Perioperative Outcomes of Laparoscopic Radical Nephrectomy for Renal Mass in Patients on Dialysis or with Renal Transplant in Place Compared to Normal Controls

Abstract

Background:

The risk of renal cell carcinoma (RCC) development in the native kidney of patients on dialysis or with a renal transplant is increased compared to the general population. This study examines perioperative outcomes of laparoscopic radical nephrectomy (LN) in dialysis patients or renal transplant patients compared to normal controls.

Methods:

Four hundred twelve consecutive LN were evaluated (July 2007 to October 2018). Patients were divided into three groups (control, dialysis, and transplant). Perioperative outcomes, including operating room time (OT), postoperative complications, hospital length of stay, and 90-day readmission rates, were evaluated for the three groups.

Results:

There were 62 patients in the dialysis group, 20 renal transplants, and 330 normal controls. Dialysis patients were younger (median: 58 years versus 67 years; P = .002) and predominantly male (73% versus 59%, P = .047). Dialysis patients compared to controls had shorter total OT (median: 133 versus 149; P = .022), more papillary RCC (27% versus 10%; P < .001), and fewer high grade tumors (73% [8/11] versus 94% [100/106]; P = .038). Renal transplant patients had a higher rate of 90-day readmission (20% versus 6%; P = .034) and more papillary RCC (30% versus 10%; P = .016) compared to controls.

Conclusion:

LN on dialysis patients does not alter expected perioperative outcomes compared to a large cohort of control LN. LN on renal transplant patients carries a higher 90-day readmission rate than control LN.

Introduction

The average healthy individual's lifetime risk of developing renal cancer ranges between 1.3% and 1.8% in Europe and North America.¹ Like many cancers, certain factors have been identified that predispose a patient to develop renal cancer, such as male sex, African descendent, smoking, obesity, hypertension, end-stage renal disease (ESRD), older age, and organ transplantation.^1–4 ESRD and transplant impart a significantly increased risk of renal cancer development.^5,6 Renal cell carcinoma (RCC) in transplanted patients may be due to the preexistence of cancer cells in the native renal parenchyma before transplantation rather than de novo development while on immunosuppression therapy.⁷ Greater than 50% of patients on dialysis develop acquired cystic kidney disease (ACKD), which increases the likelihood to develop de novo RCC.¹ In the perioperative setting, patients on dialysis may be at increased risk of complications due to their compromised capability to adjust to the systemic response of the body during and after laparoscopic radical nephrectomy (LN).⁸ We sought to evaluate the perioperative outcomes of LN in patients on dialysis and those with renal transplant in place compared to a large LN cohort (controls).

Materials and Methods

Data collection

Following institutional review board approval, 412 consecutive patients who underwent LN at a single institution by a single surgeon were examined. LN was performed with the patient in the flank position utilizing a four port technique on the left side and a five port technique on the right side (extra port for liver retraction). All procedures were performed utilizing intraperitoneal approach. The renal hilum was sacrificed with endoscopic stapler in all cases, and kidneys were extracted from the abdomen after being placed in a laparoscopic sac. Nine patients underwent two LNs, but only the first operation was included in this study.

Of the 412 patients, 20 patients had a renal transplant in place, 62 were on dialysis, and 330 were considered normal controls. Demographic data (age, sex, and body mass index [BMI]) and preoperative characteristics (preoperative estimated glomerular filtration rate [eGFR] and Mayo Adhesive Probability [MAP] score⁹ in the tumor and contralateral kidneys) were collected. The MAP score was organized as low grade (0–3) and high grade (4–5).¹⁰ eGFR was calculated based on the MDRD 2006 formula.¹¹ Surgical and intraoperative outcomes such as operating room time (OT) and complications according to the Clavien–Dindo classifications were noted.¹² Postoperatively, every tumor underwent pathologic analysis to provide data on tumor size, grade, pathology, and malignant subtype if applicable. Length of stay (LOS) and readmissions within 90 days of surgery were also noted postoperatively. Prolonged LOS was classified as greater than 3 days of hospitalization.

