Simultaneous Living Donor Kidney Transplant and Laparoscopic Native Nephrectomy: An Approach to Kidney Transplant Candidates with Suspected Renal-Cell Carcinoma

Introduction

The discovery of an existing cancer in a patient under consideration for a kidney transplant presents an important dilemma. Based on population studies, patients with end-stage renal disease (ESRD) are at increased risk of certain cancers. ^1,2 In particular, previous studies have shown a high incidence of renal-cell carcinoma (RCC) in patients with ESRD, with a standardized incidence ratio of 3.6. ³ Similarly, a surveillance program of transplant candidates using ultrasonography reported an increased RCC incidence of 2.7%. ⁴ Aside from screening programs, patients undergo an extensive work-up to determine their candidacy for renal transplantation. ⁵ This work-up often includes imaging, which can reveal incidental findings such as concerns for malignancy that must be addressed. Malignancy, prior or newly discovered, is one of the most common reasons for delay in transplantation.

In most circumstances, cancer treatment with a tumor-free waiting period before proceeding with transplantation is necessary because the risk of mortality from cancer may preclude the patient from realizing the long-term benefit of the transplant. Additionally, the immunosuppression required for the transplant may predispose to a worse oncologic outcome. One established exception, however, is the scenario of a patient with hepatocellular carcinoma undergoing a liver transplant, which has been practiced for more than 20 years, with good outcomes. ⁶ However, a key factor in that situation is that the native liver, including the cancer, is removed in the process of the transplant. In contrast, the native kidneys are not routinely removed in the process of a kidney transplant. Thus, a patient with an existing RCC who is being considered for a kidney transplant poses a particular challenge.

Patients on the deceased donor transplant waiting list that are found to have a suspicious lesion in a native kidney typically undergo treatment of that lesion before being considered an acceptable candidate for transplantation. Given the organ shortage and the resultant long waiting times to receive a deceased donor kidney transplant, it is reasonable to first address any lesions before considering transplant. However, the scenario of a patient under consideration for a kidney transplant from a living donor, who is found to have a concerning lesion in a native kidney, represents a situation for which there is little published experience. While a common approach may be to treat the lesion before pursuing transplant, this can result in a delay of several months, possibly adding logistic barriers to transplant. This is a particular risk if a paired kidney exchange is involved, with multiple donors and recipients contingent on specific timing and pairing. ⁷ Additionally, there are potential benefits, including efficiency of undergoing simultaneous native nephrectomy and transplantation. At our institution, patients with a readily available living donor who were incidentally found to have a suspicious lesion in a native kidney have been considered for simultaneous transplantation and laparoscopic native nephrectomy. In this study, we report our experience with this approach and the long-term follow-up of these patients, to aid other clinicians who are faced with a living donor transplant candidate with a concerning renal mass.

Methods

This is a retrospective review of all patients who underwent simultaneous living donor kidney transplant and laparoscopic native nephrectomy at our institution between 2013 and 2018. We focused on this recent period in which there has been broader use at our institution of laparoscopic nephrectomy in the context of transplant surgery. Data were obtained from a prospectively maintained comprehensive database of kidney transplant recipients at our institution. Patients who underwent a living donor kidney transplant and simultaneous native nephrectomy for the indication of a suspicious lesion were included. One patient who underwent a deceased donor kidney transplant and simultaneous native nephrectomy was not included in the analysis, given the rarity of this situation, and the unique considerations involved with a deceased donor. Before the chosen study period, there were cases of a simultaneous native nephrectomy performed through an open approach and for non-oncologic indications. These patients were excluded from analysis, as well as patients who underwent bilateral native nephrectomies for polycystic kidney disease.

No preoperative biopsies were performed based on the small size (<4 cm) and radiologic features of the masses. In all cases, the imaging was suggestive of a possible RCC. If there were concerns for a tumor of urothelial origin, simultaneous nephrectomy was not offered to the patient. Instead a nephroureterectomy would be performed, followed by a waiting time of at least 2 years before transplant. All patients had at least 1 year of post-transplant follow-up. Patients found to have RCC on nephrectomy pathology underwent routine RCC surveillance post-transplant with annual CT scans and chest X-rays. Baseline patient characteristics, indications for transplant and native nephrectomy, surgical details, and pathology were analyzed. This study met Weill Cornell Institutional Review Board approval.

Preoperative consent included discussion of alternative treatments of the suspicious masses, including surveillance or radiofrequency ablation, as well as the particular risks relating to the simultaneous approach, including the risk of cancer progression. All donors at our institution are generally informed as part of the evaluation process about the risk of failure of their donated kidney, but in the interest of preserving the recipient's privacy, no specific details relating to the possible RCC were routinely provided to the donor. Similarly, all donors are told that there is a rare possibility of canceling the transplant, even after the donor may have been anesthetized, in the rare situation that the recipient becomes unstable or unsuitable to proceed with the transplant. Nevertheless, in most cases, the donors were aware of the recipient's unique scenario and had been directly informed by the recipient, or the recipient had given us permission to disclose such information to the donor. In logistic planning of the donor and recipient operating rooms, the donor and recipient procedures were each performed in separate and adjacent operating rooms, concurrently. To minimize cold ischemia time, the donor kidney was generally not removed until the recipient was ready.

