EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 available at www.sciencedirect.com journal homepage: www.eu-openscience.europeanurology.com Renal Disease Robotic Versus Open Kidney Transplantation from Deceased Donors: A Prospective Observational Study q Riccardo Campi a,b,*,1, Alessio Pecoraro a,1, Vincenzo Li Marzi a, Agostino Tuccio c, Saverio Giancane a, Adriano Peris d, Calogero Lino Cirami e, Alberto Breda f,g, Graziano Vignolini a,2, Sergio Serni a,b,g,2 a Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy; b Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; c Unit of Urological Oncologic Minimally-Invasive Robotic Surgery and Andrology, University of Florence, Careggi Hospital, Florence, Italy; d Intensive Care Unit and Regional ECMO Referral Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; e Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, Italy; f Department of Urology, Fundació Puigvert, Autonoma University of Barcelona, Barcelona, Spain; g European Association of Urology (EAU) Robotic Urology Section (ERUS)—Robot-assisted Kidney Transplantation (RAKT) Working Group, the Netherlands Article info Abstract Article history: Background: While robot-assisted kidney transplantation (RAKT) from living Accepted March 5, 2022 donors has been shown to achieve favourable outcomes, there is a lack of evidence on the safety and efficacy of RAKT as compared with the gold standard open kidney Associate Editor: transplantation (OKT) in the setting of deceased donors, who represent the source M. Carmen Mir of most grafts worldwide. Objective: To compare the intraoperative, perioperative, and midterm outcomes of Keywords: RAKT versus OKT from donors after brain death (DBDs). Complications Design, setting, and participants: Data from consecutive patients undergoing RAKT Deceased donor Kidney or OKT from DBDs at a single academic centre between October 2017 and Renal function December 2020 were prospectively collected. Robotic Intervention: RAKT or OKT. Transplant Outcome measurements and statistical analysis: The primary outcomes were intraoperative adverse events, postoperative surgical complications, delayed graft function (DGF), and midterm functional outcomes. A multivariable logistic q Study collaborators: Paolo Barzaghi (Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy), Francesco Corti (Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy), Mauro Gacci (Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy), Simone Morselli (Unit of Urological Robotic Surgery and Renal Transplan- tation, University of Florence, Careggi Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy), Arcangelo Sebastianelli (Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy), Francesco Sessa (Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy), Pietro Spatafora (Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy). 1 These authors contributed equally to this work. 2 These authors shared senior authorship equally. * Corresponding author. Chirurgia Urologica Robotica Mini-Invasiva e dei Trapianti Renali, Azienda Ospedaliero-Universitaria Careggi, Viale San Luca, 50134 Firenze, Italy. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Largo Brambilla, 3, 50134 Firenze, Italy. Tel. +39 055 2758020; Fax: +39 0552758014. E-mail address: riccardo.campi@gmail.com (R. Campi). https://doi.org/10.1016/j.euros.2022.03.007 2666-1683/Ó 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 37 regression analysis assessed the independent predictors of DGF, trifecta, and suboptimal graft function (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m2) at the last follow-up. Results and limitations: Overall, 138 patients were included (117 [84.7%] OKTs and 21 [15.3%] RAKTs). The yearly proportion of RAKT ranged between 10% and 18% during the study period. The OKT and RAKT cohorts were comparable regarding all graft-related characteristics, while they differed regarding a few donor- and recipient-related factors. The median second warm ischaemic time, ureterovesical anastomosis time, postoperative complication rate, and eGFR trajectories did not differ significantly between the groups. A higher proportion of patients undergoing OKT experienced DGF; yet, at a median follow-up of 31 mo (interquartile range 19– 44), there was no difference between the groups regarding the dialysis-free and overall survival. At the multivariable analysis, donor- and/or recipient-related fac- tors, but not the surgical approach, were independent predictors of DGF, trifecta, and suboptimal graft function at the last follow-up. The study is limited by its non- randomised nature and the small sample size. Conclusions: Our study provides preliminary evidence supporting the noninferior- ity of RAKT from DBDs as compared with the gold standard OKT in carefully selected recipients. Patient summary: Kidney transplantation using kidneys from deceased donors is still being performed with an open surgical approach in most transplant centres worldwide. In fact, no study has compared the outcomes of open and minimally invasive (robotic) kidney transplantation from deceased donors. In this study, we evaluated whether robotic kidney transplantation using grafts from deceased donors was not inferior to open kidney transplantation regarding the intraoperative, postoperative, and midterm functional outcomes. We found that, in experienced hands and provided that there was a time-efficient organisation of the transplanta- tion pathway, robotic kidney transplantation from deceased donors was feasible and achieved noninferior outcomes as compared with open kidney transplantation. Ó 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative- commons.org/licenses/by-nc-nd/4.0/). 