Statistical analyses

Continuous variables were summarized with the sample median, 25th percentile, and 75th percentile. Categorical variables were summarized with the frequency and percentage of patients. We initially compared preoperative characteristics and surgical outcomes of dialysis and transplant patients to the normal controls using the Wilcoxon rank sum test for continuous data and the Fisher exact test for categorical data. For the primary aim of comparing surgical outcomes of dialysis and transplant patients to those of normal controls, the Holm step down method was used to correct for multiple testing for the 12 surgical outcomes separately for dialysis and transplant patients. P values less than .05 were considered statistically significant for all other analyses. All statistical tests were two sided. Statistical analyses were performed using SAS (version 9.4; SAS Institute, Inc., Cary, North Carolina).

Results

Preoperative characteristics

A total of 420 who underwent LN were included. Table 1 summarizes patient demographics. Dialysis patients tended to be younger (median: 58 years versus 67 years, P = .002) and predominantly male (45 [73%] versus 194 [59%]). The proportion of patients with a GFR >60 mL/min was lower in both dialysis patients (0%, P < .001) and transplant patients (42%; P = .045) compared to controls (66%). BMI was greater in the transplant group (32.1 [26.2, 35.4]). Among those patients on dialysis, 52 (84%) were on hemodialysis and 10 (16%) on peritoneal dialysis. There were no other statistically significant differences in preoperative characteristics in dialysis patients or transplant patients compared to controls.

Table 1.

Preoperative Characteristics

Variable	Normal (N = 330)	Dialysis (N = 62)	P value (D versus N)	Transplant (N = 20)	P value (T versus N)
Median age (IQR), y	67 (57, 75)	58 (53, 70)	.002	62 (50, 70)	.13
Sex, no. (%)
Female	136 (41)	17 (27)	.047	5 (25)	.17
Male	194 (59)	45 (73)	.047	15 (75)	.17
Median BMI (IQR), kg/m²	28.9 (25.2, 32.8)	29.5 (24.8, 32.5)	.66	32.1 (26.2, 35.4)	.10
GFR >60 mL/min, no. (%)	217/327 (66)	0/62 (0)	<.001	8/19 (42)	.05
MAP score in tumor kidney, no. (%)	N = 307	N = 62		N = 18
0–3	215 (70)	43 (69)	1.00	15 (83)	.29
4–5	92 (30)	19 (31)	1.00	3 (17)	.29
MAP score in contralateral kidney, no. (%)	N = 305	N = 59		N = 18
0–3	229 (75)	47 (80)	.51	15 (83)	.58
4–5	76 (25)	12 (20)	.51	3 (17)	.58

P values result from the Wilcoxon rank sum test for continuous data and the Fisher exact test for categorical data. The number of patients is given where a variable is missing for one or more patients.

BMI, body mass index; IQR, interquartile range; MAP, Mayo Adhesive Probability.

Surgical outcomes

Surgical outcomes are shown in Table 2. The median total OT (interquartile range [IQR], minutes) was lower in the dialysis population (133 minutes [108, 183], P = .02) compared to controls (149 minutes [123, 197]). There was no significant difference in complication rates in the dialysis cohort (P = .34) or in the transplant cohort (P = .08) compared with the normal population. In the dialysis cohort, minor postoperative complications (Grade 1–2) consisted mostly of low hemoglobin levels requiring blood transfusion and urinary retention or failed trial of void in both the dialysis cohort and control cohort. In the transplant cohort, minor postoperative complications consisted mostly of urinary retention and ileus.

Table 2.

Surgical Outcomes

Variable	Normal (N = 330)	Dialysis (N = 62)	P value (D versus N)	Transplant (N = 20)	P value (T versus N)
Median total operating room time (IQR), minutes	149 (123, 197)	133 (108, 183)	.022	134 (115, 192)	.47
Postop complication, no. (%)
None or Grade I–II	315 (95)	57 (92)	.34	17 (85)	.08
Grade III–V	15 (5)	5 (8)	.34	3 (15)	.08
Length of stay, no. (%)
1–3 days	277 (84)	48 (77)	.20	14 (70)	.12
4–29 days	53 (16)	14 (23)	.20	6 (30)	.12
90-Day readmission, no. (%)
No	311 (94)	57 (92)	.56	16 (80)	.03
Yes	19 (6)	5 (8)	.56	4 (20)	.03

IQR, interquartile range.

