CLINICAL
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TRANSLATIONAL RESEARCH
Ureteral Complications After Hand-Assisted Laparoscopic Living Donor Nephrectomy Ahmed H. Gabr,1 Randall S. Sung,2 Milagros D. Samaniego-Picota,3 Chang He,4 and J. Stuart Wolf, Jr4,5 Background. Urological complications, namely ureteral leak and obstruction, remain a major source of morbidity after renal transplantation. Given that the existing literature on ureteral complications pertains mostly to deceased as opposed to living donors, we aimed to assess the risk factors for ureteral complications solely after living donor nephrectomy. Methods. We identified 480 consecutive cases of renal transplantation after hand-assisted laparoscopic living donor nephrectomy at our institution from January 2008 to February 2013. We determined the incidence of ureteral complications and assessed the association with a number of perioperative factors, including age, sex, race, and body mass index of both the donor and recipient; arterial and ureteral anatomy; procurement by transplant surgeon versus urologist; history of previous renal transplantations; technique of ureteral anastomosis; use of ureteral stent; total ischemia time; serum creatinine on discharge; and need for temporary posttransplant hemodialysis. Results. Among 480 renal transplantations after living donor nephrectomy, ureteral complications occurred in 18 (3.7%), including ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors were significantly associated with ureteral complications on multivariate analysis: increased donor age and no placement of ureteral stent. Conclusions. Ureteral complications of renal transplants after living donor nephrectomy are uncommon. The use of a ureteral stent is protective against ureteral complications and increased donor age is associated with an increased incidence of ureteral complications. Keywords: Laparoscopy, Nephrectomy, Renal transplantation. (Transplantation 2014;97: 788Y792)
enal transplantation is viewed as the best solution for patients with end-stage renal failure with the ultimate goal of restoring renal function in such patients. Nonetheless, the potential risks of the procedure and subsequent management are not trivial. Urological complications, namely ureteral leak and obstruction, remain one of the major sources of morbidity related to the surgical procedure itself. The general incidence of urologic complications among different series,
R
This study received funding from the University of Michigan. The authors declare no conflicts of interest. 1 Department of Urology, Minia University, Egypt. 2 Department of Surgery, Section of Transplantation Surgery, University of Michigan Health System, Ann Arbor, MI. 3 Department of Internal Medicine, Division of Nephrology, University of Michigan Health System, Ann Arbor, MI. 4 Department of Urology, University of Michigan Health System, Ann Arbor, MI. 5 Address correspondence to: J. Stuart Wolf Jr, M.D., Department of Urology, University of Michigan, 3875 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0330. E-mail: [email protected] A.H.G. and J.S.W.J. participated in designing the research, writing the article, performing the research, and analyzing the data. R.S.S. and M.D.S.-P. participated in the writing the article. C.H. participated in designing the research and analyzing the data. Received 12 August 2013. Revision requested 28 August 2013. Accepted 10 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9707-788 DOI: 10.1097/01.TP.0000437559.41514.96
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whether associated with living or deceased donors, ranges between 2.5% and 30%; although in the most recent series, the rate is less than 10% (1, 2). Since Ratner et al. (3) reported laparoscopic live donor nephrectomy (LLDN) from a 40-year-old man in 1995, the use of laparoscopy for donor nephrectomy has progressively increased. There is increasing use of living donor kidneys overall, from 20.5% of all kidney transplants in 1988 to 35% in 2013 as reported by the Organ Procurement and Transplantation Network (4). Indeed, improvement of the laparoscopy learning curve is associated with better outcome (5Y7) and subsequently increased usage of living donor kidneys. Some literature suggests that the urologic complication rate after living donor transplantation is similar to that after deceased donor transplantation (1, 2), but other works suggest that the urologic complication rate may be lower after living compared to deceased donor transplantation (8Y11). Given this possible different incidence of urologic complications in living compared to deceased donors, and given that the existing literature on ureteral complications pertains mostly to deceased donors, we aimed to evaluate the risk factors for ureteral complications (ureteral leak and stricture) solely after LLDN.
