4.2 Review

Update on the glomerular filtration barrier

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出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MNH.0b013e3283296044

关键词

gel permeation; glomerular filtration barrier; permselectivity; podocytes; proteinuria

资金

  1. National Institutes of Health [R01DK078314, R21DK074613, P30DK079333]
  2. American Heart Association
  3. Alaska Kidney Foundation-American Society of Nephrology Research Grant (George Jarad)
  4. National Institutes of Health and American Heart Association
  5. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK074613, P30DK079333, R01DK078314] Funding Source: NIH RePORTER

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Purpose of review The nephrology community lacks a unified view of protein sieving through the glomerular capillary wall. The glomerular capillary wall consists of three distinct but closely interacting layers: the fenestrated endothelium, with its glycocalyx; the podocytes, with their interdigitated foot processes and slit diaphragms; and the intervening glomerular basement membrane. Proteinuria is associated with abnormalities in any one layer, suggesting that each contributes to the glomerular filtration barrier (GFB). Proteinuria can also be induced in the context of a normal glomerular capillary wall. Here, we review some classic studies as well as some newer concepts and present competing hypotheses about the GFB. Recent findings Two almost forgotten concepts have recently emerged. One group has challenged the exquisite selectivity of the GFB to albumin and suggested that proteinuria is the result of abnormal tubular uptake. There has also been a reemphasis on diffusion through the glomerular basement membrane as the driving force behind macromolecular filtration. New evidence suggests that the endothelial glycocalyx is an important charge-selective barrier. Summary We suggest viewing the GFB as a dynamic rather than as a rigid barrier, requiring three healthy layers and a hemodynamic steady state. Multiple challenges to studying the endothelium, the tubular handling of albumin, and the role of hemodynamic forces will require new tools, new hypotheses, and open minds.

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