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Apolipoprotein A-IV serum concentrations are elevated in patients with mild and moderate renal failure
Florian Kronenberg1, Erich Kuen1, Eberhard Ritz1
1*Institute of Medical Biology and Human Genetics, University of Innsbruck, Innsbruck, Austria; Department of Internal Medicine, Division of Nephrology, Ruperto-Carola-University, Heidelberg, Germany; Innsbruck University Hospital, Department of Clinical Nephrology, Austria; Department of Internal Medicine A, Ernst-Moritz-Arndt-University Greifswald, Germany; München Schwabing Hospital, LMU, Munich, Germany; Department of Nephrology and Rheumatology, Georg-August-University, Göttingen, Germany; Feldkirch Hospital, Department of Nephrology and Dialysis Feldkirch, Austria; **Medizinische Universitätskliniken des Saarlandes, Innere Medizin IV, Homburg/Saar, Germany; Bozen Hospital, Division of Nephrology and Hemodialysis, Bozen, Italy; and Institute of Clinical Chemistry and Laboratory Medicine and Institute of Arteriosclerosis Research, University of Münster, Germany.
Abstract:
Cell culture studies and investigations in mice that overexpress either human or mouse apolipoprotein A-IV (apoA-IV) revealed anti-atherogenic properties of apoA-IV. An association between low apoA-IV concentrations and coronary artery disease in humans was demonstrated; therefore, apoA-IV may also play an antiatherogenic role in humans. Because apoA-IV is markedly elevated in dialysis patients, patients with the earliest and modest stages of renal impairment were studied to assess the association of apoA-IV with GFR and atherosclerotic complications. GFR was measured by the use of iohexol in 227 non-nephrotic patients with different degrees of renal impairment. ApoA-IV increased significantly with decreasing GFR and was already elevated in earliest stages of renal disease (GFR > 90 ml/min per 1.73 m2). Multiple linear regression analysis identified renal function parameters (GFR, creatinine, and urea) as the most important determinants of apoA-IV levels in serum of these patients. Twenty-six patients had already experienced 36 atherosclerotic events. Logistic regression analysis identified three variables associated with atherosclerotic complications: age, apoA-IV, and gender. Each 1 mg/dl increase of apoA-IV decreased the odds ratio for an atherosclerotic complication by 8% (P = 0.011). The data clearly show that the anti-atherogenic apoA-IV starts to increase during the earliest phases of renal insufficiency, which makes apoA-IV an early marker of renal impairment.