Native nephrectomy was performed by variations of a laparoscopic approach, whether through multiple ports or a single port, and with or without a hand-assist. These approaches have been described previously. ⁸ Given the concerning renal masses, a radical nephrectomy was performed. Two different surgeons were involved, one who performed the laparoscopic native nephrectomy and the other who performed the open transplant. In all cases, the native nephrectomy was performed first and the transplant followed immediately after. Nephrectomy specimens were routinely sent for permanent fixation, without obtaining a frozen-section, unless there was an intraoperative concern. With the laparoscopic nephrectomy approach, the kidney was placed in an Endo Catch bag and then retrieved via the subsequent transplant incision, regardless of the laterality for each procedure. For example, even if the native nephrectomy was on the left side, the specimen could still be removed, and the transplant performed, through either a right-sided or a left-sided Gibson incision, depending on the various relevant considerations. The peritoneal defect was not closed.

The postoperative course involved general recovery and administration of induction immunosuppression. The choice of induction agent and the use of maintenance steroids were based on standard institutional protocol, irrespective of the possibility of RCC in the native kidney. Our general protocol includes antithymocyte globulin as induction (total of 6 mg/kg) and maintenance with tacrolimus and mycophenolate mofetil, typically steroid-free. ⁹ Patients are usually discharged on postoperative day 4.

Results

There were 16 patients who met the inclusion criteria, having undergone a simultaneous living donor kidney transplantation and laparoscopic native nephrectomy for a suspicious lesion. A summary of the cases is shown in Table 1. In this same period, there were a total of 1533 transplants from living donors (60.4%), and 1007 from deceased donors (39.6%) performed at our institution. All the study cases involved a unilateral native nephrectomy, with the exception of one case of bilateral native nephrectomy for suspicious lesions in each of the native kidneys. In all cases, the lesions were identified preoperatively. Of the 16 patients, RCC was found in the nephrectomy pathology specimen in 10 (62.5%) cases, and the remaining patients had benign renal lesions. A summary of the pathologic findings is shown in Table 2. Two patients were found to have two separate renal tumors within a single kidney. In all cases, the margins were negative, and there were no positive lymph nodes.

The average age at the time of transplant was 58.1 years (range: 41.4–73.9 years). Twelve (75%) patients were on hemodialysis preoperatively, and four (25%) patients were not on dialysis at the time of transplant. On average, the recipient went into the operating room 48 minutes before the donor (range: 17 minutes before to 123 minutes after). On average, the recipient's surgical incision time was 30 minutes before the donor's (range: 47 minutes before to 94 minutes after). The average operative time for the donor nephrectomy was 133 minutes (range: 89–177 minutes). The mean total operative time for the combination of the recipient native nephrectomy and transplant was 268 minutes. The average cold ischemic time, defined as the time from the stapling of the first renal artery, until reperfusion, was 67.6 minutes (range: 36–121 minutes). The mean combined estimated blood loss was 138 mL, with a range of 50 to 400 mL, and none of the patients required an intraoperative blood transfusion.

For induction immunosuppression, 13 (81.3%) patients received antithymocyte globulin and 3 (18.8%) patients received basiliximab. Basiliximab was chosen for two patients due to being two-haplotype matches, and for one patient who was deemed high cardiac risk. The median hospital length of stay was 4 days, with a range of 3 to 22 days. There was only one complication that was grade 3 or above, using the Clavien classification: a urine leak, which required operative repair—this was unrelated to having had a simultaneous native nephrectomy. ¹⁰ There were no cases of delayed graft function, as defined by the requirement for dialysis within the first week after transplant.

The average creatinine was 1.83 mg/dL at 12 months, 1.98 mg/dL at 24 months, and 2.09 mg/dL at the date of last follow-up. The average follow-up was 3.96 years, ranging from 1.55 to 6.22 years. There were three cases of biopsy-proven acute rejection (18.8%) at the time of last follow-up, including two cases of acute cellular rejection and one case of antibody-mediated rejection. There was one graft failure due to rejection at 1.6 years post-transplant. At a mean of nearly 4 years of follow-up, there were no cases of recurrent RCC, and all patients were alive, including the one with a failed allograft.