RESULTS Of 480 LLDN patients, 303 (63%) were females and 177 (37%) were males with a mean age of 42 years (range, 18Y68 yr). They had a mean body mass index (BMI) of 27.4 kg/m2 (range, Transplantation
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17.2Y39.9 kg/m2). Nephrectomy was performed on the left side in 426 donors and on the right side in 54 donors. Of the donors, 210 were related and 270 were unrelated. White donors constituted 78% of the donors. One urologist performed 67 nephrectomies, and all others were performed by one of seven transplant surgeons. Of the LLDNs, two were converted to open surgery. There was not a ureteral complication in either of the recipients of these two kidneys. Mean cold ischemia time (cold perfusion to starting implantation) was 125 min (range, 19Y597 min), and mean warm ischemia time (start to completion of implantation) was 31 min (range, 7Y91 min). Of the recipients, 158 (33%) were females and 322 (67%) were males. Their mean age was 46 years (range, 1Y75 yr), and mean BMI was 29.6 kg/m2 (range, 12.8Y48.7 kg/m2). Transplantation was performed on the right side in 189 patients (39%) and on the left side in 291 patients (61%). Of the recipients, 387 (81%) were white. External ureteroneocystostomy was used in 465 recipients (97%), while Leadbetter-Politano and ileal loop implantations were used in 9 (1.9%) and 6 (1.2%) patients, respectively. A ureteral stent was placed in 456 (95%) of the transplanted kidneys. Of the recipients, 27 (5.6%) had a serum creatinine greater than 3 mg/dL at the time of discharge. The rate of ureteral complications after transplantation was 18 (3.7%), including ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors were significantly associated with ureteral complications on bivariate analysis: increased donor age (6.1% rate for donors 9 median age of 43 yr vs. 1.28% for donors G median age, P=0.0168) and no placement of ureteral stent (25% rate if no stent was used vs. 2.6% if stent was used, P=0.0002). Tables 1 and 2 illustrate the factors and their relation to the incidence of ureteral complications. For multivariate analyses (Table 3), owing to the small number of ureteral complications, only four factors were included in the assessment: donor age, donor BMI, recipient sex, and placement of ureteral stent. Donor BMI and recipient sex were not associated with ureteral complications on the multivariate analysis. Increased donor age remained associated with the occurrence of a ureteral complication, with an odds ratio of 1.058. Thus, for each added year of age of the donor, the odds of a ureteral complication increases 5.8%. Omission of a ureteral stent also remained associated with ureteral complications, with an odds ratio of 10.593, suggesting a greater than 10-fold increased odds of having a ureteral complication when a stent is omitted. Of the 24 transplants managed without placement of a ureteral stent, 6 (25%) suffered a ureteral complication, compared to a 2.6% incidence in the 456 transplants in which a ureteral stent was placed (Table 1).
DISCUSSION Recently, laparoscopy has become the preferred technique for living donor nephrectomy, especially in large centers with large experience in laparoscopic renal surgery (12). Among different studies, the rate of complications of LLDN ranged from 6% to 29% (13). Much of this wide range is likely attributable to variations in reporting; some authors include lymphocele and others also include urinary tract infections. Ureteral leaks and strictures, however, are the most common major urological complications after LLDN.
