Estimation of renal secretory function for organic cations by endogenous N1-methylnicotinamide in rats with experimental renal failure

Abstract

To assess whether the secretory clearance of N ¹-methylnicotinamide (NMN), an endogenous organic cation, represents renal tubular secretion of the organic cation, the relationship between the secretory clearance of NMN, CL _scn(NMN),and that of tetraethylammonium bromide (TEA), CL _scn(TEA),was examined in normal and experimental renal failure (ERF) rats. TEA was selected as a representative organic cation secreted by the kidney. ERF was induced by glycerol, folate, salicylate, uranium, and gentamicin, substances which have been demonstrated to produce specific damage to the kidney by pathophysiological studies. Glomerular filtration rate (GFR), CL _scn(NMN),and CL _scn(TEA) decreased significantly in most of ERF rats, while blood urea nitrogen (BUN) increased significantly in all ERF rats. There was a statistically significant correlation (r=0.952, p<0.001) between the endogenous CL _scn(NMN) and CL _scn(TEA) in both the normal and ERF rats. Correlation analysis revealed that CL _scn(NMN) was superior to GFR in the degree of relationship to CL _scn(TEA),but BUN could not be used as an index for the secretion of NMN or TEA. Although the plasma concentration of NMN in most of the ERF rats was much higher than that in the normal rats, it affected neither the urinary clearance of NMN itself nor the excretion of TEA. From these findings, we propose that CL _scn(NMN) can be used as an index to assess renal tubular function for the secretion of organic cations that are excreted by both filtration and secretion without reabsorption.