Volume 77, Issue 6, Pages 519-526 (March 2010) Major contribution of tubular secretion to creatinine clearance in mice  Christoph Eisner, Robert Faulhaber-Walter, Yaohui Wang, Asada Leelahavanichkul, Peter S.T. Yuen, Diane Mizel, Robert A. Star, Josephine P. Briggs, Mark Levine, Jurgen Schnermann  Kidney International  Volume 77, Issue 6, Pages 519-526 (March 2010) DOI: 10.1038/ki.2009.501 Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 1 Inulin and creatinine clearances in male and female C57BL/6J mice: effect of cimetidine. Left: Comparison between the clearances of inulin and creatinine in male (a; n=8) and female (b; n=8) C57BL/6J mice without (closed symbols) and with cimetidine-treatment (open symbols). Lines connect simultaneous clearance measurements from individual animals; horizontal bars indicate mean values. Right: Secretion fractions calculated from the difference between creatinine and inulin clearances as indicated in Materials and Methods section. Kidney International 2010 77, 519-526DOI: (10.1038/ki.2009.501) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 2 Measurements of the clearances of inulin (Cin) and creatinine (Ccr) in FVB wild-type mice without (closed symbols) and during PAH administration (open symbols). (a) Male mice under control conditions (n=9) and during PAH administration (n=5) and calculated SFcr (bars on the right). (b) Female mice without treatment (n=12) and with PAH treatment (n=5) and calculated SFcr (bars on the right). Lines connect simultaneous clearance measurements from individual animals and horizontal bars are mean values. Kidney International 2010 77, 519-526DOI: (10.1038/ki.2009.501) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 3 Comparison between the clearances of inulin and creatinine in FVB wild-type and Oct1/2 -/- mice. (a) Inulin and creatinine clearances in male WT (closed symbols; n=9) and OCT1/2 -/- mice (open symbols; n=8) and calculated secretion fractions (bars on the right). (b) Inulin and creatinine clearances in female WT (closed symbols; n=12) and OCT1/2 -/- mice (open symbols; n=7) and calculated secretion fractions (bars on the right). Lines connect simultaneous clearance measurements from individual animals and horizontal bars are mean values. Kidney International 2010 77, 519-526DOI: (10.1038/ki.2009.501) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 4 Effects of PAH, cimetidine, and genetic deletion of OCT1 and OCT2 on plasma creatinine concentration of FVB mice. (a) Plasma creatinine concentrations in FVB wild-type mice without (closed symbols; n=21) and with PAH treatment (open symbols; n=10); horizontal bars indicate mean values. (b) Plasma creatinine concentrations in C57BL/J wild-type mice (closed symbols; n=16) before (control) and during treatment with cimetidine; horizontal bars indicate mean values. (c) Plasma creatinine concentrations in FVB wild-type mice (closed symbols; n=21) and in OCT1/2 -/- (open symbols; n=15); horizontal bars indicate mean values. Kidney International 2010 77, 519-526DOI: (10.1038/ki.2009.501) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 5 Relationship between plasma creatinine concentration and the filtered, excreted, and secreted amounts of creatinine in CD1 mice; plasma creatinine concentration was changed by infusion of creatinine at 5 μg/min (n=5) and 50 μg/min (n=5). Lines represent linear regressions. Kidney International 2010 77, 519-526DOI: (10.1038/ki.2009.501) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 6 Expression of organic anion (OAT) and organic cation (OCT) transporter mRNA in male and female FVB mice. (a) OAT1, OAT2, and OAT3 mRNA quantification in male (closed bars; n=9) and female FVB mice (open bars; n=12); mRNA of OAT1 from male mice was used as reference point (100%). (b) OCT1, OCT2, and OCT3 mRNA quantification in male (closed bars; n=9) and female FVB mice (open bars; n=12); mRNA of OCT1 was set to 100%. (c) OCT3 mRNA quantification in FVB wild-type mice (female: black open bars, n=12; male: black closed bar, n=9) and OCT1/2 -/- mice (female: gray open bar, n=7; male: gray closed bar, n=8); mRNA of FVB wild-type mice was set to 100%. Kidney International 2010 77, 519-526DOI: (10.1038/ki.2009.501) Copyright © 2010 International Society of Nephrology Terms and Conditions