Cross-species overview of renal drug transporters
Fetal-adult relations have not been described in nonhuman primates, dogs, and pigs.
| Transporter | Human | Mice | Rat | Reference(s) |
|---|---|---|---|---|
| PGP | Expression of PGP was noted from GW 5.5. Significant expression by GW 11 with increasing expression after birth and in adults. Protein abundance is lowest in newborns (PND 0–28)/infants (1–24 mo) and reached adult (>16 yr) levels during the child stage (2–12 yr) | Pgp was marginally expressed in newborns and was increased in the postnatal period, with a maximum expression on PND 21. At day 45, there was a decline in males but not females. | Expression was marginal at birth and increased during postnatal stage with highest levels between PND 11–26. | van Kalken et al., 1992; Miki et al., 2005; Pinto et al., 2005; de Zwart et al., 2008; Cui et al., 2009; Konieczna et al., 2011; Sweeney et al., 2011; Xu et al., 2017; Cheung et al., 2019 |
| BCRP | Significant expression was noted at GW 5.5 and 28. BCRP is upregulated in the term newborn and mostly reached adult levels before 2 yr of age. Protein abundance is, however, similar between newborns and adults. | No fetal-adult relation described. | Expression was increased during postnatal stage compared with prenatal stage. During the postnatal stage, expression was remained stable and highest expression was present in the adult stage. | de Zwart et al., 2008; Konieczna et al., 2011; Sweeney et al., 2011; Xu et al., 2017; Cheung et al., 2019 |
| MRP1 | Significant expression was noted at GW 5.5 and 28. | MRP1 was expressed at adult levels at birth. Female expression was predominant. | MRP1 was most highly expressed at birth. | Maher et al., 2005; de Zwart et al., 2008; Konieczna et al., 2011 |
| MRP2 | MRP2 shows similar gene expression levels from prematures (PND 0–28, GW <37) up until adult stages. | MRP2 levels was increased over time to reach adult levels during the 1st weeks of life. | Expression was increased in the postnatal stage compared with prenatal stage. During the postnatal stage, expression was remained stable, but protein was increased and highest expression was presented in the mature stage. | Maher et al., 2005; de Zwart et al., 2008; Sweeney et al., 2011; Nomura et al., 2012; Cheung et al., 2019 |
| MRP3 | No fetal-adult relation described. | MRP3 levels were generally increased over time to reach adult levels. Female expression was predominant. | MRP3 was most highly expressed at birth. | Maher et al., 2005; de Zwart et al., 2008 |
| MRP4 | MRP4 shows similar gene expression levels from prematures up until adult stages. | MRP4 levels were generally increased over time to reach adult levels. Female expression was predominant. | Stable expression during fetal and early postnatal development. Higher expression in adult state. | Maher et al., 2005; Sweeney et al., 2011; Nomura et al., 2012; Xu et al., 2017; Cheung et al., 2019 |
| OATP1A2 (rodent analogs OATP 1, 3–6) | No fetal-adult relation described. | OATP1A1 was hardly present at birth and showed high expression on PND 45 in males but not females. OATP1A4 showed stable expression from PND 2 to 45. OATP1A6 expression started to increase 2 wk after birth. | OATP1A4 peak levels were reached in the 1st week of birth and were then slowly decreased toward adult levels. | Cheng et al., 2005; de Zwart et al., 2008 |
| OCT1 | No fetal-adult relation described. | OCT1 expression was low before birth and was gradually increased in the first two PNW and peaked at PND 22, after which it remained rather stable. | OCT1 expression was increased from late prenatal development up until adult stage. Overall expression was only limited at birth. | Slitt et al., 2002; Alnouti et al., 2006; de Zwart et al., 2008; Sweeney et al., 2011; Ahmadimoghaddam et al., 2013; Xu et al., 2017 |
