Project 2

2.1 History and background

2.2 Operative technique

2.3 Results

After reporting a single center experience on 17 cases of RAKT from living donation, the European Experience in RAKT was published in 2018. One hundred twenty cases were prospectively collected in eight centers across Europe. The authors demonstrated the low complication rate (at 1 month follow-up) while maintaining excellent graft function (median eGFR at 30 days was 58 ml/min) and cosmetic results (Figure 8). Three cases of graft loss due to arterial thrombosis during the first postoperative week were reported in these series (2.5%). This complication might be associated with technical errors during the learning curve. Territo et al. demonstrated that the functional results at 1-year follow-up were not statistically different from the functional results at 1-month follow-up. The complication rate remained low. To date, there are no studies available comparing RAKT with the conventional open approach. However, an increasing body of evidence confirms that RAKT is at least non-inferior to open KT regarding both patient and graft survival.

3.1 Background

The vast majority of RAKT worldwide has been performed from living donors, raising concerns regarding the generalizability of RAKT outcomes in the broader and more challenging scenario of deceased donors.

While it has been shown that the learning curve for elective RAKT (i.e., living donor RAKT) may be minimal for surgeons with extensive experience in robotic surgery (regardless of their background in open KT) , RAKT from deceased donors has unique technical and logistical challenges. Indeed, due to the timeframe of organ preservation, it can be considered an unforeseeable “emergency” robotic procedure, which requires a structured multidisciplinary framework.

3.2 Development of a structured RAKT program from deceased donors

To fill this gap and move the field forward, the University of Florence group has recently developed a RAKT program from deceased donors aiming to safely and progressively increase the pool of patients who may benefit from minimally invasive KT.

The cornerstones of this program are as follows: (a) an extensive experience in open KT (n > 1100 KTs from 1991) and robotic urologic surgery (>4000 procedures from 2010, including radical prostatectomy, radical nephrectomy, partial nephrectomy, radical cystectomy, dismembered pyeloplasty, and ureteral reconstructive surgery); (b) a codified technique for RAKT; (c) a structured modular training in RAKT, including e-learning, simulation, and dry lab and wet lab training on animal models; (d) the availability of a multidisciplinary team (composed by urologists, anesthesiologists, nephrologists, radiologists, as well as operating room support staff and nurses) with experience in KT and robotic surgery; and (e) the opportunity to perform RAKT at nighttime and/or during the weekend in a dedicated operating room.

3.3 Selection criteria for RAKT from deceased donors

Following the University of Florence, recipient’s exclusion criteria for RAKT from deceased donors include the following: (a) age < 18 years; (b) severe comorbidities with contraindication for robotic surgery; (c) significant atherosclerotic plaques at the level of external iliac vessels; (d) highly complex vascular graft anatomy (likely to require multiple anastomoses); (e) multiple previous abdominal surgeries; and (f) previous KT. A key element of the RAKT program from deceased donor is also represented by the decision-making process aiming to assess the feasibility of RAKT in light of the patient-, graft-, and robotic team-related factors (Figure 9). As such, the decision to proceed with an “emergency” RAKT from a deceased donor relies on a careful balance of the potential advantages of robotic surgery (for both the patient and the surgeon) and the logistical challenges of setting up the operating room and the robotic surgical team in a fixed timeframe, respecting the recipient’s selection criteria and the maximal thresholds of cold ischemia time. Specifically, planning RAKT from deceased donors follows a pre-specified decision-making process. First, after the alert of a kidney offer is addressed to our transplant team by the Regional Allocation Centre, the surgeon in charge considers the opportunity to perform RAKT according to his/her personal experience and the availability of an expert bedside assistant as well as an expert robotic operating room nursing staff. Then, after the recipient is admitted to the nephrology unit for the pretransplant clinical work-up (which systematically includes a computed tomography angiogram of the abdomen to check for severe atherosclerotic plaques at the external iliac vessels), the surgeon checks that the recipient’s inclusion criteria are met. Subsequently, the robotic operating room is checked for availability (even during weekends, at nighttime, and potentially during daytime, if elective non-oncologic robotic procedures can be safely rescheduled), ensuring that the bench surgery starts within 16 hours from the beginning of cold storage of the kidney. Finally, at the time of bench surgery, the graft is carefully inspected to ensure no exclusion criteria for RAKT is present (i.e., highly complex vascular anatomy requiring multiple vascular anastomoses).

3.4 The University of Florence technique for RAKT from deceased donors

A step-by-step overview of our surgical technique for RAKT from deceased donors is shown in Figures 10–12.

All procedures were performed with the da Vinci Si® or Xi® robotic platform in a four-arm configuration with a zero-degree lens and one assistant port, by a single surgeon (G.V.) with extensive experience in robotic urologic surgery and open KT. The pneumoperitoneum pressure was set at 8 mm using the AirSeal® system, while the Trendelenburg was tilted at 20° in all cases.