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In the present study, ureteral complications are significantly related to the donor’s age and omission of a ureteral stent. Recipient age has been found to be a risk factor for ureteral complications in some studies (9, 14). Specifically, an increased rate of complications in the youngest recipients was found. In our cohort, the age of the recipient was not associated with ureteral complications, but the age of the donor was associated, with older donors having a greater risk. Although several series suggest that increased age of living donors is associated with poorer long-term graft survival (15Y18), to our knowledge, ours is the first study to suggest that increased donor age is associated with increased incidence of ureteral complications. The factor that seems to have the greatest impact on the increasing ureteral complication rate is omission of a ureteral stent. A ureteral stent was placed in 95% of renal transplants, and in these patients, the ureteral complication rate was 2.6%. Among the 24 transplants managed without placement of a ureteral stent, 6 (25%) suffered a ureteral complication. The protective effect of ureteral stent placement has been confirmed in a meta-analysis of randomized clinical trials (19) and seems to be a cost-effective strategy (20). The lack of ureteral stent placement in 5% of our cohort based on surgeon judgment needs to be reevaluated in light of this meta-analysis and the findings of our current study. In their retrospective study, Englesbe et al. (8) found that male recipients had a greater incidence of ureteral complications. The same observation was noted by Rigg et al. (9), who reported an increased occurrence of ureteral leaks in male recipients. In our study, there was no association between recipient sex and ureteral complications. In addition, we did not find race to be significantly associated with ureteral complications, either for the donor or for the recipient. This was in contrast to other studies that found that African American recipients are more likely to suffer from ureteral complications (8). Some have proposed that maintaining the gonadal vein along with the ureter during nephrectomy might ensure preservation of the periureteral tissue and therefore improve ureteral blood flow and reduce ureteral complications (6), although other authors have disputed this (21). In our institution, urologists maintain the gonadal vein with the ureter, whereas the transplant surgeons do not. Although our analysis might be biased by other unknown factors, we found no difference in the incidence of ureteral complications after urologist versus transplant surgeon renal procurement, so it seems likely that maintaining the gonadal vein with the ureter during LLDN does not improve outcomes. It might be possible that preservation of the gonadal vein is important in patients ‘‘at risk’’ for ureteral complications, such as older donors. We explored this with our data by evaluating the subset of patients 43 years or older (above the median). Among this group, 16% of LLDN cases not associated with ureteral complications were performed by the urologist, similar to the 25% of LLDN cases associated with ureteral complications (Fisher exact test, P=0.1133). Thus, even in older donors, maintaining the gonadal vein with the ureter during LLDN does not improve outcomes. We could not address more specific surgeon-level differences owing to the large number of surgeons involved (8) relative to the number of events (18). Of note, however, 5 of the 7 transplant surgeons were associated with
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TABLE 1.
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Bivariate logistic regression analyses
Factor Experience First tertile Second tertile Third tertile Donor sex Female Male Donor race Other White or Caucasian Donor type Living related Living nonrelated Kidney side Left Right Surgeon type Transplant surgeon Urologist Arterial anatomy Multiple Single Ureteral anatomy Double Single Recipient sex Female Male Recipient race Other White or Caucasian Transplantation no. 1 2 3 4 Ureteral anastomosis External ureteroneocystostomy Ileal loop Leadbetter-Politano Use of ureteral stent No Yes Creatinine at discharge 93 No Yes Temporary posttreatment dialysis No Yes
No. with factor
% with ureteral complication
Odds ratio
95% CL
P
160 160 160
4.4 5.0 1.9
2.388 2.746 V
0.533Y14.571 0.644Y16.370 Y
0.3359 0.2184 V
303 177
4.0 3.4
1.175 V
0.399Y3.887 Y
0.9621 V
108 372
3.7 3.8
0.984 V
0.231Y3.221 Y
1.000 V
210 270
2.9 4.4
0.633 V
0.191Y1.860 Y
0.5101 V
424 54
4.3 0
3.357 V
0.564Yinfinity Y
0.2217 V
413 67
3.4 6
0.553 V
0.167Y2.383 Y
0.4674 V
118 362
1.7 4.4
0.373 V
0.041Y1.626 Y
0.2782 V
4 476
0 3.8
4.892 V
158 322
1.9 4.7
0.397 V
0.073Y1.433 Y
0.2077 V
93 387
3.2 3.9
0.827 V
0.150Y3.013 Y
1.0000 V
418 58 3 1
3.8 3.5 0 0
0.040 0.035 V V
0.001Yinfinity G0.001Yinfinity Y Y
1.0000 1.0000 V V
465 6 9
3.7 16.7 0
0.464 1.500 V
0.069Yinfinity 0.038Yinfinity Y
1.0000 0.8000 V
24 456
25 2.6
10.912 V
3.042Y 35.580 Y
0.0002 V
453 27
3.5 7.4
0.459 V
0.099Y4.333 Y
0.5370 V
471 9
3.8 0
0.487 V
0.072Yinfinity Y
1.0000 V
0Y40.772 Y
CL, confidence limit.
