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

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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.

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  1. Chang K. Shim

    Present address: College of Pharmacy, Seoul National University, San 56-1, Shinrim-Dong, Kwanak-ku, Seoul, Korea

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  1. Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, 113, Tokyo, Japan

    Yasufumi Sawada, Tatsuji Iga & Manabu Hanano

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Abstracted in part from a dissertation submitted by Chang K. Shim to the Graduate School, Division of Pharmaceutical Sciences, University of Tokyo, in partial fulfilment of the Doctor of Philosophy degree requirements. This study was supported by a grant-in-aid for Scientific Research provided by the Ministry of Education, Science and Culture of Japan.

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Shim, C.K., Sawada, Y., Iga, T. et al. Estimation of renal secretory function for organic cations by endogenous N1-methylnicotinamide in rats with experimental renal failure. Journal of Pharmacokinetics and Biopharmaceutics 12, 23–42 (1984). https://doi.org/10.1007/BF01063609

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