In the control cohort, 15 patients (5%) had major complications (Grade 3–5). The majority of those complications were related to cardiac and respiratory issues. Patients in the transplant group (3 [15%]) had greater postoperative complications of Grade III. There were no hospital deaths in the three groups. The transplant complications were all infectious in nature (sepsis, pneumonia, and Clostridium difficile infection). The dialysis patient complications were dialysis access issues (3), encephalopathy, and pneumonia.

Seven (11%) patients in the dialysis group, 29 (9%) in the normal group, and 1 (5%) in the transplant group went home on POD1. There was not a significant difference in prolonged LOS in the dialysis cohort (14 [23%], P = .20) or in the transplant cohort (6 [30%], P = .12) compared with the normal cohort (53 [16%]). Patients in the transplant group (4 [20%], P = .03) had higher rates of 90-day readmission compared with the normal cohort (19 [6%]). Conversion to open surgery occurred in 3 (1%) control patients, and 6 (2%) patients were converted to hand assisted surgery in the control group. There were no conversions to open surgery or hand assisted surgery in the dialysis or transplant groups.

Pathology findings

Table 3 summarizes pathology findings. The proportion of patients with smaller tumor size (<4 cm) was higher in the dialysis population (44 [80%], P < .01) and in the transplant population (12 [75%], P < .01) compared to controls (56 [20%]). There was evidence to suggest that dialysis patients (24 [39%], P = .03) and transplant patients (7 [35%], P = .04) had fewer clear cell RCC (ccRCC) compared to controls (197 [60%]). At the same time, transplant patients (6 [30%], P = .02) and dialysis patients (17 [27%], P < .01) had higher papillary RCC compared with the normal cohort (33 [10%]). After adjusting for multiple testing with the Holm step down method in the dialysis population (P < .0056 considered statistically significant), only tumor size, ccRCC, and papillary RCC were statistically significant. In the transplant cohort, only tumor size remains statistically significant after adjustment (P < .0045 considered statistically significant).

Table 3.

Pathology Findings

Variable	Normal (N = 283)	Dialysis (N = 55)	P value (D versus N)	Transplant (N = 16)	P value (T versus N)
Tumor size, no. (%)
<4 cm	56 (20)	44 (80)	<.001	12 (75)	<.01
4–7 cm	145 (51)	7 (13)		3 (19)
>7 cm	82 (29)	4 (7)		1 (6)
Pathology, no. (%)
Benign	70 (21)	14 (23)	.87	5 (25)	.78
Malignant	260 (79)	48 (77)	.87	15 (75)	.78
Malignant subtype, no. (%)
ccRCC	197 (60)	24 (39)	.003	7 (35)	.04
ccpRCC	1 (0)	2 (3)	.066	0 (0)	1.00
Papillary RCC	33 (10)	17 (27)	<.001	6 (30)	.02
Chromophobe RCC	19 (6)	2 (3)	.55	1 (5)	1.00
Other malignancy	10 (3)	3 (5)	.44	1 (5)	.48
Tumor grade	N = 106	N = 11		N = 7
Low (1–2), no. (%)	6 (6)	3 (27)	.038	1 (14)	.37
High (3–4), no. (%)	100 (94)	8 (73)	.038	6 (86)	.37

ccRCC, clear cell renal cell carcinoma; ccpRCC, clear cell papillary renal cell carcinoma; RCC, renal cell carcinoma.

