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.