| OCT2 | Gene expression is lowest in the preterm newborn and reaches adult levels before 2 yr of age. Protein abundance starts to reach adult levels in the child stage. | OCT2 was undetected before birth, had a stable expression after birth, and was increased somewhat at PND 22. From PND 30 onward, expression increased sharply in males but remained unchanged in females. | OCT2 was slightly increased from the prenatal phase on but showed significantly increased expression at maturity. | Slitt et al., 2002; Alnouti et al., 2006; Sweeney et al., 2011; Xu et al., 2017; Cheung et al., 2019 |
| OAT1 | OAT1 expression is lowest in preterm newborns and reaches adult levels at term birth or in infants. Protein abundance is lowest in term newborns and infants; levels in children and adolescents (12–16 yr) were approaching adult levels. | Expression was noted on day 15 of gestation and was increased progressively toward adulthood. Organ culture showed positive transport activity. | OAT1 expression was increased during prenatal development, remained stable at postnatal development, and was increased again at the mature age. | Lopez-Nieto et al., 1997; Nakajima et al., 2000; Pavlova et al., 2000; de Zwart et al., 2008; Truong et al., 2008; Hwang et al., 2010; Nagle et al., 2011; Sweeney et al., 2011; Nomura et al., 2012; Xu et al., 2017; Cheung et al., 2019 |
| OAT3 | OAT3 expression is lowest in the preterm newborn and reaches adult levels before 2 yr of age. Protein abundance was lowest in term and newborn infants and rose to adult levels in the adolescent stage. | OAT3 was detected on day 14 of gestation, and expression was gradually increased up to adulthood. | OAT3 expression was increased during the late prenatal development and kept increasing until a mature age. | Pavlova et al., 2000; Buist and Klaassen, 2004; Hwang et al., 2010; Sweeney et al., 2011; Nomura et al., 2012; Xu et al., 2017 |
| OCTn1 | No fetal-adult relation described. | Expression was almost absent on PND -2, was gradually increased PNW 1, and doubled at PNW 2. From PNW 3, it increased again, reaching maximum values around PND 40 | OCTn1 showed 100-fold lower expression compared with adult levels at gestational day 13, and levels started to increase at gestational day 18. Most pronounced upregulation was present in PNW 1 and PNW 4. | Slitt et al., 2002; Alnouti et al., 2006; Sweet et al., 2006; Sweeney et al., 2011 |
| OCTn2 | No fetal-adult relation described. | Very low expression at PND -2, which was increased pronouncedly at PNW 2, and reaches maximum expression around PND 35. | OCTn2 showed 10-fold lower expression compared with adult levels at gestational day 13–18. Most pronounced upregulation present in PNW 1, which was somewhat increased at PNW 4. | Slitt et al., 2002; Alnouti et al., 2006; Sweet et al., 2006; Sweeney et al., 2011 |
| URAT1 | URAT1 expression in infants and children is higher than in term newborns, adolescents, and adults. URAT1 protein abundance was lower in term newborn and infants and reached adult levels at child stage. | URAT1 showed low expression at PND 2, which was greatly increased from PNW 2 onward. | URAT1 main increase in expression was at PNW 1 and 4. | Cheng and Klaassen, 2009; Sweeney et al., 2011 |
| PEPT2 | No fetal-adult relation described. | Pept2 was expressed at PND 2 and was greatly increased at PNW 2. | Pept2 was increased at gestational day 18 and at PNW 4. | Sweeney et al., 2011 |
| MATE1 | MATE1 shows similar expression and protein abundance from premature up to adults. | MATE1 was present during PND 2 but was greatly increased from birth up to PNW 4. | MATE1 was increase steadily throughout gestational day 17–22 and increased more at PNW 4. MATE1 was even increased more at a later age of 6 mo. | Lickteig et al., 2008; Sweeney et al., 2011; Xu et al., 2017; Cheung et al., 2019 |
| NPT | No fetal-adult relation described. | NPT1, 2a, and 2c were expressed at PND 2. Upregulation of the mRNA appears to start at postnatal PNW 2. | No fetal-adult relation described. | Cheng and Klaassen, 2009 |
| ENT | No fetal-adult relation described. | ENT2 was expressed in a low amount at PND -2 and was decreased slightly in the first two PNW and is further reduced at PNW 7. | No fetal-adult relation described. | Cheng and Klaassen, 2009 |