This study is a multicentric randomized controlled trial comparing two groups of patients undergoing single or dual kidney transplantation from deceased donors. To reduce perioperative complications optimal fluid management is essential in patients undergoing kidney transplantation. Heart rate, Medium Arterial Pressure (MAP), Central Venous Pressure (CVP), and urine output have been proposed in the literature to guide perioperative fluid therapy. These criteria are routinely applied in clinical practice; however these criteria have shown low sensitivity and poor predictive of postoperative complication, especially if used alone. The traditional approach in renal transplantation is the volume infusion guided whit CVP to the point of no further fluid responsiveness, but this can lead to excess fluid which can damage the endothelial glycocalyx and lead to organ failure for a fluid shift into the interstitial space.

As a way to reduce postoperative complications in surgical patients, in recent years, several studies have examined Perioperative Goal Directed Therapy (PGDT) as fluid administration guided by optimization of preload with the use of algorithms based on fluids, inotropes and/or vasopressors to achieve a certain goal in stroke volume (SV), cardiac index (CI), or oxygen delivery (DO2). However results regarding the potential role of PGDT cannot be considered definitive, because the various studies on the subject have not all conformed to the same methods and have not uniformly applied the same measurements, so their results regarding the potential role of PGDT cannot be considered definitive.

The aim of this work is to compare the effects of PGDT with conventional fluid therapy in patients undergoing kidney transplantation achievable through implementation of the non invasive monitoring.

To reduce perioperative complications optimal fluid management is essential in patients undergoing kidney transplantation. Heart rate, Medium Arterial Pressure (MAP), Central Venous Pressure (CVP), and urine output have been proposed in the literature to guide perioperative fluid therapy. These criteria are routinely applied in clinical practice; however these criteria have shown low sensitivity and poor predictive of postoperative complication, especially if used alone. The traditional approach in renal transplantation is the volume infusion guided whit CVP to the point of no further fluid responsiveness, but this can lead to excess fluid which can damage the endothelial glycocalyx and lead to organ failure for a fluid shift into the interstitial space.

As a way to reduce postoperative complications in surgical patients, in recent years, several studies have examined Perioperative Goal Directed Therapy (PGDT) as fluid administration guided by optimization of preload with the use of algorithms based on fluids, inotropes and/or vasopressors to achieve a certain goal in stroke volume (SV), cardiac index (CI), or oxygen delivery (DO2). However results regarding the potential role of PGDT cannot be considered definitive, because the various studies on the subject have not all conformed to the same methods and have not uniformly applied the same measurements, so their results regarding the potential role of PGDT cannot be considered definitive.

The aim of this work is to compare the effects of PGDT with conventional fluid therapy in patients undergoing kidney transplantation achievable through implementation of the non invasive monitoring.

MATERIAL AND METHODS. This study is a multicentric randomized controlled trial comparing two groups of patients undergoing single or dual kidney transplantation from deceased donors. All patients who will meet eligibility criteria will be randomised, using a computer generated randomization list, to either Group 1 (PGDT, intervention group) where minimally invasive continuous CI monitor (Edwards ClearSight) will be used to guide a goal directed fluid administration protocol, and Group 2 (control) managed according to local and international best practice guidelines using standard hemodynamic monitoring.

STUDY DESIGN. The study protocol will be developed across the intraoperative and postoperative periods. In the intraoperative phase all standard monitored parameters such as EKG, SpO2 (oxygen saturation by pulse oximetry), airway pressure etc. will be the same for both groups. Where ClearSight minimally invasive monitoring will be used (Group 1), hemodynamic optimization goals will be as follows: CI ≥ 2.5 L/min/m2 and the SVV <10%. Sequential interventions used to reach the hemodynamic goals are regulated by a flow-chart provided in the study protocol. In Group 2 conventional static hemodynamic parameters (CVP, IBP) are evaluated to achieve an intraoperative MAP ≥ 70 mmHg with corrective actions (fluids, vasoactive agents) implemented according to the recommendations of good clinical practice and international guidelines. Both groups will receive standard induction immunosuppression according to our centre's practice as well as corticosteroid bolus (or two boluses if a dual kidney transplant was performed) before graft reperfusion. In the postoperative period all patients will be transferred to a dedicated post-surgical intensive care unit. The same standardized fluid therapy regimen will be adopted across both groups. Patient data will be prospectively collected, according to the study protocol, by designated personnel using a digital case report form.

SAMPLE SIZE CALCULATION AND STATISTICAL ANALYSIS. The investigators speculate that in order to detect a minimum reduction in the primary outcome of at least 18%, considering a power of 80% and a type I error of 5%, a total of 200 patients would be needed (100 per group). All results will be summarized in the text as means, unless differently stated each time with measures of variability expressed using mean and standard deviation. When reporting medians, measures of variability will be indicated as interquartile range, minimum value, and maximum value. Difference between population means will be obtained using the 2-sample t test; difference between population proportions will be obtained with the chi-square test and Fisher's exact test. Graft survival will be calculated from the date of kidney transplant to the date of last follow-up evaluation, graft loss, or patient death. P-values below or equal to 0.05 are considered as statistically significant.

Inclusion Criteria:

• age > 18 years,
• first single- or dual-kidney transplant from a deceased donor,
• absence of atrial fibrillation or other severe arrythmia,
• ASA (American Society of Anesthesiologists) class III-IV,
• presence of written expression of consent.

Exclusion Criteria:

• patients receiving a retransplant,
• patients receiving a combined liver-kidney transplant,
• patients receiving a transplant from a living donor .

The patients (individual participants) are prevented from having knowledge of the interventions assigned