RESUMO
Enkephalins are involved in the regulation of renal function. Proenkephalin A, also known as PenKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. PenKid is used for prediction and diagnosis of AKI, and need of renal replacement therapy (RRT). PenKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of PenKid is affected or not by RRT, is a controversial point and there are no studies describing the kinetics of the molecule. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study is to determine the sieving coefficient and the diffusive clearance of PenKid in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively and also Penkid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin. In each experiment, the blood batch was adjusted at 1000 mL, maintained at 37° and stirred; blood was spiked with a lyophilized PenKid peptide. Samples were collected from blood, ultrafiltrate, and effluent at different times. Sieving, clearance and removal ratio were calculated. Significant removal of PenKid was observed in CVVH (sieving 1.04±0.27), CVVHD (clearance 23.08±0.89) and HA (removal ratio 76.1±1% after 120 minutes). PenKid is effectively removed by extracorporeal therapies. In presence of anuria, PenKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.
RESUMO
INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) are known water pollutants leading to potential public health consequences. High blood levels of PFAS have been associated with several pathological conditions including testicular and kidney cancer. Classic extracorporeal therapies have demonstrated limited efficiency and new approaches should be explored. In this study we studied the possible role of hemoadsorption to achieve a fast, safe and effective removal of PFAS from blood in patients with high blood levels. METHODS: We developed an in vitro model of hemoadsorption to test the potential of PFAS removal by extracorporeal treatment. We recirculated a highly polluted batch of water (4 liters) through a sorbent cartridge (Jafron medical, Zuhai, China) for 120 minutes at a flow of 150 mL/min. We collected samples at different time points and analyzed 39 different PFAS compounds. RESULTS: For the PFAS compounds with concentrations significantly above normal, we observed a removal ratio close to 90% already within the first 60 minutes of circulation leading to almost complete elimination of all pollutants at 120 minutes. CONCLUSIONS: The in vitro model of hemoadsorption suggests the possible application in vivo of this technique to reduce/normalize the concentrations of PFAS in patients exposed to water or environmental pollution.