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Published ahead of print on December 28, 2005
J Am Soc Nephrol 17: 528-536, 2006
© 2006 American Society of Nephrology
doi: 10.1681/ASN.2005070733
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Epidemiology and Outcomes

Apolipoprotein A-IV Predicts Progression of Chronic Kidney Disease: The Mild to Moderate Kidney Disease Study

Eva Boes*, Danilo Fliser{dagger}, Eberhard Ritz{ddagger}, Paul König§, Karl Lhotta§, Johannes F.E. Mann||, Gerhard A. Müller, Ulrich Neyer#, Werner Riegel**, Peter Riegler{dagger}{dagger}, Florian Kronenberg* for the MMKD Study Group

* Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Austria; {dagger} Department of Internal Medicine, Hannover Medical School, Hannover, Germany; {ddagger} Department of Internal Medicine, Division of Nephrology, Ruperto-Carola-University, Heidelberg, Germany; § Innsbruck University Hospital, Department of Clinical Nephrology, Innsbruck, Austria; || München General Hospitals, Department of Nephrology, LMU, Munich, Germany; Department of Nephrology and Rheumatology, Georg-August-University, Göttingen, Germany; # Feldkirch Hospital, Department of Nephrology, Feldkirch, Austria; ** Medizinische Universitätskliniken des Saarlandes, Innere Medizin IV, Homburg/Saar, Germany; and {dagger}{dagger} Bozen Hospital, Division of Nephrology and Hemodialysis, Bozen, Italy

Address correspondence to: Dr. Florian Kronenberg, Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstrasse 41, A-6020 Innsbruck, Austria. Phone: +43-512-507-3490; Fax: +43-512-507-2680 or 9804; E-mail: florian.kronenberg{at}i-med.ac.at

Received for publication July 15, 2005. Accepted for publication November 22, 2005.

It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n = 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m2; P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P = 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype {epsilon}2/{epsilon}4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.




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