The use of levo-carnitine in children with renal disease: a review and a call for future studies

Abstract

Carnitine is an amino acid derivative that has a key role in the regulation of fatty acid metabolism and ATP formation. Carnitine deficiency has been described in various conditions, including chronic kidney disease (CKD) and end stage renal disease (ESRD). The deficiency of this micronutrient is postulated to lead to adverse effects across multiple organ systems. There is a paucity of information on carnitine deficiency and its effects in the pediatric CKD and ESRD populations. Currently, there is no evidence supporting the routine use of carnitine supplementation in children with ESRD. In this article, we review the pathophysiology, pharmacokinetics and the potential effects of levo-carnitine supplementation with a focus on the pediatric CKD and ESRD populations. Finally, potential future directions of research are discussed.

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis

“…Other authors used higher dosages of L-carnitine in pediatric patients (see Table 4), but these were not associated with higher plasma FC levels or better clinical effects in short-term trials [10,11]. The 3-month observation period used in the present study seemed to be appropriate to evaluate FC levels, as these are known to increase during the first 2 months and to stabilize thereafter [3,9,19]. But normalized FC levels may not reflect normalized tissue carnitine stores.…”

“…Pediatric studies are even more rare than adult studies and were performed in a rather small number of patients on HD and/or PD treatment [9]. The effect of L-carnitine supplementation on serum lipid abnormalities was evaluated by Warady et al, who failed to show any benefit of L-carnitine supplementation on serum TG levels in six children on continuous ambulatory PD (CAPD) despite a significant increase in plasma total carnitine concentration [10].…”

“…However, a longer treatment time might be required to confirm or contradict these results. At present, it is wise to restrict carnitine supplementation to subgroups of children with carnitine deficiency and rhEPO-resistant anemia and/or skeletal muscle or cardiovascular dysfunction [9]. The determination of plasma FC levels seems to be helpful for the diagnosis of this condition and to monitor carnitine substitution.…”

“…As recently reported by Belay et al [9] in their review on the use of L-carnitine in children with renal disease, several studies have tested the effects of carnitine supplementation on serum lipid profile [10,11], erythropoietin (rhEPO) requirement [12], or nutritional status [13,14] in pediatric patients on chronic dialysis. As with reports in the adult population, these studies also generated inconsistent results.…”

Nonesterified Fatty Acids and Cardiovascular Mortality in Elderly Men with CKD

“…The heart toxicity of NEFA has been demonstrated to cause abnormalities in mitochondrial function (which may further impair myocardial function), and leads to damage in plasma membranes, including disturbances of the cardiomyocytes' ion channels (2), which have been considered to exert proarrhythmic effects (36)(37)(38). Finally, levocarnitine deficiency often appears with progressive kidney dysfunction (39,40) and has been suggested to affect cardiac function in this patient population (41). Interestingly, levocarnitine plays a crucial role in counteracting the toxic effect of NEFA (42), and we speculate that alterations at this level may, at least in part, provide an additional link between NEFA and CVD risk in patients with CKD that warrants further investigation.…”