The robotic instruments employed for RAKT included the following: (a) large needle driver; (b) black diamond micro-forceps; (c) monopolar curved scissors; (d) Maryland bipolar forceps; (e) prograsp forceps; and (f) robotic bulldog clamps. Laparoscopic instruments included a needle driver, the suction device, laparoscopic scissors, Hem-o-lok (Weck Surgical Instruments, Teleflex Medical, Durham, NC) clips and clip applier, Johan grasping forceps, and the drop-in ultrasound probe.

For insertion of the graft inside the abdominal cavity, we employ the GelPOINT® or the Alexis® wound retractor (Applied Medical, Rancho Santa Margarita, CA) through a Pfannenstiel incision (Figure 10). Regional hypothermia is achieved by cooling the graft with ice slush introduced through the GelPOINT® via modified Toomey syringes, as previously described.

Intraoperative indocyanine green (ICG) fluorescence videography (IFV) (i.e., FireFly® technology) is used to assess the graft and ureteral reperfusion.

Abdominal organ procurement is performed according to established principles for donors after brain death (DBD), while specific protocols were followed in the case of donors after circulatory death (DCD). In this setting, the kidneys are preserved in a hypothermic machine perfusion device (LifePort Kidney Transporter® (Organ Recovery Systems Inc. Chicago, USA)) before transplantation.

During bench surgery (Figure 10), the graft is perfused with Celsior® solution and inserted in a gauze jacket filled with ice (and closed with 4–5 stiches) after placement of a 6F, 14 cm double-J stent. Two landmark stiches are placed on the upper and lower sides of the graft vein, while one landmark stich is placed on the upper side of the graft artery, to facilitate the subsequent orientation of the graft inside the abdominal cavity. Finally, the graft artery is modeled to facilitate subsequent intracorporeal arterial anastomosis.

RAKT from deceased donors at our Institution follows the principles of the Vattikuti-Medanta technique, adopted by all other centers included in the ERUS-RAKT group.

Of note, this technique allows performance of a transperitoneal RAKT with final retroperitonealization of the graft after kidney reperfusion.

After induction of general anesthesia, port placement, and docking of the da Vinci Si/Xi robotic platform, the iliac vessels are dissected and prepared for subsequent anastomoses. Then, an extraperitoneal pouch is created, and access is gained into the Retzius space in order to prepare the bladder for subsequent ureteroneocystostomy.

Then, a Pfannenstiel incision is performed, and the GelPOINT® device or the Alexis® wound retractor is set in place. The graft is subsequently introduced into the abdominal cavity and the robot is redocked. After achievement of regional hypothermia, a venotomy is performed, the lumen of the external iliac vein is flushed with heparinized saline, and the venous anastomosis is completed in an end-to-side fashion using a 6/0 Gore-Tex suture on a CV-6 TTc-9 needle (Figure 11). After additional graft cooling, a liner arteriotomy is performed and converted into a circular arteriotomy with cold scissors. The renal artery is then anastomosed in an end-to-side fashion to the external iliac artery using a 5/0 Gore-Tex suture on a CV-6 TTc-9 needle with two running sutures (Figure 12).

After the integrity of the anastomoses is tested, the graft is revascularized and inspected for color and turgor. Intraoperative Doppler ultrasound with the TilePro® feature is employed to check for graft reperfusion in case the da Vinci Si robotic platform is used. On the contrary, if the da Vinci Xi® platform is available, graft and ureteral reperfusions are assessed using intraoperative indocyanine green (ICG) fluorescence videography (IFV). Then, the graft is allocated in the extraperitoneal pouch, which is partially closed by reapproximating the previously prepared peritoneal flaps with a V-lock running suture or single Hem-o-lok clips. This step avoids graft torsion, facilitates postoperative graft monitoring, and allows convenient access for ultrasound-guided transplant renal biopsy and/or placement of nephrostomy tubes, if needed. Interestingly, we recorded a laminar perirenal fluid collection in almost all patients at ultrasound examinations during the first postoperative period (i.e., postoperative days 1 and 7 and at hospital discharge). However, subsequent follow-up evaluations showed a progressive reduction of this fluid collection until complete reabsorption within 20–30 days after surgery, confirming the complete retroperitonealization of the graft.

The last step of the procedure is the ureterovesical anastomosis, which is performed according to a modified Lich-Gregoire technique over the double-J stent. The ureter is anastomosed to the bladder mucosa with two 4.0 Monocryl running sutures; then the detrusor muscle is closed creating an anti-reflux mechanism.

