Transfer of uremic solutes across the human term placenta: An ex vivo study in the dual-side perfused cotyledon

Introduction: An increasing number of women becomes pregnant while suffering from chronic kidney disease (CKD). As a result of decreased renal function, uremic solutes circulate at high levels in the maternal circulation. This study aimed to acquire more knowledge about the placental transfer of uremic solutes across the human placenta. Methods: Placental transfer was studied in healthy term placentas, via the ex vivo dual-side human cotyledon perfusion technique (closed-closed set-up for both maternal and fetal circulations). Uremic solute concentrations in maternal and fetal perfusates were measured via LC-MS/MS over 180 min of perfusion. Results: We found that the studied compounds demonstrated different degrees of placental transfer. Fetal-tomaternal perfusate ratios at t = 180 min were for anthranilic acid 1.00 +/- 0.02, indole-3-acetic acid 0.47 +/- 0.08, hippuric acid 0.36 +/- 0.18, 1-arabinitol 0.33 +/- 0.04, indoxyl sulfate 0.33 +/- 0.11, neopterin 0.28 +/- 0.14 and kynurenic acid 0.13 +/- 0.03. All uremic solutes studied also emerged in the perfusates when cotyledons were perfused in the absence of uremic solute concentrations added to the maternal reservoir. For kynurenin these concentrations were so high, it complicated the calculation of a transfer ratio for the exogenously administered compound. Discussion: After 180 min of exposure the extent of placental transfer differs substantially for the solutes studied, reflecting different transfer rates. Future studies should investigate to what extent specific uremic solutes reach the fetal circulation in vivo and how they may interfere with organ function and development of the unborn child.