1. Introduction 2. Patients and methods 2.1. Patients and dataset Open kidney transplantation (OKT) is the gold standard treat- ment for patients with end-stage renal disease, providing bet- After ethical committee approval, data from consecutive patients under- ter survival and quality of life as compared with dialysis [1–3]. going RAKT or OKT from DBDs at our centre between October 2017 and Elective robot-assisted kidney transplantation (RAKT) December 2020 were prospectively collected in our institutional data- from living donors has been shown to achieve favourable base. A comprehensive overview of the steps required to develop our outcomes [4–9] and to have the potential to minimise sur- RAKT programme is reported in previous publications [11,12]. Patients gical morbidity as compared with OKT [10]. Nonetheless, who underwent RAKT or OKT from living donors or from donors after RAKT is still controversial and underutilised in the setting circulatory death were excluded from this study (Supplementary Fig. 1). DBDs were considered ‘‘expanded criteria donors’’ (ECDs) if they of deceased donors, who represent the most frequent were aged >60 or 50–59 yr with two of the following features: history source of grafts in most countries worldwide [3]. of hypertension, terminal serum creatinine 1.5 mg/dl, or death result- While being more demanding for transplant teams from ing from a cerebrovascular accident [3]. both technical and logistical standpoints [11], expanding The Chronic Kidney Disease Epidemiology Collaboration formula was the indications for RAKT to deceased donors is an unmet used to calculate estimated glomerular filtration rate (eGFR) in patients clinical need: a higher number of fragile and immunocom- aged <70 yr [13], while the Berlin Initiative Study formula was used for promised recipients could indeed benefit from minimally patients aged 70 yr [14]. invasive surgery. In this regard, the feasibility and prelimi- Cold ischaemia time (CIT) was defined as the time of cold storage, nary outcomes of RAKT from deceased donors has previ- while second warm ischaemic time (SWIT) as the time needed during ously been reported by our group [11,12]. However, to the construction of vascular anastomoses until revascularisation. For date, there is a lack of evidence on the comparative effec- RAKT, SWIT (also defined as ‘‘rewarming time’’ [5]) was defined as the tiveness of RAKT versus OKT in this context. time between graft insertion in the abdominal cavity and To fill this gap, we sought to compare the intraoperative, revascularisation. perioperative, and midterm functional outcomes of RAKT Intraoperative complications were reported according to the Intraop- versus OKT from donors after brain death (DBDs) over a 4- erative Adverse Incident Classification (EAUiaiC) by the European Asso- yr period. ciation of Urology (EAU) ad hoc Complications Guidelines Panel [15], 38 EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 while postoperative surgical complications were according to both the operating room staff are always available, if needed), (3) availability of modified Clavien-Dindo system [16] and the Comprehensive Complica- the robotic operating room (during weekdays, nights, and weekends), tion Index [17]. (4) CIT <20 h to achieve graft reperfusion within a <24 h time frame, Delayed graft function (DGF) was defined as the need of dialysis in and (5) no graft-related contraindications for RAKT during bench surgery the first postoperative week [3]. Trifecta was defined as the contempo- (mainly complex vascular anatomy requiring complex ex situ recon- rary achievement of the following outcomes: (1) no DGF, (2) no major struction and potentially multiple anastomoses). (Clavien-Dindo grade 3) postoperative surgical complications, (3) eGFR 30 ml/min/1.73 m2 at hospital discharge. 2.3. Surgical team for OKT and RAKT All recipients underwent computed tomography angiogram to assess their vascular anatomy and the potential presence of atherosclerotic pla- At our centre, OKTs were performed by four experienced urologic ques of iliac vessels. surgeons. Preoperative evaluation of donors, postoperative management of One of these surgeons (G.V.), experienced in both OKT and robotic recipients, and follow-up after RAKT/OKT were performed by our multi- urologic surgery (>1500 procedures), performed all RAKTs. At the begin- disciplinary transplant team according to established guidelines and our ning of his experience with RAKT from DBDs, the surgeon had already institutional protocol [2,18]. successfully performed six RAKTs [11]. Each of the four surgeons were on call for 1 d per week plus 1 week- 2.2. Decision-making strategy regarding selection of open versus end (Friday to Sunday) per month. As such, RAKT from DBDs was per- robotic surgical approach formed only if the kidney offer was made when the RAKT surgeon was on charge and all the above-mentioned criteria for RAKT (see Section 2.2) Selection criteria for RAKT changed over time [11,12]. Nowadays, after were met. the evaluation of graft suitability for transplantation by the Regional Transplant Authority and selection of the potential recipient, all the fol- 2.4. Surgical technique lowing criteria must be met to perform RAKT (Fig. 1): (1) absence of recipient-related contraindications for RAKT (currently represented by A detailed step-by-step description of our surgical technique for RAKT recipient age <18 yr, absolute contraindication for robotic surgery, mul- from deceased donors is reported in previous publications [11,12] and tiple previous major abdominal surgeries, and severe atherosclerotic pla- graphically depicted in Figs. 2–4. During bench surgery, the graft is care- ques at the level of iliac vessels), (2) availability of the robotic transplant fully prepared by the transplant surgeon and placed in a gauze jacket. In team (mainly according to the surgeon on call; assistant