Research database

Continuous renal replacement therapy (CRRT) is frequently applied in critically ill patients with acute kidney injury to counteract fluid overload and to remove wasted solutes retained due to kidney dysfunction. Indeed, during CRRT plasma water and solutes are removed from the patient’s blood, being forced through the semipermeable membrane of the hemodiafilter. The ultrafiltration coefficient (Kuf) and the sieving coefficient (SC) are those performance characteristics that quantify the membrane capability of being crossed by plasma water and solutes. Unfortunately, Kuf and SC decrease unpredictably (and often undetectably) during the treatment due to membrane fouling (i.e., an unquantifiable phenomenon that always occurs during CRRT), leading to undertreatment and affecting the patient’s outcomes. New bedside, realtime, inexpensive, and feasible methods to quantify Kuf and SC and their overtime reduction are needed to tailor CRRT to the patient's actual needs, with the ultimate goal of efficiently removing plasma water (to counteract fluid overload) and purifying wasted solutes. Furthermore, since a significant number of CRRT is performed in septic patients, the transmembrane antibiotic removal should be precisely controlled. The amount of antibiotic loss in the effluent is virtually unknown in most CRRT prescribed in critically ill septic patient. The inability to quantify antibiotic clearance and restore transmembrane leakage by increasing antibiotic dosage severely worsens patient outcomes. A bedside method to realistically estimate the transmembrane loss of antibiotics during CRRT may support physicians to precisely and dynamically readjust antibiotic posology with the ultimate goal to reach clinically relevant pharmacokinetic/pharmacodynamics targets. This project aims at improving precision medicine in the field of CRRT performed on critically ill patients in the ICU. The effects of membrane fouling will be explored in terms of Kuf (workpackage 1, WP1) and SC (WP2) reduction overtime. Behind the identification and prevention of membrane fouling, the concept of a more precise ability to maintain control over transmembrane clearance will be explored for CRRT antibiotic removal (WP3). Through multidisciplinary cooperation among four academic centers allowing the engineering, biological and pharmacological analysis of clinical and technological data obtained from bedside practice, this project will: 1)Define and clinically validate a new method for instantaneous Kuf estimation during CRRT (WP1); 2) Define and clinically validate a data-driven based method to predict Kuf reduction overtime due to membrane fouling (WP1); 3)Design a decision support system that can help physicians to readjust the CRRT prescription to prevent Kuf reduction overtime (WP1); 4)Define and clinically validate an innovative method for SC profiling during CRRT (WP2); 5) Define and clinically validate a new method to estimate transmembrane antibiotic removal (WP3).