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A role for organic anion transporters OAT1 and OAT3 in renal secretion of creatinine
Author(s) -
Vallon Volker,
Eraly Satish,
RamachandraRao Satish,
Gerasimova Maria,
Nagle Megha,
Sharma Kumar,
Nigam Sanjay,
Rieg Timo
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.838.1
Tubular secretion of creatinine is known to limit its value as a marker of GFR but the molecular determinants of this pathway are unclear. Organic anion transporter OAT1 and OAT3 are expressed on the basolateral membrane of proximal tubules and transport organic anions but also some neutral compounds and cations. We report that plasma creatinine concentrations are greater in male mice lacking Oat1(−/−) than wild‐type (WT) mice (0.134±0.008 vs 0.107±0.008mg/dl; n=12; P=0.019)(0.111±0.007mg/dl in Oat3−/−). Renal clearance of creatinine was greater than of FITC‐inulin in WT (delta clearance (d‐Cl) 47±5%; P<0.004) consistent with renal creatinine secretion. A significant difference was lacking in Oat1−/− (d‐Cl ‐6±12%; NS) and the difference was attenuated in Oat3−/− (d‐Cl 12±9%; P<0.01 vs WT). Studies in Xenopus oocytes microinjected with mOat1 and mOat3 showed that either transporter mediated significant uptake of 14C‐creatinine; at 10μM (0.114mg/dl; physiological levels) creatinine uptake was at least four‐fold greater than in control studies (uninjected or probenecid‐inhibited oocytes). Estimated Km and Vmax values were similar for mOat1 & mOat3 (7.8 & 18.1mM; 373 & 618pmole/oocyte/h). The low affinity of creatinine may be compensated by the relatively high transport capacity of these OATs (high Vmax). The data implicate OAT1 and OAT3 in the renal secretion of creatinine. (Funded by NIH HL094728 )