays a critical role in tissues such as skeletal and cardiac muscle which use b-oxidation for energy requirements and is thought to play a role in plasma fatty acid metabolism and phospholipid stabilization in cell membranes. Reuter et al. summarize the evidence that L-carnitine deficiency is common in dialysis patients and describe the associated constellation of syndromes such as erythropoietin-resistant anaemia, intradialytic hypotension and dyslipidaemia which may be attributable to L-carnitine deficiency. The clinical manifestations of both ascorbate and L-carnitine deficiency and non-specific, and may be easily overlooked in the complex symptomatology of CKD. Both groups of investigators highlight the importance of routine measurement of these parameters as the most effective means of detecting deficiency. Once deficiency is detected, both micronutrients can be simply and effectively supplemented with relatively little risk of clinically significant toxicity at physiological levels of supplementation. However, the therapeutic dilemma for nephrologists is whether there is a demonstrable benefit to be obtained from supplementation and to what extent such supplementation should occur. The case for maintaining physiological plasma concentrations of ascorbate can be fairly easily made, given the well-known clinical consequences of ascorbate deficiency, which include dermatological changes, impaired wound healing and in extreme cases, scurvy. As Singer et al. argue, supplementation to achieve physiological levels of ascorbate should be associated with relatively little risk of toxicity. Ascorbate also has antioxidant activity which may confer additional benefit in reversing changes in endothelial function because of oxidative stress. However, the doses reported to achieve this antioxidant benefit (in patient subgroups other than CKD) are substantially greater than physiological replacement doses. In CKD, it remains unclear whether these benefits occur when ascorbate is supplemented above the physiological range. Such a treatment strategy would need to be balanced against the NEPHROLOGY 2008; 13, 1–2 doi:10.1111/j.1440-1797.2007. 00908.x