surgeons and case of multiple vessels, the surgeon may use different techniques to Fig. 1 – Flowchart showing the decision-making strategy regarding selection of the open versus robotic surgical approach for kidney transplantation from donors after brain death (DBDs) at our centre. Once the kidney offer has been received, the kidney has been evaluated for its suitability for transplantation by the Regional Transplant Authority (RTA; Centro Regionale Allocazione Organi e Tessuti [CRAOT]), and selection of the potential recipient has been finalised, specific criteria must be met to perform robot-assisted kidney transplantation (RAKT). If one or more criteria are not respected, then open kidney transplantation (OKT) is performed. In particular, there must be no recipient-related contraindications for RAKT (currently represented by recipient age <18 yr, absolute contraindication for robotic surgery, multiple previous major abdominal surgeries, and severe atherosclerotic plaques at the level of iliac vessels), the robotic transplant team and operating room staff must be available (even during the night or the weekends), the robotic operating room must be available, the cold ischaemia time (CIT) must be <20 h to allow a safe graft reperfusion within a <24 h time frame, and finally, no graft-related contraindications for RAKT must be seen at the time of bench surgery (ie, mainly complex vascular anatomy requiring complex ex situ reconstruction and potentially multiple anastomoses). EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 39 Fig. 2 – (A) Overview of the main steps of bench surgery, (B) port placement, and (C) introduction of the graft into the abdominal cavity according to the University of Florence technique for robot-assisted kidney transplantation (RAKT). (A) If severe atherosclerotic plaques are noted on the aortic patch at the level of the graft artery ostium, the surgeon may decide to remove it and perform the arterial anastomosis without the patch. (B) Port placement for RAKT from deceased donors. RAKT was performed following the principles of the Vattikuti-Medanta technique [4] using either the da Vinci Si or the Xi robotic platform in a four-arm configuration, with a 0° lens and a 20° Trendelenburg tilt. Pneumoperitoneum pressure was set at 8–10 mmHg and maintained constant through the use of the Airseal system. A Pfannenstiel incision is used to introduce the graft through the GelPoint device or the Alexis system. (C) External and intraoperative view of the graft before and after its introduction into the peritoneal cavity during RAKT. In this specific case, the aortic patch was removed by the surgeon during bench surgery. During bench surgery, the anterior margin of the graft vein is reshaped by cutting away a slice of venous tissue to improve visualisation of its posterior margin during the subsequent venous anastomosis. In case of right-sided grafts, an inferior vena cava patch is performed to increase the length of the graft renal vein. The graft is finally placed in a gauze jacket filled with ice, with the renal artery fixed to the gauze with a landmark stich. In case of RAKT, a double-J stent is routinely placed at the time of bench surgery to facilitate subsequent ureterovesical anastomosis. A = assistant port; C = camera port; G = graft; IA = (external) iliac artery; IV = (external) iliac vein; R = robotic port. reconstruct the graft vessels aiming to perform a single anastomosis Vascular anastomoses were completed in an end-to-side fashion to [19]. For RAKT, a double-J stent is routinely preplaced at the time of the external iliac vessels using a 5-0 or 6-0 GORE-TEX suture (Gore Med- bench surgery. If severe atherosclerotic plaques are noted on the aortic ical, Flagstaff, AZ, USA) on a CV-6 TTc-9 needle. patch at the level of the graft artery ostium, the surgeon may decide to Specific technical nuances were introduced by our group [11,12]. remove it and perform the arterial anastomosis without the patch, mir- First, a Pfannenstiel incision is used to introduce the graft through the roring RAKT from living donors (Fig. 2A). GelPoint device or the Alexis system (Fig. 2B). Second, two half running OKT was performed following established principles [3], with a Gib- sutures using two (rather than one) threads are used for the arterial son or fascial incision usually over the right iliac fossa. After creation of anastomosis. Lastly, intraoperative FireFly fluorescence vascular imaging an extraperitoneal pouch, vascular anastomoses are completed in an with indocyanine green is employed to check for ureteral and graft end-to-side fashion between the graft and the external iliac vessels using reperfusion (if the da Vinci Xi robotic platform is used; Fig. 4) [20]. two running, nonabsorbable, 5-0 or 6-0 polypropylene sutures. After The ureterovesical anastomosis is completed with two running absorb- completion of the anastomoses, the graft is placed in the extraperitoneal able sutures according to a modified Lich-Gregoire technique over the pouch and evaluated for adequate reperfusion (colour, turgor, and intra- preplaced double-J stent (Fig. 4). operative ultrasound, if needed). The ureterovesical anastomosis is made with interrupted or running absorbable sutures according to a modified 2.5. Study objectives Lich-Gregoire technique over a double-J stent creating an antirefluxing mechanism. The primary objective of the study was to compare the perioperative and RAKT was performed following the principles of the Vattikuti- midterm results of RAKT versus OKT from DBDs. Specifically, the out- Medanta technique [4] using either the da Vinci Si or the Xi robotic plat- come measures evaluated were the following: (1) intraoperative adverse form (Intuitive Surgical Inc., Sunnyvale, CA, USA) in a four-arm