The technique for RAKT from deceased donors evolved over time throughout the learning curve. In particular, few technical nuances have been introduced, according to the surgeon’s preference and skills, with the aim to improve the esthetic result and the cost-effectiveness of RAKT, as well as to optimize critical steps such as the assessment of graft and ureteral reperfusion before ureterovesical anastomosis.

These technical modifications include insertion of the graft into the abdominal cavity through a Pfannenstiel incision (rather than a periumbilical incision), to improve the esthetic result of RAKT and facilitate the positioning of the graft in the pelvis close to the iliac vessels.

Second, the placement of the GelPOINT® device is achieved after preparation of iliac vessels, bladder, and extraperitoneal pouch, to make sure not to injure the bladder while positioning the GelPOINT® device through the Pfannenstiel incision. Of note, in the case of recipients with autosomal dominant polycystic kidney disease (ADPKD), all ports are positioned approximately 3 centimeters downward on the same lines to obtain an increased working space in the right iliac fossa far from the enlarged polycystic kidneys.

While mirroring the Vattikuti-Medanta technique, the steps of venous and arterial anastomoses differ slightly from those originally described by the ERUS-RAKT group. In all cases of right-sided grafts, an inferior vena cava (IVC) cuff is used during bench surgery to increase the length of the graft renal vein to facilitate the subsequent venous anastomosis. However, according to our experience in RAKT using right-sided grafts from living donors, the use of an IVC cuff does not appear to be mandatory, as the robotic platform facilitates the performance of a tension-free venous anastomosis even in case of short renal veins.

The venotomy is performed using the standard curved scissors (rather than the Potts scissors), and the venous anastomosis is completed in a two-step fashion: first, the posterior plate is closed using a running suture from 12 to 6 o’clock position; then, a knot is tied, and the anterior plate is completed with a second running suture with the same thread from 6 to 12 o’clock position (Figure 11). Tying the knot at 6 o’clock position after completion of the posterior plate may be key to reduce the tension on the anterior plate of the anastomosis, tailoring it according to the graft vein shape and length.

Similarly, the technique for arterial anastomosis follows the principles of the Vattikuti-Medanta technique with key technical nuances in case of deceased donors. First, the arteriotomy is achieved using standard cold scissors (rather than using the aortic punch). Second, due to the increased risk of atherosclerotic plaques and/or calcifications at the level of the external iliac arteries, the arterial anastomosis is performed using two different threads (Figure 12). First, the posterior plate of the anastomosis is closed using a running suture from 12 to 6 o’clock position, without tying a knot at 6 o’clock position. Then, the anterior plate is closed in a similar fashion with a running suture from 12 to 6 o’clock position using a second thread. Finally, the two free ends of the threads are tied together at 6 o’clock position, after checking the integrity of the anastomosis. This technique allows to tailor the tension of the anastomosis according to the stiffness and characteristics of both the renal and iliac vessels.

Third, the arterial anastomosis during RAKT from deceased donors is performed using a slightly thicker thread (Gore-Tex 5/0 instead of 6/0).

A specific challenge in case of RAKT from deceased donors is represented by the management of the Carrel’s patch for arterial anastomosis. At the beginning of our robotic program for deceased donor RAKT, after careful bench surgery showing no significant atherosclerotic plaques at the level of the renal artery ostium, we performed the anastomosis using the Carrel’s patch (Figure 12). However, with increasing experience the anastomosis is increasingly being performed without the Carrel’s patch. While in few cases at the beginning of the program, the surgeon had to remove the patch due to the presence of significant atherosclerotic plaques, in the following cases, the Carrel’s patch was removed intentionally during bench surgery, and the anastomosis was performed mirroring the technique adopted for living donor RAKT. From a technical point of view, and thanks to the robotic platform, removing the Carrel’s patch may provide significant advantages for the surgeon. These include (a) the opportunity to perform a shorter arteriotomy; (b) a more anatomic anastomosis, thanks to the similar caliber of the graft renal artery and external iliac artery; and (c) the reduced risk of atherosclerotic plaques at the level of the graft renal artery (as compared to Carrel’s aortic patch).

Finally, a specific technical modification proposed by our group for RAKT from deceased donors is represented by the use of intraoperative indocyanine green (ICG) fluorescence videography (IFV) to assess graft and ureteral reperfusion. The tips and tricks for the use of this technique during RAKT from deceased donors are discussed in the previous publications. In brief, a bolus of 0.3 mg/kg of ICG dissolved in 5% glucose (2 mg/ml) is administered intravenously after completion of vascular anastomoses to allow performance of a real-time qualitative and potentially quantitative assessment of graft and ureteral fluorescence signal. Forty seconds after ICG injection, the camera is switched to reveal fluorescence at the level of vascular anastomoses and the renal parenchyma and ureter to check for their reperfusion, allowing to adapt the ureteral length according to the fluorescence signal to reduce the chance of postoperative ureteral strictures.

