Thomas ME, Brunskill NJ, Harper SJ, Harris KPG, Furness PN, Walls J
Fatty acids on albumin cause injurious effects in protein overload proteinuria
Am Soc Nephrol
J Am Soc Nephrol (abstract) (Sep) 7:1866 1996

In many forms of chronic renal disease the magnitude of proteinuria correlates strongly with the degree of subsequent renal injury and ultimate clinical course. The concept of toxic fatty acids attached to albumin causing macrophage chemotaxis was proposed several years back by George F. Schreiner.

In this study, which is one of the rare non-human studies we review on HDCN, either fatty acid-bearing bovine serum albumin (FA-BSA) or delipidated (DL-)BSA was injected IP into rats for 7 days. On day 7, kidneys were perfused in situ and the degree of cortical macrophage infiltration was assessed by immunoperoxidase staining.

FA-BSA provoked a substantially higher degree of cortical and macrophage influx and tubulo-interstitial proliferation.

Comment: Schreiner's original observations, published several years ago, have not received much follow-up. In particular, he showed that ethanol administration markedly attenuated macrophage infiltration provoked by FA attached to albumin, presumably via inhibition of some metabolic pathway. Clinically, the results suggest that one might be cautious in administering albumin to severely nephrotic patients. Also, much more work needs to be done to determine the mechanism of chemotaxis and injury of these fatty acids, and to identify the FA which are responsible. Presumably, one might be able to block this pathway and to help preserve renal function in severely proteinuric patients. (John T. Daugirdas, M.D., University of Illinois at Chicago)

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Am Soc Nephrol
Proteinuria/Hematuria : Mechanisms of renal injury
CRF by problem area : Progression

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