Optimized Renal Transporter Quantification by Using Aquaporin 1 and Aquaporin 2 as Anatomical Markers: Application in Characterizing the Ontogeny of Renal Transporters and Its Correlation with Hepatic Transporters in Paired Human Samples

AAPS J. 2019 Jul 11;21(5):88. doi: 10.1208/s12248-019-0359-1.


Renal transporters, which are primarily located in the proximal tubules, play an important role in secretion and nephrotoxicity of drugs. The goal of this study was to characterize the age-dependent protein abundance of human renal transporters. A total of 43 human kidneys, 26 of which were paired with livers from the same donors, were obtained and classified into three age groups: children (< 12 years), adolescents (12 to < 18 years), and adults (> 18 years). Protein abundance of kidney-specific anatomical markers, aquaporins 1 and 2 (markers of proximal and distal/collecting tubules, respectively), and 17 transporters was quantified by LC-MS/MS proteomics. Six out of 43 kidney samples were identified as outliers (Grubbs' test) that were significantly different from the others with relatively higher aquaporin 2 to aquaporin 1 ratio, indicating that these cortex samples were likely contaminated by medulla (representing distal/collecting tubules). No significant age-related changes (age > 1 year) were observed for renal transporter abundance, albeit OCT2 abundance was modestly higher (< 50%) in adolescents than that in adults. Higher protein-protein correlation between transporters was observed in the kidney but abundance of transporters between tissues was not correlated. The use of aquaporins 1 and 2 provides a method for identifying kidney cortex with significant contamination from medulla containing distal and collecting tubules. The abundance and protein-protein correlation data can be used in physiologically based pharmacokinetic (PBPK) modeling and simulation of renal drug disposition and clearance in pediatric populations.

Keywords: kidney; liver; ontogeny; paired samples; quantitative proteomics; renal transporters.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aquaporin 1 / metabolism*
  • Aquaporin 2 / metabolism*
  • Child
  • Child, Preschool
  • Chromatography, Liquid
  • Female
  • Humans
  • Infant
  • Kidney / metabolism*
  • Kidney Tubules, Collecting / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Liver / metabolism
  • Male
  • Membrane Transport Proteins / metabolism*
  • Tandem Mass Spectrometry
  • Young Adult


  • Aquaporin 2
  • Membrane Transport Proteins
  • Aquaporin 1