3.5 RAKT from deceased donors: preliminary results

Overall, 32 RAKTs have been performed at the University of Florence from January 2017 (22.4% of all KT in this period).

The first RAKT from a deceased donor was performed in August 2017. Of the 32 RAKT performed so far, 19 (59.4%) were from deceased donors (n = 5 [26%] from DCD donors; n = 14 [74%] from DBD donors).

Interestingly, thanks to the structured RAKT program developed at the University of Florence, the proportion of RAKT increased over time in the last 3 years, being 18.3%, 26.4%, and 24% of all KT in 2017, 2018, and 2019, respectively. Similarly, the proportion of RAKT from deceased donors increased over time, being 11.1% in 2017, 19.6% in 2018, and 14.3% in 2019 of all KT from deceased donors.

The University of Florence group very recently published their results on their first 17 RAKTs from deceased donors. They now performed 19 cases, all successfully completed without need of open conversion.

The da Vinci Si and Xi robotic platform was used in 15 (79%) and 4 (21%) cases, respectively. In the vast majority of cases (n = 17), RAKT was performed in the right iliac fossa.

The graft was introduced using the GelPOINT® device (or the Alexis® port) in 14 (73.7%) cases through a Pfannenstiel incision, while in 5 (26.3%) through a periumbilical incision.

They recorded one case of intraoperative complication (intraoperative bleeding not requiring transfusion) that required positioning of an additional 5 mm port to increase exposure and help aspiration. Three patients (16%) suffered a high-grade (Clavien-Dindo grade 3) complication (transplant renal artery stenosis requiring percutaneous angioplasty in one patient; percutaneous placement of a nephrostomy tube for hydronephrosis in one patient and transplant renal artery thrombosis requiring graft nephrectomy).

A progressive improvement of renal function was recorded at all time points during the postoperative period. Median eGFR at hospital discharge (median 12 days post-op) was 47.2 ml/min/1.73m² (IQR 28.9–59.4), while median eGFR at a median follow-up of 15 months was 58.6 ml/min/1.73m² (IQR 40.0–80.4).

Overall, five (26%) patients required dialysis during the first postoperative week. Of these, one patient due to primary nonfunction after RAKT from an uncontrolled DCD donor; one patient due to graft nephrectomy due to arterial thrombosis; one patient for suspected acute rejection treated with intravenous corticosteroids; and two patients for DGF.

At a median follow-up of 15 months, all patients are alive, and two patients are still on dialysis.

3.6 RAKT from deceased donors: future perspectives

We developed the first structured program of RAKT from deceased donors worldwide.

Despite being preliminary, our experience confirms the feasibility of RAKT in this donation setting in centers with a solid background in open KT and robotic surgery and after proper standardized modular training.

From a logistical perspective, RAKT from deceased donors poses specific challenges, which require a comprehensive, multidisciplinary effort to redesign the management strategy of the institution’s transplantation pathway. In this view, a highly trained and committed surgical team, as well as the opportunity of a dedicated flexible robotic operating room, are key elements for the success of the program.

The perioperative and functional data in our preliminary series are promising but warrant further investigation. In particular, larger studies with longer follow-up are needed to confirm the safety of RAKT from deceased donors (especially DCD donors), to evaluate the impact of learning curve on patient outcomes, and to identify the predictors of adverse perioperative events (i.e., major surgical complications, PNF and DGF) to refine patient selection.

Yet, extending the number of robotic transplantations performed by centers experienced in robotic surgery using grafts from deceased donors would be key to increase the pool of patients who may benefit from minimally invasive surgery. Notably, this is a critical step toward the definition of evidence-based indications for RAKT in this clinical scenario also from a Guideline’s perspective.

We entirely share Dr. Alcaraz and colleagues’ perspective that “although major improvements in outcomes for transplant patients are likely to come from the field of immunology, small, measurable improvements may yet be possible via technical advances”. As such, we believe RAKT, which is likely to be increasingly performed by referral transplant centers worldwide, may provide unique opportunities for both patients and surgeons, allowing to improve the precision and reduce the morbidity of this procedure. To move the field forward, implementing RAKT programs from deceased donors is the most compelling clinical unmet need for the transplant and urological community.