configu- events; (2) early postoperative outcomes, including the length of hospi- ration, with a 0° lens and a 20° Trendelenburg tilt. Pneumoperitoneum talisation (LOH), postoperative complications, and DGF; and (3) midterm pressure was set at 8–10 mmHg and maintained constant through the outcomes, including patient and graft survival, reintervention rate, hos- use of the Airseal system (Fig. 2 and 3). pital readmission, and eGFR trajectories over time. 40 EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 Fig. 3 – Intraoperative snapshots showing the main phases of the (A) venous and (B) arterial anastomoses during robot-assisted kidney transplantation from donors after brain death (Figs. 2 and 3). Vascular anastomoses are completed in an end-to-side fashion to the external iliac vessels using a 5-0 or 6-0 GORE- TEX suture (Gore Medical) on a CV-6 TTc-9 needle, as described previously [11,12]. For the arterial anastomosis, two half running sutures using two different threads are used, due to the thicker wall of both graft and recipient arteries. The arterial anastomosis may be performed without or with (*) the aortic Carrel’s patch. The secondary objective of the study was to assess the potential 18% in 2018 and remained constant thereafter. The most fre- impact of surgical approach on DGF, trifecta, and optimal renal function quent reason preventing the performance of RAKT was the (eGFR 45 ml/min/1.73 m2) at the last follow-up. unavailability of the robotic team (101/117 cases [86%]; Supplementary Fig. 1). The other reasons to perform OKT 2.6. Statistical analysis despite the availability of the RAKT team were as the learn- ing curve of the RAKT surgeon (4%), potentially longer CIT Statistical analyses were performed and reported according to estab- (2%), unavailability of the robotic operating room (3%), and lished guidelines [21]. specific recipient- or graft-related contraindications (5%). Descriptive statistics were obtained reporting medians and The baseline donor-, recipient-, and graft-related charac- interquartile ranges (IQRs) for continuous variables, awhile numbers and proportions were used for categorical variables. teristics in the RAKT and OKT cohorts are shown in Supple- The characteristics of the baseline donors, recipients, and grafts were mentary Table 1. The median donor age (55 vs 49 yr, p = 0.2), compared between the OKT and the RAKT groups using the Kruskal- median donor body mass index (BMI; 25.1 vs 22.5, p = 0.01) Wallis and chi-square tests, as appropriate. and the proportion of expanded criteria donors (49.6% vs Univariable and multivariable logistic regression analyses were per- 28.6%, p = 0.07) were higher in the OKT cohort. While the formed to assess the independent predictors of the main study outcomes study groups were comparable regarding recipients’ median among donor-, graft-, recipient-, and surgery-related factors. age, gender, and median BMI, the recipients’ comorbidity Statistical analyses were performed using SPSS v.26 (IBM SPSS Statis- burden was higher in the OKT group (median American Soci- tics for Mac; IBM Corp., Armonk, NY, USA). All tests were two sided, with ety of Anesthesiologists score 3 vs 2, p < 0.001). Nonetheless, a significance set at p < 0.05. the proportion of recipients with a higher comorbidity bur- den (Charlson Comorbidity Index 3) was similar across the 3. Results two groups (17.1% vs 19.0%, p = 0.8). A significantly higher proportion of recipients receiving OKT had undergone previ- ous major abdominal surgery (52.1% vs 28.6%, p = 0.047) or a 3.1. Characteristics of the study cohorts previous kidney transplantation (12.8% vs 4.8%, p = 0.3). Overall, 199 kidney transplantations were performed during Lastly, recipients in the OKT group were less likely to be the study period. Of these, 138 (69.3%) were from DBDs and pre-emptive (5.1% vs 38.1%, p < 0.001) and had longer med- were included in the analytic cohort (117 [84.7%)] OKTs and ian times on dialysis (32 vs 9 mo, p < 0.001). The OKT and 21 [15.3%] RAKTs; Supplementary Fig. 1). The yearly propor- RAKT cohorts were comparable regarding all graft-related tion of RAKT from DBDs was 10% in 2017, which increased to characteristics (Supplementary Table 1). EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 41 Fig. 4 – Intraoperative snapshots showing the last operative steps of robot-assisted kidney transplantation (RAKT) from donors after brain death (DBDs) according to the University of Florence technique. After completion of the vascular anastomosis, (A) the graft reperfusion is checked using intraoperative fluorescence vascular imaging with indocyanine green. Then, (B) the previously prepared extraperitoneal pouch is closed with a running suture. (C) Intraoperative duplex ultrasound may be used to further check graft reperfusion. (D) Before the ureterovesical anastomosis, the ureteral reperfusion is checked using intraoperative fluorescence vascular imaging with indocyanine green. Then, (E) the ureterovesical anastomosis is completed with two running absorbable sutures according to a modified Lich-Gregoire technique over the preplaced double-J stent (steps 1–6). FVI = fluorescence vascular imaging. 