Carnitine Replacement in End‐Stage Renal Disease and Hemodialysis

Abstract

In patients with chronic renal failure, not yet undergoing hemodialysis (HD), plasma acylcarnitines accumulate in part due to a decreased renal clearance of esterified carnitine moieties. In these patients, a high acylcarnitine/free-carnitine ratio is usually found in plasma. Patients undergoing maintenance HD, usually present with plasma carnitine insufficiency, due to accumulation of metabolic intermediates combined with impaired carnitine biosynthesis, reduced protein intake and increased removal via HD. Plasma carnitine concentrations rapidly decrease to 40% of baseline level during the dialysis session, with a slow restoration of the carnitine concentration during the interdialytic period, mainly from organs of storage (skeletal muscle). Dietary intake also plays an important role in carnitine homeostasis of HD patients since the prevalence of malnutrition ranges from 18% to 75% of these cases. This could differentially affect various body compartments, with clinical consequences such as impaired muscle function, decreased wound healing, altered ventilatory response, and abnormal immune function. Repeated hemodialytic treatments are associated with decreased carnitine stores in skeletal muscle. The administration of intravenous L-carnitine (LC) postdialysis replenishes the free carnitine removed from the blood and contributes to replenishment of muscle carnitine content. LC supplementation in selected uremic patients may yield clinical benefits by ameliorating several conditions, such as erythropoietin-resistant anemia, decreased cardiac performance, intradialytic hypotension, muscle symptoms, as well as impaired exercise and functional capacities. Furthermore, LC may positively influence the nutritional status of HD patients by promoting a positive protein balance, and by reducing insulin resistance and chronic inflammation, possibly through an effect on leptin resistance.

Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension

“…The levels of acylcarnitines are increased in plasma of patients with several inherited metabolic diseases. In these cases, the endogenous pool of carnitine becomes insufficient to cope with the required acyl transfer, and the plasma AC/FC ratio increases (10). The increase in AC/FC ratio reflects changes in the intramitochondrial equilibrium between acylCoA and free CoA (7,12).…”

“…CrAT plays an important role in maintaining carnitine metabolism (10). Therefore, we next determined total carnitine and free carnitine levels in the peripheral lung of shunt and control lambs.…”

The Effects of L-Carnitine Therapy on Respiratory Function Tests in Chronic Hemodialysis Patients

“…Furthermore, LC may reduce insulin resistance and chronic inflammation. [11] We have previously found that CRP levels may decrease by LC treatment. Additionally, there was a significant benefit of LC on transferrin, total protein, and albumin levels of the hemodialysis patients.…”

Diastolic Dysfunction and Pulmonary Hypertension in Sickle Cell Anemia: Is There a Role for <i>L</i>-Carnitine Treatment?

“…This could be explained by the stabilizing effect of L -carnitine on the erythrocyte membrane and by improvement in physical fitness secondary to the improved skeletal muscle metabolism with a subsequent decrease in blood transfusion requirement [41]. Moreover, the decrease in blood requirements could be secondary to increased responsiveness to erythropoietin which has been attributed to the effect of L -carnitine on erythropoietin-resistant anemia in hemodialysis patients [42]. Unfortunately, fetal hemoglobin or hemolysis markers (which might have shed some light on the mechanism involved in this decrease in need for transfusions) were not assessed at the end of the trial as this was not within the scope of this study.…”