4.1 History and background

In 1902 Ullmann and Carrel experimentally achieved the first successful animal kidney autotransplantation (KAT), moving the kidney of a dog from its lumbar fossa to its neck, in this way laying the foundations for future kidney (auto)transplantation. In 1956, the Brazilian Campos Freire attempted KAT for the first time on a man with a renal artery aneurysm, although an early thrombosis forced him to perform a nephrectomy. In 1961, Shackman and Dempster repeated this in a case of unilateral renal artery stenosis but with unsatisfactory results. It was not until 1963 when JD Hardy et al. achieved the first successful KAT in human in a case of high ureteral stricture after a large aortic aneurysm repair. McLaughlin et al. demonstrated its utility in the management of complex renal lesions. Following these pioneering surgeries, KAT was adopted as a method to perform renal artery angioplasty in treating hypertension caused by severe renal artery stenoses. In these vascular cases, the ureter was usually not transected; the vascular pedicle is reconstructed in or close to the abdominal incision with subsequent vascular reimplantation on the iliac vessels, making this actually a renal transposition. Only when the indication concerns primary ureteral pathology or when the kidney needs complex surgery on the bench table (and both the vascular pedicle and the ureter are sectioned and subsequently reimplanted), the term KAT is correct. Nowadays, most renovascular problems are treated with endovascular methods, and the indications for KAT have been shifted more toward managing complex ureteral strictures or malignant pathologies for which endoluminal or in vivo repair is impossible or contraindicated. Less frequent indications include loin pain hematuria syndrome, retroperitoneal fibrosis, and metabolic stone disease.

KAT is an important surgical last resort technique in order to spare the kidney in select cases. It allows ex vivo management of complex renal or ureteral pathology, which would not be treatable with conventional techniques, without resulting in important kidney function loss. For this purpose, the harvested kidney is cooled on ice slush and flushed with an ice-cold preservation solution during bench surgery, thus reducing tissue oxygen requirement.

Traditionally, KAT has been performed through a large midline laparotomy, a large paramedian extraperitoneal incision or the combination of a lumbotomy for the nephrectomy phase with a lower abdominal incision for the transplantation phase; thus being a very invasive procedure, and, albeit having a low mortality rate (1.3%), postoperative morbidity may be as high as 46.2%. Due to the historic invasiveness of the procedure, and the unfamiliarity of many urologists with the field of KT, KAT has never gained much popularity and often these kidneys were sacrificed. However, since the introduction of laparoscopy in urology, attempts have been made to reduce the morbidity of open KAT. Fabrizio et al. described in 2000 the first laparoscopic nephrectomy for KAT; however, the patient still required a periumbilical incision for extraction of the graft and a pelvic incision for the transplantation. Today, the most accepted approach is to perform laparoscopic nephrectomy, via a three-port transperitoneal access, and open KAT, using the classical Gibson incision for both extraction and introduction of the graft, resulting in possible low complication rate and excellent long-term autograft function.

In recent years, due to the success of RAKT, interest is rising to reevaluate KAT as an ultimate nephron-sparing option in complex cases. In 2014, Gordon et al. published the first case of robot-assisted kidney autotransplantation (RAKAT) to treat extensive ureteral loss after complicated ureterorenoscopy for ureterolithiasis. They used a completely intracorporeal technique, establishing in vivo hypothermic renal perfusion by continuous renal artery irrigation. The robot was redocked between nephrectomy and transplantation phase, and the table was repositioned rather than the patient. The complete intracorporeal technique was successfully repeated by Lee et al. in 2015. Despite these promising results, the totally intracorporeal technique is not suitable in patients where ex vivo bench repair is required (e.g., multiple vessel grafts, complex oncological cases, lithiasis treatment) or where the surgeon would prefer to transplant the autograft in the contralateral iliac fossa (e.g., disturbed pelvic vascular anatomy or excessive fibrosis). In the same period, Sood et al. theoretically described a technique for RAKAT using extracorporeal tabletop graft reconstruction, using a GelPOINT device, in order to broaden indications of RAKAT. In 2017, Araki et al. published a case using this extracorporeal RAKAT technique in a patient with proximal ureteral stenosis. Also in 2017, Decaestecker et al. performed the first extracorporeal RAKAT in Europe and to date have the largest series of RAKAT worldwide. This European series also adopted a totally intracorporeal technique.

4.2 Operative technique

Decaestecker et al. published the largest series of RAKAT worldwide, all for non-oncological cases. Their technique is based on the experience within the ERUS-RAKT working group, as described by Breda et al., and on the theoretical report by Sood et al. We will describe the extracorporeal bench work technique and the totally intracorporeal technique with the da Vinci Si® and Xi® robotic platform.

Nephrectomy for living kidney donation has been performed laparoscopically for more than two decades. Minimally invasive surgical techniques have substantially contributed to the future development of transplant programs and among others significantly increased the number of potential living donors. This evolution was fueled by the fact that minimally invasive operative techniques generate significant patients’ benefits such as reduction in postoperative pain, decreased length of hospital stay, better cosmetic results and lower morbidity rates.