3.2. Intraoperative outcomes There was no significant difference between the study groups in the eGFR trajectories after transplantation, while All RAKTs were completed successfully, with no need of a higher proportion of patients undergoing OKT experi- open conversion. enced DGF (27.4% vs 9.5%, p = 0.08). Overall, the trifecta The median overall operative time (incision to closure), was achieved by 52.2% of patients (66.7% vs 49.6% in the SWIT, and ureterovesical anastomosis time did not differ RAKT vs OKT group, p = 0.2). significantly between RAKT and OKT (210 vs 205 min, At the multivariable analysis (Table 2), donor BMI (odds p = 0.2; 47 vs 48 min, p = 0.2; and 15 vs 18 min, p = 0.2, ratio [OR]: 1.21; 95% confidence interval [CI]: 1.07–1.37, respectively). p = 0.002) and time of pretransplantation dialysis (OR: Intraoperative adverse events were recorded in ten 1.09; 95% CI: 1.03–1.16, p = 0.003) were the only significant patients (7.2%), of whom nine underwent OKT and one predictors of DGF in our cohort. Similarly, type of DBDs (OR RAKT (all EAUiaiC grade 0–1). for standard donor vs ECD: 2.14; 95% CI: 1.10–5.00, p = 0.038) and time of pretransplantation dialysis (OR: 3.3. Postoperative and early functional outcomes 0.93; 95% CI: 0.87–0.98, p = 0.011) were the only indepen- An overview of the early postoperative outcomes after RAKT dent predictors of trifecta achievement. versus OKT is provided in Table 1. There were no significant The median LOH was 13 d in both groups. At the multi- differences between RAKT and OKT regarding the overall variable analysis, the only independent predictors of LOH and major postoperative complications rates, as well as 2 wk (n = 70/138 patients; 50.7%) were the need for post- the median Comprehensive Complication Index. The pro- operative blood transfusions, occurrence of major surgical portion of patients requiring perioperative blood transfu- complications, and DGF (Supplementary Table 2). sions was significantly lower in the RAKT cohort (14.3% vs There was no statistically significant difference in the 22.2%, p = 0.008), as well as the proportion of patients proportion of patients experiencing major (Clavien-Dindo requiring opioids treatment for postoperative pain during grade 3) surgical complications and/or DGF between the hospitalisation (0% vs 7.7%). open (n = 42/117, 35.9%) and robotic (n = 5/21, 23.8%) groups Seven (5.0%) patients required graft nephrectomy during (p = 0.2). the early postoperative period (of whom six [5.1%] were in There was no difference in median LOH between OKT and the OKT group and one [4.8%] in the RAKT group). RAKT both in the cohort of patients not experiencing major 42 EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 Table 1 – Intraoperative, postoperative, and midterm functional outcomes after robot-assisted kidney transplantation (RAKT) versus open kidney transplantation (OKT) in our study Overall cohort OKT (n = 117) RAKT (n = 21) p (n = 138) value Intraoperative outcomes Intraoperative complications, n (%) 10 (7.2) 9 (7.6) 1 (4.8) 0.2 EAUiaiC grade 0 5 5 0 EAUiaiC grade 1 5 4 1 Operative time (incision to closure; min), median (IQR) 208 (180–240) 205 (180–230) 210 (185–241) 0.2 Console time (for RAKT; min), median (IQR) – – 180 (150–202) – Arterial anastomosis time (min), median (IQR) 21 (17–26) 22 (17–29) 18 (15–21) 0.008 Vein anastomosis time (min), median (IQR) 23 (18–28) 24 (18–32) 18 (16–22) 0.007 Ureterovesical anastomosis (min), median (IQR) 18 (15–20) 18 (15–20) 15 (12–21) 0.2 Second warm ischaemic time (min), median (IQR) 48 (42–55) 48 (43–55) 47 (41–52) 0.2 Early postoperative outcomes (during hospitalisation) Overall length of hospitalisation (d), median (IQR) 13 (11–18) 13 (11–18) 13 (10–18) 0.5 Highest grade postoperative surgical complication (according to the 0.6 Clavien-Dindo classification), n (%) Grade 0 46 (33.3) 40 (34.2) 6 (28.6) Grade 1 4 (2.9) 4 (3.4) 0 (0.0) Grade 2 65 (47.1) 53 (45.3) 12 (57.1) Grade 3a 9 (6.5) 7 (6.0) 2 (9.5) Grade 3b Overall 11 (8.0) 10 (8.5) 1 (4.8) Graft nephrectomy (thrombosis) 6 (4.3) 5 (4.3) 1 (4.8) (3 venous thrombosis) (venous thrombosis) (2 arterial thrombosis) Graft nephrectomy (haemorrhagic complications) 1 (0.7) 1 (0.8) 0 (0) Endoscopic reintervention (double-J stent misplacement) 1 (0.7) 1 (0.8) 0 (0) Endoscopic placement of a double-J stent for urinary fistula 1 (0.7) 1 (0.8) 0 (0) Reintervention for bleeding causing graft compression 2 (1.4) 2 (1.7) 0 (0) Grade 4a 2 (1.4) 1 (0.9) 1 (4.8) Grade 4b 0 (0.0) 0 (0.0) 0 (0.0) Grade 5 1 (0.7) 1 (0.9) 0 (0.0) (sepsis with multiorgan failure) Patients requiring perioperative blood transfusions, n (%) 29 (21.0) 26 (22.2) 3 (14.3) 0.008 Major postoperative surgical complication (highest grade 3 23 (16.6) 20 (17.1) 3 (14.3) 0.7 according to the Clavien-Dindo classification), n (%) Comprehensive Complication Index, median (IQR) 20.9 (0.0–29.6) 20.9 (0.0–29.6) 20.9 (0.0–29.6) 0.8 Patients requiring opioid treatment for postoperative pain, n (%) 9 (6.5) 9 (7.7) 0 (0) 0.1 Early functional outcomes (during hospitalisation) Delayed graft function, n (%) 34 (24.6) 32 (27.4) 2 (9.5) 0.08 eGFR (ml/min/1.73 m2), median (IQR) POD 1 7.5 (6–10) 7.2 (5.7–9) 8.5 (7.5–14) 0.7 POD 3 10.2 (7.1–24) 10.6 (6.8–23.4) 10 (8–35) 0.6 POD 7 25.3 (11–48.1) 25 (11–48.6) 28.2 (12.7–40.4) 0.7 At hospital discharge 39.7 (23.5–56.6) 39.4 (22.7–56) 41 (29.8–59.2) 0.3 Trifecta, n (%) 72 (52.2) 58 (49.6) 14 (66.7) 0.2 Follow-up outcomes Follow-up (mo), median (IQR) 31 (19–44) 31 (20–44) 27 (16–42) 0.5 Graft nephrectomy, n (%) 8 (5.8) 7 (6.0) 1 (5.0) 0.8 Causes detailed above Cause detailed (n = 6) + chronic rejection (n = 1) above Patients alive at last follow-up, n (%) 133 (96.4) 113 (96.6) 20 (95.2) 0.7 Patients who were alive and dialysis free (n = 133), n (%) 124 (93.2) 105 (93.0) 19 (95.0) 0.7 Hospital readmission (at least one episode) after KT, n (%) 71 (51.4) 61 (52.1) 10 (47.6) 0.7 KT-related reinterventions, n (%) 9 (6.5) 6 (5.1) 2 (9.5) 0.6 TRAS requiring PTCA + stenting 5 3 2 Lymphoceles requiring percutaneous drainage 2 2 0 Ureteral reimplantation 1 1 0 Ureteral stenting 1 1 0 eGFR at last follow-up (ml/min/1.73 m2), median (IQR) 53.5 (38.0–68.0) 51.0 (37.5–64.3) 68.7 (46.0–81.0) 0.042 EAUiaiC = Intraoperative Adverse Incident Classification by the European Association of Urology; eGFR = estimated glomerular filtration rate; IQR = interquartile range; KT = kidney transplantation; POD = = postoperative