title: Role of the kidney in the metabolism of apolipoprotein A-IV: influence of the type of proteinuria.
abstract: Increased plasma concentrations of apolipoprotein A-IV (apoA-IV) in chronic renal disease suggest a metabolic role of the kidney for this antiatherogenic protein. Therefore, we investigated patients with various forms of proteinuria and found increased serum concentrations of apoA-IV in 124 nephrotic patients compared with 274 controls (mean 21.9 +/- 9.6 vs. 14.4 +/- 4.0 mg/dl; P < 0.001). Decreasing creatinine clearance showed a strong association with increasing apoA-IV levels. However, serum albumin levels significantly modulated apoA-IV levels in patients with low creatinine clearance, resulting in lower levels of apoA-IV in patients with low compared with high albumin levels (21.4 +/- 8.6 vs. 29.2 +/- 8.4 mg/dl; P = 0.0007). Furthermore, we investigated urinary apoA-IV levels in an additional 66 patients with a wide variety of proteinuria and 30 controls. Especially patients with a tubular type of proteinuria had significantly higher amounts of apoA-IV in urine than those with a pure glomerular type of proteinuria and controls (median 45, 14, and 0.6 ng/mg creatinine, respectively). We confirmed these results in affected members of a family with Dent's disease, who are characterized by an inherited protein reabsorption defect of the proximal tubular system. In summary, our data demonstrate that the increase of apoA-IV caused by renal impairment is significantly modulated by low levels of serum albumin as a measure for the severity of the nephrotic syndrome. From this investigation of apoA-IV in urine as well as earlier immunohistochemical studies, we conclude that apoA-IV is filtered through the normal glomerulus and is subsequently reabsorbed mainly by proximal tubular cells.
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Arno
authors.initials: A
authors.lastname: Lingenhel
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
authors.forename: Ulrich
authors.initials: U
authors.lastname: Neyer
authors.forename: Iris M
authors.initials: IM
authors.lastname: Heid
authors.forename: Barbara
authors.initials: B
authors.lastname: Rantner
authors.forename: Martina F
authors.initials: MF
authors.lastname: Kronenberg
authors.forename: Paul
authors.initials: P
authors.lastname: König
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: Maria
authors.initials: M
authors.lastname: Schober
authors.forename: Hans
authors.initials: H
authors.lastname: Dieplinger
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D000328:Adult; D000368:Aged; D001054:Apolipoproteins A / Q000097:blood*; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000378:metabolism / Q000503:physiopathology; D011507:Proteinuria / Q000097:blood*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D012709:Serum Albumin; C022205:apolipoprotein A-IV; D003404:Creatinine