© Borgis - Postępy Nauk Medycznych 5/2013, s. 351-356
*Jacek Płonka1, Halina Woś2, Lidia Hyla-Klekot3
Stężenie karnityny w surowicy krwi u dzieci z zespołem nerczycowym
Carnitine concentration levels in serum of children with nephrotic syndrome
1Pediatric Ward of the Regional Medical Centre, Opole
Head of Ward: Janusz Zaryczański, MD, PhD
2Pediatric Clinic of the Silesian Medical University, Katowice
Head of Clinic: prof. Halina Woś, MD, PhD
3Technical University in Opole, Department of Physiotherapy
Head od Department: prof. P.O. Krzysztof Wronecki, MD, PhD
Streszczenie
Wstęp. Karnityna jest czwartorzędową aminą biogenną, której kluczowa funkcja w organizmie polega na udziale w metabolizmie lipidów. Zaburzenia gospodarki lipidowej to jeden z głównych objawów zespołu nerczycowego u dzieci, które w przyszłości prowadzić mogą do zespołu metabolicznego. Nieliczne dotychczas badania zachowania się stężenia karnityny w zespołach nerczycowych u dzieci wskazują na zaburzenia dotyczące karnityny, ale ich wyniki są niespójne.
Celem pracy była ocena stężenia karnityny i jej frakcji w surowicy krwi u dzieci z zespołem nerczycowym, próba określenia zależności między zmianą stężenia karnityny i jej frakcji a parametrami gospodarki lipidowej i białkowej.
Materiał i metody. Badaniem objęto 37 dzieci w wieku od 17 miesięcy do 15 lat 8 miesięcy z rozpoznanym zespołem nerczycowym, u których oznaczono poziom karnityny i jej frakcji w surowicy, stężenie cholesterolu, trójglicerydów i białka całkowitego w surowicy krwi, w okresie ostrym i w okresie remisji zespołu nerczycowego.
Do oznaczenia w osoczu karnityny i jej pochodnych zastosowano metodę opracowaną przez Cederblata w modyfikacji Rösslera opartą na kombinowanym teście radio-enzymatycznym.
Wyniki. Średnie stężenie karnityny całkowitej w ostrym stanie ZN wynosiło 46,55 +/- 15,67 μmol/L, natomiast po ustąpieniu białkomoczu było niższe i wynosiło 40,72 +/- 10,9 μmol/L (p < 0,05). Również średnie stężenie karnityny wolnej w ostrym okresie choroby było wyższe niż w okresie zdrowienia: 38,09 +/- 13,53 vs 33,03 +/- 9,62. Podobne korelacje zachodziły w odniesieniu do karnityny zacylowanej oraz wskaźnika karnityny zacylowanej dowolnej. Zaburzenia gospodarki karnityną obserwowano u większości pacjentów.
Podsumowanie:
1. U dzieci z ZN występują zaburzenia w zakresie metabolizmu karnityny, wyrażające się bądź wysokim jej stężeniem, bądź niedoborem. Nie obserwuje się klinicznych cech niedoboru karnityny.
2. Wyższe wartości karnityny w ostrym okresie choroby mogą być związane ze stymulacyjnym wpływem hiperlipidemii na jej metabolizm.
3. Normalizacji parametrów gospodarki lipidowej i białkowej w okresie remisji zespołu nerczycowego towarzyszy spadek stężenia karnityny całkowitej, wolnej i zacylowanej.
4. Udział karnityny w złożonych zaburzeniach metabolicznych występujących w zespole nerczycowym wymaga dalszych analiz.
Summary
Introduction. Carnitine is a quaternary ammonium compound. Its key function in organism is based on taking an active part in lipids’ metabolism. Disorders appearing in lipid distribution are one of the main symptoms of nephrotic syndrome in children. In result, such disorders may later lead to metabolic syndrome. The recent, however not numerous, studies on carnitine levels and their behaviour in children suffering from nephritic syndrome, showed disorders concerning carnitine. Unfortunately, the results seem not to be very consistent.
Aim. The main objective of the study was to assess the concentration levels of carnitine and its fractions in serum of children with nephrotic syndrome and also take an attempt to determine the relationship between carnitine and its fractions levels change and the lipid and protein distribution parameters.
Material and methods. The subjects of the study were 37 children (the age range between 17 months and 15 years 8 months) who were all diagnosed with nephrotic syndrome. All these children had their carnitine and its fractions levels in serum determined as well as the concentration level of cholesterol, triglycerides and total protein. The tests were done in both, the acute period of nephrotic syndrome and in its remission phase.
The method used to determine carnitine and its fractions levels in serum was the one invented by Cederblat with its later modifications introduced by Rössler, and based on the radio-enzymatic combined test.
Results. Average carnitine concentration in the acute period of nephrotic syndrome was 46.55 +/- 15.65 μmol/L, however, after proteinuria remission it decreased and came to 40.72 +/- 10.9 μmol/L (statistically typical value). The average free carnitine concentration level observed in the acute period was also higher than in the remission period: 38.09 +/- 13.53 vs 33.03 +/- 9.62. Similar correlations were observed with regards to acyl-carnitine and free acyl-carnitine ratio. Carnitine distribution disorders were found in the majority of patients.
Conclusions:
1. Children with nephrotic syndrome show disorders of carnitine metabolism, expressed either in its high concentration or its deficiency. However, clinical features of carnitine deficiency have not been observed.