In this context, robotic assisted nephrectomy for living kidney donation has become a well-established procedure, competing for supremacy with laparoscopic and hand assisted minimally invasive approaches. Unlike in other surgical interventions, living kidney donation involves healthy altruistic individuals, who are willing to undergo major surgery for the wellbeing of another human being. Minimization of any potential risk factors thus maximizing donor safety is even more highest priority.

Hemorrhagic complications resulting from inadequate renal artery closure in living kidney donation surgery have been shown to jeopardize donor life and health. Opinions about the safety of specific techniques of renal vascular closure are heterogeneous and predominantly investigated in open and laparoscopic procedures of living kidney donation. In general, transfixing techniques using various vascular stapling devices and surgical sutures are considered superior when compared with non-transfixing techniques like clips and ligatures. A survey among surgeon-members of the American Society of Transplant Surgeons (ASTS) however, also revealed that multiple locking clips are still commonly used in laparoscopic cases of living kidney donation.

From a technical perspective robotic assisted surgery provides the surgeon with enhanced 3D visualization of the operative field and the use of wristed instrumentation allows tremor free articulation with seven degrees of freedom. Surgeons intraoperative comfort while using the robotic unit has been described to be extremely high, resulting in continuous steep reproducibility rates of various major surgical interventions.

The first series of robotic assisted laparoscopic donor nephrectomies were reported in 2001. Recent data suggest that robot assisted nephrectomies account for a fraction of 3,8% of all minimally invasive donor nephrectomies, numbers increasing. Published data suggest that renal vascular closure in robotic assisted nephrectomy for living donation (RANLD) has been prevalently performed safely with vascular staplers.

The da Vinci Surgical System^® (Intuitive Surgical, Sunnyvale, CA) is currently the most used device with more than 3,500 operating platforms worldwide. As the company’s name suggests, the design and handling of the robot is meant to be intuitive for a first-time user, which allows for a steep learning curve for novices.

Here we describe the experience of our first 40 consecutive robotic assisted donor nephrectomies with regard to pre- and intraoperative strategies and postoperative outcome. In contrast to previous studies we used multiple locking clips or a combination of clips and suture ligatures for renal vascular closure.

Methods

Results

From November 2013 till August 2018, forty consecutive RANLD were performed at our center. Within this time period an exponential increase of donation surgeries could be detected (Figure 1). A number of 13 cases alone was performed within the last 8 months, which represents 32.5% of the total patient volume. Sex distribution among donors was n=21 (52.5%) women and n=19 (47.5%) men, with a donor’s average age of 53.075±11.68 years (range, 28–70) and an average body mass index of 25.99±3.58 kg/m² (range, 19.9–35.3 kg/m²). All donors were Caucasian. Relation to the recipient was distributed in parent (n=18, 45%), sibling (n=5, 12.5%), spouse (n=9, 22.5%) and children (n=1, 2.5%) for direct relation as well as other (n=7, 17.5%) for a very close relationship. Preoperative laboratory parameters showed average creatinine values of 72.7±11.95 µmol/L and a mean glomerular filtration rate of 92.48±12.46 mL/min/1.73 m² (see all Table 2).

A total of n=21 (52.5%) left and n=19 (47.5%) right kidneys were used for donation. Hereof n=31 (77.5%) kidneys had a single arterial vascular supply and n=9 (22.5%) a multiple (seven donors with 2 arteries and two with 3 arteries). Venous vascular supply was as follows: n=37 (92.5%) single and n=3 (7.5%) multiple (maximum of two veins) (see all Table 3). Eighteen cases, (including all cases with multiple vessel supply) were operated with double clipping of renal vessels using locking hemlock clips and in 22 cases vessels were addressed with one locking hemlock clip and one Vicryl ligature (Vicryl 3-0). No significant difference in warm ischemia time (WIT; defined as time from renal artery closure to cold perfusion) was evident in both groups (WIT double clipping: 3.9±1.2 min vs. clip + ligature: 3.8±1.5 min, P=n.s.).

Overall mean operative time was 150.75±27.30 min with no individual difference between the two surgeon specialists (surgeon A with n=18 RANLD and a mean operation time of 153.11±30.92 min, surgeon B with n=22 RANLD with a mean operative time of 148.8±24.53 min, P=0.636). Also, the mean operative time for patients with single 150.9±26.99 min or multiple 150.27±28.99 min vascular supply (arterial and or venous) showed no significant difference (P=0.949) (no figure provided).

Interestingly a significant difference in operation time could be detected when looking at the donation side. Right donor nephrectomy (139±22 min) was performed significantly faster than left (160.95±27.93 min) (P=0.01) (Figure 2).

Total operation time gradually decrease with the numbers of robotic donor nephrectomies performed (Figure 3). There was also a significant decrease in operation time when comparing the first 20 RANLD (161±29.16 min) with the last 20 cases (140.5±21.38 min) (P=0.016).