Discussion

The detection of renal masses in patients who are on dialysis or had a previous renal transplant is not uncommon. It has been well studied that ACKD is a common development in dialysis patients with chronic kidney disease and in patients taking immunosuppression after transplantation.¹³ In particular, ACKD contributes substantially as a risk factor for cystic RCC development.¹⁴ Partial and radical nephrectomies are commonly used for the treatment of renal masses. LN has emerged as an alternative to open nephrectomy in patients with RCC.¹⁵ Postoperative complications that ensue from LN, regardless of transplant or dialysis status, can include bleeding, cardiovascular events, infections, and gastrointestinal complications.¹⁶ In addition, the utilization of LN has been suggested to offer shorter LOS and possibly fewer intraoperative and postoperative complications.¹⁷

Multiple studies have suggested that dialysis patients have an increased risk for complications during the perioperative period.^14,18 These large studies were conducted with data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP). May et al. evaluated 445 patients with a history of dialysis who developed renal masses and underwent LN.¹⁴ It was determined that patients who went for dialysis 2 weeks before LN had significantly increased risk for more minor (14.6% versus 8.1%, P < .0001) and major (4.5% versus 2.1%, P = .0025) postoperative complications, longer LOS (mean: 4.2 days versus 3.3 days, P < .0001), and more unplanned readmissions (3.8% versus 1.7%, P = .002) compared to nondialysis patients.¹⁴ However, in our study, there was no significant difference in postoperative complications for LN in dialysis patients. Keehn et al. similarly studied dialysis patients following LN within a single surgeon series. They found dialysis patients to be younger (P = .004) and have smaller tumors (P = .0001) than the control cohort. Operating room time (OT) was shorter (P = .4) than the control cohort but not statistically significant.¹⁹ They also found that the dialysis group did not differ from the control group in postoperative complications and LOS. Their results differed from our data in that the prevalence of papillary RCC was higher in the dialysis group but was not statistically significant.¹⁹

Chebib et al. conducted a study that aimed to evaluate indications, timing, and postoperative complications between the surgical techniques (open or laparoscopic) in autosomal-dominant polycystic kidney disease of 114 transplant recipients that underwent pretransplant or post-transplant nephrectomy.²⁰ Complications were less common in those who underwent nephrectomy post-transplant (26.6% versus 48%; P = .03), but were similar regardless of surgical technique (open, 33.3% versus laparoscopic, 33%; P = .66). Median LOS was shorter in the post-transplant group compared to those patients with pretransplant nephrectomy (4 days versus 6 days; P < .001).²⁰

We found that the total OT was significantly shorter in the dialysis cohort compared with the control group (P = .022). We propose that this shorter total OT in the dialysis cohort can be attributed to the atrophic kidneys and the smaller renal masses in the dialysis patient population (P < .001). Patients on dialysis are more routinely monitored, resulting in greater detections and abnormalities in renal anatomy compared to patients who do not have renal insufficiency and perhaps this is the reason for smaller tumor detection.

Interestingly, the results from our study suggest that malignant subtypes significantly differed. In our study, papillary RCC was significantly more common in the dialysis group (N = 17, 27%) and the transplant group (N = 6, 30%) compared to the normal cohort (N = 197, 6%) (P < .001 and P = .016, respectively), and ccRCC was significantly less frequently observed in the dialysis group (N = 24, 39%) and in the transplant group (N = 7, 35%). Previous studies found that ccRCC had higher incidence rates in transplant and dialysis patients.^16,19,21,22 Still, Kellerman and Karami et al. support our finding that papillary RCC is more common in patients with ESRD who are on dialysis.^23,24

The main limitation to this study is its retrospective nature that limits the ability to accurately account for all possible factors influencing the development of renal masses. Other limitations include short follow-up and no evaluation of the immunosuppressant status. There is also absence of outcome evaluations of hemodialysis patients versus peritoneal dialysis patients. In addition, this was a single-surgeon series which may not take our findings as widely applicable for all surgeons. The strength of this study is that it is a large single surgeon series that eliminates operative technique as a variable in the analysis.

Conclusions

Patients on dialysis can safely undergo LN to treat renal masses with perioperative outcomes similar to normal controls. LN in renal transplant patients is associated with an increased 90-day readmission rate.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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