2. Higher levels of carnitine observed in the acute period of the disease can be associated with hyperlipidaemia’s stimulating influence on carnitine’s metabolism.
3. A normalization process of the lipid and protein distribution parameters in the remission period of the disease is accompanied by the decrease of concentration level of total carnitine as well as free and acyl-carnitine.
4. Carnitine’s participation and its role in complex metabolic disorders observed in nephrotic syndrome requires further studies and analyses.
Introduction
Nephrotic syndrome is a multidimensional disorder of body homeostasis induced by a loss of protein due to a destroyed nephrons’ filter membrane. In the light of recent studies, it has been found out that this phenomenon may have the acquired character and be the effect of the loss of balance between inhibitors and promoters of protein permeability through nephrons’ membrane or be the conseqence of a genetically determined, primary defect of this microstructure (1, 2). Nephrotic syndrome is the most frequently observed clinical form of children’s age glomerulopathy. Its chronic and recurrent character cause that incidence of its appearence in children’s population is estimated to reach the level of 16/100 000 (1).
Nephrotic syndrome, developing on the basis of minimal change of chronic glomerulonephritis and focal segmental glomerulosclerosis, appears to be one of the most difficult diagnostic and therapeutic problem found in children’s nephrology. The leading biochemical disorder in nephrotic syndrome is a loss of protein in the amount of 50 mg/kg/daily. Proteinuria results in dyslipidemia that has been observed in case of some patients even when proteinuria is in its remission stage. In spite of the fact that the lipid distribution disorder participation in nephrotic syndrome has been known for over 170 years, its exact pathomechanism is still unclear (3-5).
The lipid disorder found in nephrotic syndrome concerns all lipoprotein fractions, however the leading disorder is hypercholesterolemia and hypertriglyceridemia. HDL lipoprotein concentration may be decreased, increased or normal (5). Hyperlipidemia appearing in the course of nephrotic syndrome, is connected with a compensatory growth of protein synthesis, including apoprotein present in the liver, as the response to the loss of protein excreted with urine. Later, proteins combine with lipid elements of serum and create lipoproteins. Lipoprotein molecules are not excreted with urine and therefore their concentration in serum is above normal.
Hypercholesterolemia observed in nephrotic syndrome is the effect of an intensive cholesterol synthesis resulting from the increased activity of a key enzyme and its biosynthesis-reductase HMG-CoA, and also function disorder of other enzyms involved in lipid metabolism: lecithin-cholesterol acyltransferase (LCAT) and sterol O-acyltransferase acyl-CoA: cholesterol (ACAT). The latter one catalyzes the intracellular esterification of cholesterol and formation of cholesteryl esters in the cell. The intracellular estrification of cholesterol by ACAT leads to the decrease of free cholesterol in serum which activates the key enzyme cholesterologenesis-reductase HMG-CoA (4, 5). Hypertriglyceridemia appearing in nephrotic syndrome is caused by the increased VLDL synthesis in the liver and a defective lipoprotein catabolism, especially of a VLDL fraction. LDL molecules undergo direct synthesis in the liver through the alternative metabolic path.
Dyslipidemia appearing in nephrotic syndrome is a significant pathophysiological factor responsible for damaging nephrons. Receptors for lipoproteins have been found in mesangium as well as in podocytes. In nephrotic syndrome, lipoproteins are uncontrollably intercepted by mesangium cells and then they undergo a proliforation process. Lipoproteins accumulated in mensangium get oxidized and in this form they stimulate the process of antibodies creation. Complexes, i.e. an oxidized LDL antibody, are intercepted by macrophages which later undergo a transformation process in order to become foam cells which are the source of numerous mediators of the inflammatory condition. The effect of their activity is the further proliferation process of mensangium cells, increased adhesion of monocytes into endothelium cells, creation of inflammatory intumescences, monocytes apoptosis and in result, dysfunction of nephrones’ filtering membrane. The whole process is referred to as ateroglomerulosclerosis (7, 8). The lipid metabolism disorder in nephrotic syndrome constitutes a great risk factor of developing early atherosclerosis together with its clinical consequences, such as cardiovascular system related diseases.
The key function of carnitine as an essential nutricious substance, belonging to a group of natural elements possessed by all superior organisms is its active part in lipid metabolism, enabling transport of longchain fatty acids to mitochondrial matrix where they can undergo the process of β-oxidation. All the research, carried out in recent years, is trying to explain the role of carnitine in human organism and its significant role in lipid metabolism. Not numerous research concerning carnitine’s behaviour in serum of children suffering from nephrotic syndrome show disorders in concentration levels of total and free carnitine as well as its esters. Unfortunately, the results of the research are not consistent.
Aim of the study
The objective of the study is:
– to assess the concentration levels of carnitine and its fractions in serum of children with nephrotic syndrome,
– to take an attempt to determine the relationship between carnitine and its fractions levels change and the lipid and protein distribution parameters.
Patients and methods
The subjects of the study were 37 children at the age between 16 months old and 15.8 years old (average 4.8 years old) including 10 girls and 27 boys with a diagnosis of nephrotic syndrome. All these children had their carnitine and its fractions (total, free and acyl-carnitine) levels in serum determined as well as the concentration level of lipids (total cholesterol), triglycerides and total protein and the ratio of acyl-carnitine to free carnitine. The tests were done twice, in the acute period of nephrotic syndrome, i.e. when the children were taken to hospital (test 1) and in the disease remission phase, i.e. when proteinuria disappeared (test 2).
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