Mechanisms for the Progression of Renal Disease - Fatty Acids as an Aggravating Factor and Fatty Acid Binding Protein as an Ameliorating Factor

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In order to clarify the pathogenesis of the tubulointerstitial damage by proteinuria, we performed the following experiments.Bovine serum albumin (BSA) was intraperitoneally injected for 2 weeks. Normal BSA induced remarkable tubulointerstitial damage, while defatted BSA did mild tubulointerstitial damage. The cultured proximal tubules similarly took normal BSA and defatted BSA into the cytoplasm. We established transgenic mice where human L-FABP was expressed in the proximal tubule. Intraperitoneal injection of normal BSA into the transgenic mice made severe tubulointerstitial damage and the expression of L-FABP was enhanced. Urinary excretion of L-FABP was increased. However, defatted BSA induced only mild tubulointerstitial damage. Neither the renal expression of L-FABP nor the urinary excretion of L-FABP was changed.In conclusion, fatty acid bound to albumin play an important role in the pathogenesis of the tubulointerstitial damage induced by proteinuria. Fatty acid stress to the proximal tubule increased the renal expression and urinary excretion of L-FABP.