Contribution of proteinuria to progressive renal injury: consequences of tubular uptake of fatty acid bearing albumin.
Proteinuria is a marker of a poor prognosis in the glomerulonephritides and progressive renal disease. Recent animal studies have directly implicated proteinuria in inflammatory tubulointerstitial injury. The proximal tubule takes up significant amounts of lipid in the human nephrotic syndrome. We propose that proximal tubular uptake and metabolism of lipids, notably fatty acid bearing albumin, contributes to the chronic tubulointerstitial infiltration and injury associated with heavy proteinuria. Work in our laboratory has shown that a novel nonpolar lipid released by proximal tubules endocytosing fatty acid-bearing albumin is a potent macrophage chemoattractant. We have also studied the metabolic destiny of fatty acids liberated upon proximal tubular catabolism of albumin. Palmitate was preferentially metabolized to phosphatidylcholines, phosphatidylinositols and diglycerides. Oleate and linoleate were metabolized to triglycerides. Palmitate was profoundly inhibitory to OK cell growth, whilst oleate was stimulatory. In nephrosis, faced with an unregulated influx of fatty acids on albumin, the proximal tubule metabolizes them to a variety of lipids, some of which have pathological effects. Thus, the metabolism of albumin-bound fatty acids by the proximal tubule during heavy proteinuria may directly underlie subsequent tubulointerstitial inflammation and altered response to injury.
Thomas
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ME
Renal Division, Washington University School of Medicine, St Louis, MO 63110.
Schreiner
G F
GF
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D005921:Glomerulonephritis / Q000150:complications* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D011507:Proteinuria / Q000150:complications*
D000418:Albumins; D005227:Fatty Acids