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Nephrol Dial Transplant (1997) 12: 2673–2678
Nephrology Dialysis Transplantation
Original Article
Urinary excretion of apo(a) in patients after kidney transplantation K. M. Kostner1, R. Oberbauer2, U. Hoffmann1, T. Stefenelli1, G. Maurer1 and B. Watschinger2 1Second Department of Medicine, Division of Cardiology, 2Third Department of Medicine, Division of Nephrology, University of Vienna
Abstract Background. Increased plasma Lipoprotein (a) (Lp(a)) levels are strongly associated with premature cardiovascular disease and stroke. The kidney is purported to play an important role in apo(a) catabolism. Therefore we investigated plasma Lp(a) levels in relation to kidney function and urinary apo(a) excretion. Methods. One hundred and sixteen kidney transplant patients with normal or impaired renal function and 109 age- and sex-matched healthy controls were investigated. Plasma Lp(a) and urinary apo(a) levels were determined immunochemically and all other parameters were determined by routine laboratory methods. Results. Transplant recipients were found to have significantly elevated total cholesterol and LDL-C values, but equal HDL-C values compared to controls. Plasma Lp(a) values were higher and urinary apo(a) excretion was lower in transplant recipients compared to controls, independent of renal function. When the patient group was subdivided into ‘normal’ and ‘impaired creatinine clearance’, only the latter group secreted less apo(a) than normal controls. Conclusion. These data suggest that urinary apo(a) excretion is reduced in transplant recipients with impaired excretory graft function, which may contribute to the elevation of plasma Lp(a) levels in these patients. Key words: function
Lp(a) metabolism; proteinuria; renal
Introduction Because of the strong correlation between high plasma Lp(a) levels and coronary artery disease, stroke and peripheral atherosclerosis [1–5], Lp(a) has been established as an independent risk factor for atherosclerotic disease. In addition, Lp(a) has appeared as a predictor of myocardial infarction in several prospective and Correspondence and offprint requests to: Dr Karam Kostner, AKH Wien, Dept. of Cardiology, Waehringerguertel 18–20, A–1090 Vienna, Austria.
case controlled studies [2–6 ]. Protein and cDNA sequencing of apo(a) revealed a high degree of homology to plasminogen [7] and by inhibiting plasminogen activation in a template-dependent manner, Lp(a) was found to inhibit fibrinolysis [8]. Lp(a) also has a high affinity for proteoglycans, which is probably the reason why it is found in high amounts in atherosclerotic plaques [9]. Therefore Lp(a) has become one of the most widely studied lipoproteins in atherosclerosis research. Despite this flurry of activity in Lp(a) research, little is known about its physiological function and catabolism. Lp(a) has been shown to bind to the LDL-receptor in vitro, yet in vivo LDL-receptormediated catabolism seems to play only a minor role in the removal of Lp(a) [10]. There are several indications that the kidney plays an important role in Lp(a) metabolism. Following the first report by Parra et al. in 1987 [11], various publications have appeared with the unanimous finding that patients with uraemia and nephrotic syndrome have a three- to fivefold increase in their plasma Lp(a). Patients with nephrotic syndrome, for example, exhibit excessively high plasma Lp(a) concentrations, which can be reduced by antiproteinuric therapies [12–14]. Patients with end-stage renal disease ( ESRD) treated with haemodialysis are also found to have elevated Lp(a) levels and these are even higher in patients treated with continuous ambulatory peritoneal dialysis [16 ]. There are several reports in the literature on Lp(a) levels in patients undergoing renal transplantation (for an extensive review see [15]. In some reports, Lp(a) levels decrease to control levels after transplantation [17–19,23]. The main reason for diverging results in the literature might be the study design (small casecontrol versus prospective studies). It was recently reported that apo(a) immunoreactivity is found in urine [20–22]. However, it is not intact Lp(a) that is secreted, but rather apo(a) fragments. Independent of the apo(a) isoform, we consistently found more than 10 distinct apo(a) bands in urine with molecular masses between 50 and 160 kDa and with a rather characteristic pattern. These apo(a) fragments were found to be glycosylated and not complexed to apoB. We previously reported a highly significant correlation between urinary apo(a) concen-
© 1997 European Renal Association–European Dialysis and Transplant Association
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trations, and plasma Lp(a) levels (R=0.68, P