Average warm ischemia time (WIT) was 2.25±0.63 min. 30 patients received an intraoperative drainage (Redon, 16 Charr), placed in the nephrectomy loge. First eight Patients were transferred to the ICU postoperatively for safety reasons. The mean length of stay was 1.25±0.54 days (range, 0–2). Average length of hospital stay was 7.25±3.59 days (range, 4–21). Mean value of postoperative serum creatinine at day of discharge was 114.05±18.42 µmol/L and average GFR was 55.89±11.17 mL/min/1.73 m².

No conversion to hand assisted, laparoscopic or total open surgery was necessary. There were no intraoperative complications. A number of five (12.5%) postoperative complications were identified. Clavien-Dindo grade I complications occurred in n=2 (5%), lymphatic fistula, urinary tract infection), grade IIIa complications occurred in n=1 (2.5%) (abscess of the trocar insertion site) and grad IIIb complications occurred in n=2 (5%) n=1 fascial dehiscence and n=1incisional hernia). Grad IV and V complications did not occur (see all Table 4).

Similar to results of operative time, there is a small difference for complication rate between the first 20 (n=3, 7.5%) and the second 20 (n=2, 5%) cases. Donor mortality was 0%. Thirteen kidneys (32.5%) were transplanted across the AB0 barrier, requiring therapeutic apheresis as well as T and B cell directed immunosuppressive therapy for the recipient.

Discussion

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. In particular, live kidney donation has been shown to be superior to deceased donor kidney transplantation mainly in terms of long-term benefits and better graft survival. In Germany, living donor kidney transplantation is currently available in 37 transplant centers, and 39% of all kidney transplants in 2018 were living donor related.

As surgical robots begin to diversify into all different fields of surgery worldwide, innovations in robotic surgical procedures continuously strive to improve patients’ outcome, including the field of transplant surgery.

Our data support the evidence of a limited number of articles highlighting the feasibility and safety of robotic assisted living kidney donation. The majority of European, American and Asian transplant centers performing living donor kidney transplantation offer their patients a minimally invasive donor organ procurement strategy. The elective type surgery allows transplantation of kidney grafts with excellent function to recipients under optimal conditions. Living kidney donation furthermore allows to reduce wait time to transplantation and time on dialysis and should therefore additionally be propagated in the field of transplant surgery. As described earlier, older age and comorbidities such as moderate hypertension and a BMI >30 kg/m² are no contraindications at our center and have again proven safe outcomes for the donor.

Interestingly the introduction of robotic assisted donor surgery has furthermore propelled the living kidney donation program in our center. A similar effect has already been described by Oberholzer et al. for the kidney transplantation program at the University of Illinois at Chicago. In 2001 for the first time the number of living kidney donors has exceeded the number of transplantations with organs from deceased donors in several specialized transplant centers. In 2018 almost 39% (n=638) of all kidneys transplanted (n=1,653) in Germany were living donor related. This mirrors our numbers of living donations which have almost quintupled within the last 5 years since our debut of robotic assisted donor surgery.

Renal scintigraphy and volumetry for split renal function assessment are key decision parameters for donor side selection, which generally falls for the side with inferior function. Accurate preoperative evaluation of renal vascular anatomy using CT angiography or MRI imaging is vital for successful and safe postoperative outcomes. As a principle we selected the kidney with inferior function and smaller number of vessels. If split renal function was well balanced, we generally selected the left kidney for anatomical reasons which are mainly the longer renal vein. We share the idea that in contrast to early publications, kidney grafts with multiple vessels are no longer considered as a relative contraindication for living donation. In this context our cohort included an amount of 27.5% donor organs with multiple (n=2 or n=3) renal arteries, all originating from the aorta. In case of a significant difference of split renal function (more than 5% difference) we did not hesitate to select the qualitatively inferior kidney for donation, even if the number of vessels was increased.

Although uncommon, major vascular complications during minimally invasive donor nephrectomy can be potentially fatal. Based on data from laparoscopic donor nephrectomies, it has been postulated that vascular clips alone are inadequate for safe closure of the main renal artery and vascular staplers would be saver due to transfixion of the vessel wall. In 2006 the US Food and Drug administration (FDA) and the manufacturer of the hemlock clip, Teleflex, as a reaction to two death of living kidney donors, announced a recall stating that the use of hemlock clips in laparoscopic donor nephrectomy is contraindicated. In addition, three live kidney donors, two form the United States and one from India reportedly died after the release of the statement and several other donors obviously suffered severe hemorrhagic events from clipping failures during laparoscopic kidney donation. This is a substantial dilemma, and we strongly believe that the incidence of fatal vascular complications in living kidney donation is even under-reported. By now, from all vessel sealing devices and techniques that were used for laparoscopic kidney donation [intracorporal knot tying, bipolar vascular sealing devices ultrasonic shears staplers and clips still remain the prevalent techniques used for vascular control. The reason why staplers may not have entirely replaced clips in this surgical scenario may be the fact that stapler use is itself is associated with a considerable amount of malfunction. In addition to malfunction stapler use in laparoscopic kidney donation is furthermore associated with donor vessel length shortening and increased operative costs.

