Lipoprotein(a) in chronic renal failure

JMB 2009; 28 (2) DOI: 10.2478/v10011-009-0004-0 UDK 577.1 : 61 ISSN 1452-8258 JMB 28: 82–88, 2009 Original paper Originalni nau~ni rad LIPOPROTEIN(a) IN CHRONIC RENAL FAILURE LIPOPROTEIN(a) U HRONI^NOJ BUBRE@NOJ INSUFICIJENCIJI Velibor ^abarkapa1, Mirjana \eri}1, Zoran Sto{i}1, Vladimir Saka~2, Sun~ica Koji}-Damjanov1, Nevena Eremi}1 1Center for Laboratory Medicine, Clinical Center of Vojvodina, Novi Sad, Serbia 2Clinic of Nephrology and Immunology, Clinical Center of Vojvodina, Novi Sad, Serbia Summary: Cardiovascular diseases are the leading cause of mortality in patients with chronic renal failure. Among the parameters contributing to cardiovascular disease development is the elevated serum concentration of lipoprotein(a) diagnosed in these patients, especially in the terminal stage of CRF. However, an elevated concentration of lipoprotein(a) could influence the renal failure progression. The objective of this study is to examine the lipoprotein(a) serum levels in chronic renal failure, and to establish the relation between the stage of renal function preservation and the level of this lipoprotein. In this study 127 subjects were included, divided into three groups. The first group contained 42 subjects (15 females and 27 males) in different CRF stages, the second group contained 32 subjects (7 females and 25 males) on a chronic hemodialysis program, and the control group contained 53 subjects (22 females and 31 males) with regular renal function. The results obtained point to significantly higher frequency of hyper-Lp(a) lipoproteinaemia in dialysed patients compared to the control group, as well as significantly higher Lp(a) values in both groups of patients compared to the control group. It can be concluded that for the risk assessment of premature atherosclerotic changes, but also renal failure progression in patients with CRF, determination of the Lp(a) serum concentration is recommendable. Kratak sadr`aj: Kardiovaskularne bolesti su vode}i uzrok mortaliteta kod bolesnika sa hroni~nom bubre`nom insuficijencijom (HBI). Me|u faktorima koji doprinose razvoju kardiovaskularnih bolesti je i povi{ena serumska koncentracija lipoproteina(a) koja se bele`i kod ovih bolesnika, naro~ito u terminalnom stadijumu HBI. Me|utim, povi{ena koncentracija lipoproteina(a) mogla bi imati ulogu i u progresiji bubre`ne insuficijencije. Cilj ove studije je da ispita serumske nivoe lipoproteina(a) u hroni~noj bubre`noj insuficijenciji, kao i da utvrdi odnos izme|u stepena o~uvanosti bubre`ne funkcije i nivoa tog lipoproteina. Ova studija preseka je obuhvatila 127 ispitanika koji su podeljeni u tri grupe. Prvu grupu su ~inila 42 (15 ` i 27 m) ispitanika u razli~itim stadijumima HBI, drugu grupu 32 (7 ` i 25 m) ispitanika na hroni~nom programu hemodijalize, i kontrolnu grupu su ~inila 53 (22 ` i 31 m) ispitanika sa urednom bubre`nom funkcijom. Dobijeni rezultati ukazuju na zna~ajno ve}u u~estalost hiper-Lp(a) lipoproteinemije kod dijaliziranih bolesnika u odnosu na kontrolnu grupu, kao i zna~ajno vi{e vrednosti Lp(a) kod obe grupe bolesnika u odnosu na kontrolnu grupu. Mo`e se zaklju~iti da je u cilju procene rizika za razvoj prevremenih aterosklerotskih promena, ali i progresije bubre`ne insuficijencije, kod bolesnika sa HBI preporu~ljivo odre|ivati serumsku koncentraciju Lp(a). Keywords: chronic renal failure, lipoprotein(a) Klju~ne re~i: hroni~na bubre`na insuficijencija, lipoprotein (a) Address for correspondence: Mr sc med dr Velibor ^abarkapa Center for Laboratory Medicine Clinical Center of Vojvodina Hajduk Veljkova 1 21000 Novi Sad, Serbia e-mail: veliborcabarkapaªgmail.com List of abbreviations: Lp(a) – Lipoprotein(a), GFR – Glomerular Filtration Rate, ClCr – Creatinine Clearance, CRF – Chronic Renal Failure, BMI – Body Mass Index, HD – Hemodialysis. JMB 2009; 28 (2) Introduction Chronic renal failure (CRF) is a common health problem worldwide. The prevalence of chronic renal failure is on the rise, since it is a consequence of the increased development of diseases causing renal function disturbances, principally diabetes mellitus and arterial hypertension (1). In patients with chronic renal failure, and especially with end-stage renal disease, cardiovascular diseases are the leading cause of morbidity and mortality. Based upon data on renal patients from different countries, the cardiovascular mortality in this population is about 16 times higher compared to the healthy population (2). Numerous parameters contribute to accelerated atherogenesis and occurrence of cardiovascular diseases in patients with CRF, and the most important ones are: lipid metabolism disturbances, oxidative stress, inflammation, physical inactivity, hypertension, vascular calcifications, endothelial dysfunction and depressed nitric oxide availability (3–6). Many of the renal disease patients have dyslipidaemia, often already in an early stage of renal failure (7, 8). Apart from quantitative abnormalities (hypertriglyceridaemia and hypo-HDL cholesterolaemia), in CRF there are also qualitative ones, i.e. disturbance in plasmatic lipoprotein structure (small dense LDL and HDL particles) (9). Furthermore, elevated lipoprotein(a) [Lp(a)] serum concentration was also reported. Lp(a) is an LDL-like lipoprotein that consists of an LDL particle to which the glycoprotein apolipoprotein (apo)(a) is bound. Lipoprotein(a) serum levels vary widely, with a distribution that is skewed at low levels. The apo(a) gene is located on chromosome 6 and is the major gene controlling lipoprotein(a) levels. In Lp(a) catabolism, the liver is without any function, and it is supposed that kidney is the dominant organ. The presence of apo(a) fragments liberated from the lipoprotein complex was established in urine in quantity of 1% of the total Lp(a) catabolism, which is in correlation with its plasmatic levels (10). There is a possibility that it is an active tubular secretion mechanism. Numerous studies reported elevated Lp(a) levels in patients with kidney diseases. This increase, however, depends markedly on the impairment of kidney function, the amount of proteinuria, and the treatment modality. In addition to these parameters, there is strong evidence that the relative increase of Lp(a) also depends on the apo(a) K-IV repeat polymorphism (11). Lipoprotein(a), a genetically determined lipoprotein in the blood, is one of the most powerful independent risk factors for cardiovascular disease (12). Lp(a) levels above 0.30 g/L were proposed to be associated with an increased risk. However, the Lp(a) level itself seems to be less discriminative for cardiovascular disease in kidney patients compared with the general population (11). 83 Based upon previous research, it is known that endothelial function disturbance, infiltration of intimal endothelial surface of the arterial wall with native LDL particles, their oxidative modification, monocyte mobilization, migration and proliferation of smooth muscle cells, extracellul (...truncated)