Role of the kidney in the metabolism of apolipoprotein A-IV: influence of the type of proteinuria.
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.
Lingenhel
Arno
A
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Lhotta
Karl
K
Neyer
Ulrich
U
Heid
Iris M
IM
Rantner
Barbara
B
Kronenberg
Martina F
MF
König
Paul
P
von Eckardstein
Arnold
A
Schober
Maria
M
Dieplinger
Hans
H
Kronenberg
Florian
F
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
D001054:Apolipoproteins A; D012709:Serum Albumin; C022205:apolipoprotein A-IV; D003404:Creatinine