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Lipoprotein(a) Levels in the Nephrotic Syndrome
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TO THE EDITOR:
We read with interest the article by Wanner and colleagues [1] reporting that plasma lipoprotein(a) (Lp[a]) levels are elevated in patients with the nephrotic syndrome. The authors speculated that decreased oncotic pressure might stimulate hepatic protein secretion, and as apolipoprotein(a) (apo[a]) is synthesized by the liver, this might result in elevated plasma levels. Also, if the kidney has a role in Lp(a) catabolism, deterioration of function might lead to increased plasma Lp(a) levels. We suggest further possibilities related to the physical characteristics of Lp(a) itself.
Lipoprotein(a) is a large particle, similar in composition to low-density lipoprotein, except that the unique protein component, apo(a), is attached by covalent linkage to apolipoprotein B (apo B). Apolipoprotein(a) isoforms range in molecular weight from 238 to 643 kDa [2]; the molecular weight of apo B is 512 to 550 kDa. Further, apo(a) is heavily sialated [3], a factor that leads to significant negative charge.
The nephrotic syndrome is associated with heavy proteinuria, which can result from defects in glomerular charge-selective or size-selective barriers or both [4]. In general, an inverse relation exists between protein molecular size and clearance rate, which might lead to selective increases (or decreases) in serum levels of a particular protein. For example, whereas serum levels of albumin (66.5 kDa) are invariably decreased in patients with the nephrotic syndrome, levels of α2 macroglobulin (725 kDa), pentameric IgM (971 kDa), and ferritin (450 kDa) are increased [4, 5]. The Lp(a) molecule is also large, and plasma Lp(a) levels might therefore be increased because of a size selectivity effect.
Wendy Y. Craig, PhD
Robert F. Richie, MD
Foundation for Blood Research; Scarborough, ME
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