day; PTCA = percutaneous transluminal coronary angioplasty; TRAS = transplant renal artery stenosis. surgical complications and/or DGF (12 d [IQR 10–16] vs 13 d 3.4. Follow-up outcomes [IQR 9–15], p = 0.9) and in the cohort of patients experienc- ing major surgical complications and/or DGF (35.9% of At a median follow-up of 31 mo (IQR 19–44), patient sur- patients in the OKT group and 23.8% of patients in the RAKT vival and dialysis-free survival were comparable between group, p = 0.2; 17 d [IQR 14–23] vs 18 d [IQR 16–22], p = 0.9). the RAKT and OKT groups (Table 1). Similarly, the readmis- Table 2 – Univariable and multivariable logistic regression models assessing the independent predictors of delayed graft function (DGF), trifecta, and optimal graft function (estimated glomerular filtration rate 45 ml/min/1.73 m2) at last follow-up among donor-, recipient-, graft-, and surgery-related factors Delayed graft function Trifecta eGFR 45 ml/min/73 m2 at last follow-up Univariable a. Multivariable a. Univariable a. Multivariable a. Univariable a. Multivariable a. OR (95% CI) OR (95% CI) p value OR (95% CI) OR (95% CI) p value OR (95% CI) OR (95% CI) p value EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 Donor characteristics Age (yr) 1.02 (0.99–1.05) – – 0.97 (0.95–0.99) – – 0.96 (0.93–0.99) – – BMI (kg/m2) 1.20 (1.08–1.35) 1.21 (1.07–1.37) 0.002 0.92 (0.84–1.00) 0.93(0.85–1.02) 0.1 0.94 (0.86–1.02) – – Gender (male vs female) 0.96 (0.44–2.09) – – 1.12 (0.62–2.37) – – 0.88 (0.41–1.87) – – No history of hypertension 0.45 (0.20–1.02) – – 1.92 (0.90–4.07) – – 1.73 (0.75–4.04) – – SCD vs ECD 0.51 (0.23–1.13) 0.67 (0.26–1.68) 0.4 2.82 (1.41–5.64) 2.14(1.10–5.00) 0.038 3.10 (1.42–6.79) 2.54 (1.09–6.52) 0.04 eGFR (ml/min/1.73 m2) 0.99 (0.97–1.01) 0.98 (0.97–1.01) 0.2 1.00 (0.99–1.01) – – 1.00 (0.99–1.01) – – Recipient characteristics Recipient age (yr) 1.02 (0.98–1.05) – – 0.96 (0.94–0.99) 0.98(0.94–1.02) 0.4 0.97 (0.93–0.99) 0.99 (0.95–1.03) 0.6 Gender (male vs female) 1.18 (0.53–2.62) – – 0.83 (0.42–1.67) – – 1.31 (0.61–2.73) – – Recipient BMI (kg/m2) 0.99 (0.98–1.01) – – 1.00 (0.99–1.01) – – 1.00 (0.98–1.03) – – No diabetes mellitus 0.83 (0.27–2.52) – – 0.51 (0.18–1.44) – – 1.34 (0.41–4.39) – – ASA score (continuous) 1.68 (0.83–3.40) – – 0.87 (0.50–1.49) – – 0.73 (0.39–1.36) – – No previous KT 0.67 (0.22–2.13) – – 1.49 (0.52–4.26) – – 2.26 (0.68–7.53) – – Recipient CCI (continuous) 1.24 (0.72–2.12) 1.07 (0.65–1.77) – – 0.85 (0.49–1.84) – – Pre-emptive recipient NA* – – 14.10 (1.79–111.13) – – 3.21 (0.68–15.09) – – Duration of dialysis (6 mo) 1.08 (1.02–1.14) 1.09 (1.03–1.16) 0.003 0.92 (0.87–0.98) 0.93 (0.87–0.98) 0.011 0.95 (0.90–1.02) 0.96 (0.90–1.03) 0.3 Graft characteristics Cold ischaemia time (h) 1.01 (0.93–1.09) 0.97 (0.88–1.07) 0.6 0.95 (0.87–1.01) 0.97(0.89–1.05) 0.5 0.99 (0.91–1.07) 1.01 (0.93–1.10) 0.8 Right- vs left-sided graft 0.92 (0.43–2.01) – – 1.08 (0.55–2.12) – – 0.68 (0.32–1.47) – – Karpinsky score (at biopsy) 1.20 (0.72–2.00) – – 1.12 (0.71–1.73) – – 1–09 (0.68–1.72) – – No multiple graft vessels 0.80 (0.33–1.89) – – 0.98 (0.46–2.11) – – 1.27 (0.54–3.02) – – Surgery-related factors Open vs robotic approach 3.57 (0.78–16.23) 2.12 (0.39–11.56) 0.4 0.50 (0.18–1.32) 0.84(0.28–2.49) 0.7 0.50 (0.16–1.63) 0.74 (0.21–2.57) 0.6 Second warm ischaemic time (min) 0.97 (0.92–1.04) – – 1.06 (0.92–1.07) – – 0.99 (0.95–1.03) – – Overall operative time (min) 1.01 (0.99–1.01) – – 0.99 (0.98–1.02) – – 1.00 (0.99–1.01) – – Postoperative factors No delayed graft function – – 2.90 (1.20–6.98) 2.25 (0.89–5.67) 0.08 a. = analysis; ASA = American Society of Anesthesiologists; BMI = body mass index; CCI = Charlson Comorbidity Index; CI = confidence interval; ECD = expanded criteria donor; eGFR = estimated glomerular filtration rate; KT = kidney transplantation; NA = not available; OR = odds ratio; SCD = standard criteria donor. 43 44 EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 sion and reintervention rates were comparable. The median between RAKT and OKT. This finding should be interpreted eGFR at the last follow-up was significantly higher among in light of several factors as well as our hospital policies. As RAKT recipients (68.7 vs 51.0 ml/min/1.73 m2, p = 0.042). in France and Spain [27,28], the characteristics of the Italian At the multivariable analysis, surgical approach did not public health system, greater acceptance of older/comorbid influence the risk of suboptimal graft function at the last recipients, increasing proportion of ECDs, and absence of follow-up: donor type (OR for standard donor vs ECD: ambulatory facilities may explain the longer LOH at our 2.54; 95% CI: 1.09–6.52, p = 0.04) was the only significant centre than that in other countries such as the USA [29]. predictor of eGFR 45 ml/min/1.73 m2 at the last follow- Moreover, the early hospital readmission rate is a signifi- up (Table 2). cant quality metric at our centre, leading to cautious early hospital discharge. Lastly, as in other European countries 4. Discussion [27,28], nephrologists are responsible for postoperative care of recipients at our transplant centre and take decisions During the past decade, minimally invasive surgery has regarding hospital discharge. Further research is needed to increasingly permeated several fields, especially urology assess the differential impact of surgical approach, [22]. The widespread adoption of robotics worldwide has provider-related factors, healthcare context, and enhanced led to an increasing body of evidence supporting its nonin- recovery after surgery protocols on LOH, unplanned read- feriority to open surgery and its benefits for both surgeons missions, and costs of kidney transplantation [30]. and patients for selected interventions [23,24]. At the multivariable analysis (Table 2), surgical