Discussion

Historically, patients with an active malignancy were not eligible for transplantation, due to the concern that the immunosuppression required for the transplant may worsen cancer outcomes. Furthermore, the risk vs benefit of a transplant may not be favorable if there is a significant risk of mortality from the malignancy. However, while conceptually straightforward, there are certain questions that arise. For instance, how extensively should transplant candidates be evaluated to ensure that there are no active malignancies? ¹¹ Additionally, for those with cancer, how much time must elapse before pursuing transplantation? ¹² For small (<5 cm) or incidentally discovered RCC, there is some consensus that no specific waiting time is required after cancer treatment. The American Society of Transplantation has published practice guidelines recommending 2 years waiting time after removal of symptomatic RCC, and 5 years after large (>5 cm) and/or invasive RCC. ¹³ While these recommendations provide guidance on a tumor-free waiting period before transplantation, they are based on the assumption that the patient has undergone cancer treatment. In this study, for patients with a suitable living donor and an incidentally discovered possible RCC, we have chosen to proceed with simultaneous transplant and cancer operation. To the best of our knowledge, this series represents the largest published experience of this approach.

An alternative approach would be to perform the transplant and postpone the nephrectomy until a later time, based on the experience of transplant recipients who develop a suspicious mass in a native kidney post-transplant. ¹⁴ In fact, Suson and colleagues have published their experience of 15 such patients with good outcomes. ¹⁵ In that case, close monitoring would be critical, as Ryosaka and colleagues have shown rapid progression of RCC in some transplant recipients. ¹⁶ A potential benefit of a simultaneous rather than a staged approach is subjecting a patient to only one operative experience. Incisions can be planned to minimize their number, without introducing the risk of entering a reoperative field. Another potential benefit is for patients undergoing preemptive living donor transplant, in which a simultaneous approach allows the recipient to avoid the possibility of having to initiate dialysis after nephrectomy without simultaneous transplant. However, a potential risk with a simultaneous operative approach is that the risks of each individual procedure can be compounded. For example, a significant intraoperative complication at the time of the nephrectomy could jeopardize the outcome of the transplant. This issue could be further magnified in the event of a paired kidney exchange, in which multiple transplant pairs are contingent on each other, and so, an unexpected intraoperative finding that causes the transplant to not proceed could then break an entire chain of transplants. In the event of a major intraoperative complication, during the nephrectomy or at any point before the transplant, a decision would need to be made regarding the role of aborting the transplant. In addition, there is risk in not knowing the results of the final pathology before proceeding with transplant, as the histologic findings could affect the management and appropriateness of proceeding with transplant.

Besides nephrectomy, an alternative treatment approach for patients with small, incidentally detected RCC is radiofrequency ablation or cryoablation. ^17,18 Ablation may be considered for selected patients with masses <4 cm who are poor surgical candidates or who require nephron-sparing treatment of their masses. While ablation was discussed preoperatively with our patients, the decision was made to proceed with resection as both diagnosis and treatment of the lesion, while minimizing the need for long-term surveillance, and given the limited role for preserving native renal function in the setting of ESRD.

There are several technical and logistic considerations worth noting about the simultaneous approach. In all cases, the peritoneal defect created for native kidney extraction was not closed. However, the peritoneal defect could have been closed to preserve a retroperitoneal location of the allograft. Also, we conventionally place the allograft on the patient's right side, barring other considerations such as a prior transplant or significant vascular disease. However, there may be a benefit to placing the allograft on the contralateral side of the native nephrectomy, to ensure the availability of the native ureter in the event of any transplant-ureteral complications. A simultaneous nephrectomy and transplant approach requires logistic coordination, in particular with operating room facilities and staff. In fact, some of these transplants were performed on a day when there was a second pair of living donor and recipient at our institution. We recognize that to accommodate some of the scenarios, such as having three or even four simultaneous operating rooms, may be impossible or impractical in different practice settings.

In this series, there were no major complications related to the combination of both procedures. There were no significant unexpected findings intraoperatively, and all transplants proceeded as planned. All patients were maintained on our standard immunosuppression medications, although mechanistic target of rapamycin inhibitors may be considered, given their efficacy against RCC. ¹⁹ At nearly 4 years of overall follow-up, no patients had recurrent RCC. This time frame is particularly important as the greatest risk of recurrence for RCC occurs within the first 5 years after nephrectomy, with the majority of recurrences occurring within 3 years. ²⁰

Based on these results, we believe that simultaneous living donor kidney transplant and laparoscopic native nephrectomy represents an acceptable approach in select patients with small (<4 cm, T1a) suspicious masses who are otherwise at low risk for intraoperative complications. Our practice is to perform the donor nephrectomy in one room, while a second team performs the recipient nephrectomy in another room simultaneously. Ideally, both the donor and recipient nephrectomies are completed simultaneously, so the kidney transplant may proceed with minimal ischemic time. However, this approach requires logistic coordination, facilities, and staffing that may not be available at all transplant centers. Given the organ shortage, and the importance of living donor transplants, this approach supports the maximization of opportunities for living donor kidney transplants.