Carnitine Supplementation in Pediatric Hemodialysis Patients

The goal of this study is: To determine the prevalence of carnitine deficiency among pediatric patients on hemodialysis. To evaluate the efficiency of carnitine supplementation in children on regular hemodialysis with carnitine deficiency in the treatment of renal anemia, cardiac dysfunction, dyslipidemia, intradialytic muscle cramps and hypotension and their quality of life.

Patients on hemodialysis (HD) often have carnitine deficiency due to multiple factors; dietary intake of carnitine is decreased due to falls in appetite, total energy levels, and protein intake. In addition, accumulating evidence has linked inflammation to malnutrition, and chronic inflammation might also interrupt carnitine transfer in the intestine. Carnitine biosynthesis can also fall in patients on dialysis due to reduced biosynthesis in the kidney and limited compensation by the liver. Furthermore, because of the low molecular weight of carnitine and its high hydrophilicity and absence of protein binding, carnitine is significantly removed by the dialyzer. As in the healthy population, carnitine deficiency in patients receiving maintenance dialysis is most commonly defined as a serum free carnitine level less than 20 μmol/L . Intravenous levocarnitine is commonly used to treat patients receiving maintenance hemodialysis who are diagnosed with carnitine deficiency since it has 100%bioavailability and does not break down into toxic metabolites. A common dose used for carnitine supplementation is 10-20 mg/kg administered after each hemodialysis session, which produces the supraphysiologic serum levels of carnitine that are required to adequately drive carnitine from the serum into skeletal muscles. There are four principal indications for levocarnitine treatment in dialysis patients with carnitine deficiency according to the American National Kidney Foundation: (1) erythropoiesis stimulating agents resistant anemia that has not responded to the standard erythropoiesis stimulating agent dosage; (2) recurrent symptomatic hypotension during hemodialysis;(3) symptomatic cardiomyopathy or confirmed cardiomyopathy with reduced left ventricular ejection fraction and(4) fatigability and muscle weakness that undermine the quality of life.

Enrolled patients in this group who are on regular hemodialysis fulfilling our study's inclusion criteria with secondary carnitine deficiency(based on clinical manifestations and decreased serum level of L-carnitine ;serum free carnitine level less than 20 μmol/L) will receive intravenous L-carnitine (20 mg/kg dry body weight) after each dialysis session three times weekly for 6 months.

enrolled patients in this group who will receive 5 ml intravenous isotonic saline after each dialysis session three times weekly for 6 months.

The investigator will measure hemoglobin level to assess effect of supplementation on renal anemia. and Erythropoietin dose

using (The Fresenius Medical Care Body Composition Monitor - BCM) to assess fat composition percentiles.

using (The Fresenius Medical Care Body Composition Monitor - BCM) to assess lean tissue index percentiles.

assessment of quality of life using 36 -item short form survey instrument (SF- 36) questionnaire, it is a perceived quality of life assessment tool which will be used to assess general health, physical functioning, bodily pain, and mental health with a scale 0 - 100 , The lower the score the more disability.

Inclusion Criteria: All patients on regular hemodialysis for more than three months with L-carnitine deficiency. Anemia (hemoglobin [Hb] < 11 g/dl; hematocrit [Hct] < 30%) resistant to erythropoietin defined as Anemia that require recombinant human erythropoietin (rHuEPO) doses >300 units/kg/week intravenously in spite of adequate iron stores (transferrin saturation >20%, ferritin >100 ng/mL), and without any other identifiable cause of anemia. Recurrent intradialytic complications (cramping, muscular pain, hypotension) Cardiomyopathy with reduced left ventricular ejection fraction. Sex: both males and females. Age: 16 years old or less. Exclusion criteria: Patients known to be allergic to L-carnitine. Patients with inborn error of metabolism. Patients on lipid lowering therapy. Patients with Diabetes mellitus. Patients with Associated congenital heart disease. Patients with Thyroid disorder, or malignancy. Patients received L-carnitine within the past 6 months. Patients received Blood transfusion 4 weeks prior to study.

Eknoyan G, Latos DL, Lindberg J; National Kidney Foundation Carnitine Consensus Conference. Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. National Kidney Foundation Carnitine Consensus Conference. Am J Kidney Dis. 2003 Apr;41(4):868-76. doi: 10.1016/s0272-6386(03)00110-0.

Evans A. Dialysis-related carnitine disorder and levocarnitine pharmacology. Am J Kidney Dis. 2003 Apr;41(4 Suppl 4):S13-26. doi: 10.1016/s0272-6386(03)00113-6.

KDOQI Work Group. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 update. Executive summary. Am J Kidney Dis. 2009 Mar;53(3 Suppl 2):S11-104. doi: 10.1053/j.ajkd.2008.11.017. No abstract available.