approach The transplantation community has been rather resis- was not found to be an independent predictor of DGF, tri- tant to such change, and OKT still remains the gold standard fecta, and ‘‘favourable’’ graft function (eGFR 45 ml/min) approach at most centres worldwide [2,3]. at a median follow-up of >2 yr; these outcomes were influ- Notably, in recent years, several groups have developed enced only by specific donor- and/or recipient-related and standardised the technique of RAKT, aiming to reduce characteristics. the morbidity of kidney transplantation [4–6,8–12,25]. Despite their novelty, our findings need to be interpreted Yet, a vast majority of RAKTs are elective procedures from with caution. In fact, several caveats and limitations could living donors, performed at a few referral centres in selected have influenced the study results. First, this is a prospective countries [26]. Therefore, there is a lack of evidence on the nonrandomised study with a relatively small sample size: as safety and outcomes of RAKT in the broader and much more such, the risk of selection bias and residual confounding complex scenario of deceased donors, who represent the cannot be ruled out. Of note, the OKT and RAKT cohorts predominant source of grafts worldwide. Of note, RAKT were comparable regarding all graft-related characteristics, from deceased donors can be referred as an urgent robotic but a few important clinical variables were not balanced procedure, increasing the challenges for transplant teams between the study groups (Supplementary Table 1). More- from both technical and logistical standpoints [11]. over, although the primary reason to perform OKT was the To the best of our knowledge, this is the first study that unavailability of the robotic surgical team, even when provides preliminary evidence supporting the noninferiority potentially feasible, a careful patient selection was pursued of RAKT as compared with OKT from deceased donors using (Supplementary Fig. 1). For instance, patients with standardised outcome metrics. Our findings provide key moderate-to-severe atheromatosis of the aortoiliac axis clinical messages for urologists and transplant surgeons. might have been more likely to undergo OKT despite the First, our study confirms that, despite the higher logisti- logistical feasibility for RAKT. Unfortunately, our dataset cal complexity, RAKT from DBDs can be performed success- lacked granular information on aortoiliac atheromatosis, fully, as reported previously [11,12]. precluding any analysis on its impact on recipient selection Second, our study showed that RAKT from DBDs can for RAKT versus OKT. achieve noninferior intraoperative, perioperative, and mid- Taken together, the differences in baseline donor- and- term functional outcomes as compared with OKT in well- recipient related characteristics could explain the worse selected recipients. Following established surgical princi- functional outcomes observed after OKT, ultimately making ples [4–6], no major intraoperative adverse events were our findings hypothesis generating. While propensity-score recorded during RAKT, and both median CIT and SWIT were matching techniques might have at least partially overcome comparable with those of the OKT counterpart. The postop- this limitation, they could not be employed given the small erative morbidity profiles of RAKT and OKT from DBDs were sample size of our analytic cohort. Second, OKT was per- also similar in our preliminary experience. Moreover, the formed by four different surgeons, and the results of RAKT minimally invasive approach of RAKT led to a lower propor- might still be sensitive to a learning curve effect [8]; yet, tion of recipients requiring perioperative blood transfusions due to the limited sample size, we could not formally eval- or treatment with opioids for postoperative pain (Table 1). uate the extent to which a surgeon’s experience and skills Confirming previous prospective data in the setting of living might have modulated intra- and postoperative outcomes. donation [5,6,10], we did not record any case of symp- Lastly, our study is limited by a relatively short follow-up tomatic lymphocele requiring percutaneous drainage and and a lack of data on patient-reported outcomes as well as wound complication among patients undergoing RAKT from the cost effectiveness of RAKT versus OKT. Considering the DBDs. Notably, the median LOH after kidney transplanta- need for time-efficient logistics and previous experience in tion in our study (comparable with the average LOH RAKT, whether our findings could be generalisable to other reported in other European countries [27,28]) was similar transplant centres remains unknown. EUROPEAN UROLOGY OPEN SCIENCE 39 (2022) 36–46 45 Acknowledging these limitations and recognising the [2] Rodríguez Faba O, Boissier R, Budde K, et al. European Association of Urology guidelines on renal transplantation: update 2018. Eur Urol challenges for conducting randomised-controlled trials in Focus 2018;4:208–15. this field [31], our study adds significant novel data to the [3] Figueiredo A, Lledo-Garcıa E. European textbook on kidney kidney transplantation literature and provides key insights transplantation (ESTU-EAU), ed. 1. Arnhem, The Netherlands: The into foster clinical implementation of RAKT in the setting EAU Section of Transplantation Urology, European Association of Urology; 2017. of deceased donors as well as a foundation for significant [4] Menon M, Sood A, Bhandari M, et al. Robotic kidney transplantation further research. with regional hypothermia: a step-by-step description of the Larger multicentre prospective studies are indeed war- Vattikuti Urology Institute-Medanta Technique (IDEAL Phase 2a). ranted to (1) confirm the feasibility and safety of RAKT from Eur Urol 