In our patients, we either used two locking hemlock clips, or a combination of one locking hemlock clip and one Vicryl 3-0 ligature for renal artery closure. Informed consent on this technique was obtained by all patients. Our strategy is supported by a recent metanalysis on vessel controlling devices for renal pedicle ligation in laparoscopic live donor nephrectomy, which revealed no significant differences between hemlock clips and staplers with regard to device failure rate, death rate and severe hemorrhage rate. Our strategy utilizes the full capacity of the robot, namely enhanced 3-D vision and when indicated, the ability of delicate intracorporal tying. This method does not waste significant millimeters of vessel length when compared to vascular stapling and seems to be cost effective. When compared to the robotic clip applicator, the conventional re-usable laparoscopic applicator proved sufficient, allowing for even more cost savings in our setup.

Furthermore, the simultaneous use of two laparoscopic clip applicators, one used for clipping and another one ready to be applied might furthermore reduce warm ischemia time, since the repeat loading of one robotic clip applicator might be more time consuming.

In case of multiple vascular supply, the individual vessel diameter trends to be smaller. Under these circumstances our strategy of double clipping proved to be save. Our indigenous technique furthermore does not significantly delay the operation time or increase warm ischemia time. We believe that vessel length might be of crucial importance in case of multiple artery supply, requiring microvascular reconstruction before transplantation. Reduction of material costs in terms of saving expenses for stapling devices, might in our situation furthermore compensate for the current global higher costs associated with robotic surgery.

In general, robotic operations are predominantly performed by two surgeons, one handling the robotic console and the second one scrubbed in the operating field for assistance. In contrast, fully laparoscopic, laparoscopic hand assisted, or open donor nephrectomies may require up to three surgeons depending on the strategy and technique.

In comparison to previous studies our mean operative time was relatively low. This is probably due to the fact, that both surgeons have a work experience with the robotic platform of more than 10 years, having completed more than 400 complex robotic assisted kidney surgeries each. Still a learning curve was evident after the first 10 operations for each surgeon, resulting in a decrease of operation time and patient morbidity. In parallel, steep learning curves have also been reported for both minimally invasive retroperitoneoscopic and laparoscopic donor nephrectomies. 3-D vision which is not only exclusively restricted to robotic assisted operations, but also broadly available for laparoscopic procedures in general seem to reduce operation time and warm ischemia times when compared to 2-D techniques.

Interestingly multiple vessel supply did not have a significant impact on operation time or warm ischemia time, nor did it have an impact on graft survival or morbidity after transplantation (data not shown). This supports our strategy of vessel occlusion, using a combination of both ligatures and clips.

A new surgical technique must always be compared to the gold standard. RALDN has been reported to be feasible and save, although operation time and warm ischemia time in some studies may be slightly longer when compared to laparoscopic kidney donation. A recent study however, revealed that skin to skin time of RALDN approached that of laparoscopic which each subsequent procedure, and the standard operation time of the laparoscopic kidney donation procedure could be reached at the 22^nd case. Longer operation times might hypothetically be explained with an initial cautious and slower approach of the surgeon to an unfamiliarly procedure.

Our study presented here is not devoid of limitations, which are mainly a small sample size and the retrospective character, which has to be taken into consideration. We used a total of six trocars for the robotic procedure which is two more than in the average laparoscopic procedure. In addition to the 4 robotic trocars (three working trocars and one camera trocar) our additional two trocars are necessary for simultaneous suction irrigation and clip application. Admittedly we also have a fairly high complication rate, especially when it comes to fascia dehiscence and early hernia development. This might be directly related to the Rutherford Morrison incision, since no complications developed when a Pfannenstiel incision was used for kidney extraction.

However, to date no data using explicitly hemlock clips or ligatures for renal vascular control in robotic assisted living kidney donation have been published. Further prospectively randomized studies involving robotic surgery in living kidney donation are in demand.

We consider the robotic assisted nephrectomy for living kidney donation as the method of choice for the experienced robotic surgeon which incorporates lowest donor risks and highest reproducibility rates. Vascular closure with two locking clips or a combination of one locking clip and one ligature have been proven save and feasible using the robotic platform. Laparoscopic or hand-assisted laparoscopic techniques may always be taken into consideration for selected cases or at institutions where a robotic device is currently not available.