2014;65:991–1000. [5] Breda A, Territo A, Gausa L, et al. Robot-assisted kidney DBDs in other healthcare contexts, (2) define the best indi- transplantation: the European experience. Eur Urol 2018;73:273–81. cations and limits of RAKT from deceased donors, (3) estab- [6] Musquera M, Peri L, Ajami T, et al. Robot-assisted kidney lish RAKT-specific modular training curricula to increase the transplantation: update from the European Robotic Urology Section (ERUS) series. BJU Int 2021;127:222–8. number of surgical teams that may offer minimally invasive [7] Wagenaar S, Nederhoed JH, Hoksbergen AWJ, Bonjer HJ, Wisselink kidney transplantation, and (4) develop a framework to pro- W, van Ramshorst GH. Minimally invasive, laparoscopic, and robotic- mote RAKT at a higher number of transplant centres assisted techniques versus open techniques for kidney transplant worldwide. recipients: a systematic review. Eur Urol 2017;72:205–17. [8] Gallioli A, Territo A, Boissier R, et al. Learning curve in robot- assisted kidney transplantation: results from the European Robotic 5. Conclusions Urological Society Working Group. Eur Urol 2020;78:239–47. [9] Tzvetanov IG, Spaggiari M, Tulla KA, et al. Robotic kidney transplantation in the obese patient: 10-year experience from a Our study provides preliminary evidence supporting the single center. Am J Transplant 2020;20:430–40. noninferiority of RAKT from deceased donors as compared [10] Ahlawat R, Sood A, Jeong W, et al. Robotic kidney transplantation with the gold standard OKT in carefully selected recipients. with regional hypothermia versus open kidney transplantation for Larger multicentre studies with longer follow-up are patients with end stage renal disease: an ideal stage 2B study. J Urol 2021;205:595–602. needed to confirm our findings and to define the best indi- [11] Vignolini G, Campi R, Sessa F, et al. Development of a robot-assisted cations and limits of robotics in this clinical scenario. kidney transplantation programme from deceased donors in a referral academic centre: technical nuances and preliminary results. BJU Int 2019;123:474–84. Author contributions: Riccardo Campi had full access to all the data in [12] Vignolini G, Greco I, Sessa F, et al. The University of Florence the study and takes responsibility for the integrity of the data and the technique for robot-assisted kidney transplantation: 3-year experience. Front Surg 2020;7:583798. accuracy of the data analysis. [13] Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604–12. Study concept and design: Campi, Serni, Vignolini. [14] Schaeffner ES, van der Giet M, Gaedeke J, et al. The Berlin initiative Acquisition of data: Pecoraro, Li Marzi, Tuccio, Giancane, Peris, Cirami. study: the methodology of exploring kidney function in the elderly by combining a longitudinal and cross-sectional approach. Eur J Analysis and interpretation of data: Campi, Pecoraro. Epidemiol 2010;25:203–10. Drafting of the manuscript: Campi. [15] Biyani CS, Pecanka J, Rouprêt M, Jensen JB, Mitropoulos D. Critical revision of the manuscript for important intellectual content: Peco- Intraoperative Adverse Incident Classification (EAUiaiC) by the raro, Li Marzi, Tuccio, Giancane, Peris Cirami, Breda, Vignolini, Serni. European Association of Urology ad hoc Complications Guidelines Statistical analysis: Campi, Pecoraro. Panel. Eur Urol 2020;77:601–10. [16] Dindo D, Demartines N, Clavien PA. Classification of surgical Obtaining funding: None. complications: a new proposal with evaluation in a cohort of Administrative, technical, or material support: None. 6336 patients and results of a survey. Ann Surg 2004;240:205–13. Supervision: Serni. [17] Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The Other: None. comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg 2013;258:1–7. [18] Li Marzi V, Campi R, Sessa F, et al. Standardized duplex ultrasound- Financial disclosures: Riccardo Campi certifies that all conflicts of inter- based protocol for early diagnosis of transplant renal artery est, including specific financial interests and relationships and affiliations stenosis: results of a single institution retrospective cohort study. Biomed Res Int 2018;2018:2580181. relevant to the subject matter or materials discussed in the manuscript [19] Siena G, Campi R, Decaestecker K, et al. Robot-assisted kidney (eg, employment/affiliation, grants or funding, consultancies, honoraria, transplantation with regional hypothermia using grafts with stock ownership or options, expert testimony, royalties, or patents filed, multiple vessels after extracorporeal vascular reconstruction: received, or pending), are the following: None. results from the European Association of Urology Robotic Urology Section Working Group. Eur Urol Focus 2018;4:175–84. [20] Cacciamani GE, Shakir A, Tafuri A, et al. Best practices in near- Funding/Support and role of the sponsor: None. infrared fluorescence imaging with indocyanine green (NIRF/ICG)- guided robotic urologic surgery: a systematic review-based expert consensus. World J Urol 2020;38:883–96. Appendix A. Supplementary data [21] Assel M, Sjoberg D, Elders A, et al. Guidelines for reporting of statistics for clinical research in urology. Eur Urol 2019;75:358–67. Supplementary data to this article can be found online at [22] Almujalhem A, Rha K. Surgical robotic systems: what we have now? A urological perspective. BJUI Compass 2020;1:152–9. https://doi.org/10.1016/j.euros.2022.03.007. [23] Cacciamani GE, Gill K, Gill IS. Robotic versus open urological oncological surgery: study protocol of a systematic review and References meta-analysis. BMJ Open 2020;10:e036609. [24] Gill I, Cacciamani G. The changing face of urologic oncologic surgery [1] Hariharan S, Israni AK, Danovitch G. 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