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1.0000 V
Gabr et al.
* 2014 Lippincott Williams & Wilkins
the 14 ureteral complications after LLDN not performed by the urologist, and ureteral complications occurred after at least 1 kidney transplantation was performed by each of the 7 transplant surgeons. The primary limitation of this study is its retrospective design, which exposes the analysis to unknown bias. In addition, the small number of events (ureteral complications) limited the factors that could be assessed with the multivariate analysis. In summary, ureteral complications after LLDN are uncommon. Our study confirmed that the use of a ureteral stent is protective, as has been well demonstrated in randomized controlled trials. The only other factor associated with ureteral complications after LLDN is donor age, with increased donor age being associated with increased incidence of ureteral complications. We were unable to identify any other factors associated with the incidence of ureteral complications.
MATERIALS AND METHODS From our institutional review boardYapproved prospective database, we identified 480 consecutive cases of renal transplantation after hand-assisted LLDN in the period from January 2008 to February 2013. There were no planned open surgical donor nephrectomies done during this period. We selected this period because only after January 2008 were ureteral complications reliably entered into the database prospectively. Cases were subdivided into three time-based tertiles (i.e., first 160 cases, second 160 cases, and third 160 cases), as a surrogate for surgeon and institutional experience. All renal donors were evaluated by a transplant nephrologist and a transplant surgeon. Standard donor evaluation was applied (12), including computed tomography or magnetic resonance imaging with angiographic phase to define the exact renal anatomy. Laparoscopic donor nephrectomy was performed using a hand-assisted approach, with two or three additional laparoscopic ports. The attending
TABLE 2. Bivariate regression analyses (reported above and below median) No. (%) with ureteral Odds complication ratio
Factor (Q or Gmedian)a Donor age (yr) Q43 G43 Donor BMI (kg/m2) Q26.85 G26.85 Total ischemia (min) Q144 G144 Recipient age (yr) Q49 G49 Recipient BMI (kg/m2) Q27.60 G27.60
95% CL
P
1.009 1.009Y1.106 0.0168 15 (6.10) 3 (1.28) 1.099 0.986Y1.225 0.0875 10 (4.26) 7 (2.98)
TABLE 3.
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Multivariate regression analysis
Factor
Odds ratio 95% confidence limit
Increased donor age Increased donor BMI Male recipient No ureteral stent
1.058 1.118 3.463 10.593
1.005Y1.113 0.991Y1.261 0.765Y15.669 3.131Y35.840
P 0.0301 0.0690 0.0994 0.0001
BMI, body mass index.
surgeons included seven transplant (general) surgeons and one urologist, all fellowship trained. Over time, the procedure has become standardized (6), with some minor variations between surgeons with regard to instrumentation and technique of handling the ureter. In all cases, the donated kidney was initially prepared with cold perfusion and packaging as per the United Network for Organ Sharing protocol. Renal transplantation was performed by one of seven transplant surgeons using an extraperitoneal open surgical approach, with vascular anastomoses to the iliac vessels for adult recipients. The surgeon performing the transplant was not necessarily the same performing the LLDN. The method used to establish ureteral anastomosis to the urinary bladder was extravesical ureterocystostomy (modified Lich-Gregoir technique) or intravesical ureterocystostomy (Politano-Leadbetter technique). In no case was the donor ureter anastomosed to the recipient ureter. In a few cases, the ureter was connected to a previously created ileal conduit. Ureteral stents were placed at the discretion of the operating surgeon; stents were placed routinely by the majority of surgeons but selectively by others. Study data collected regarding the renal donor included age, sex, race, type (living related or unrelated), BMI, side of kidney removed (left or right), arterial anatomy, ureteral anatomy, and total ischemia time. This is in addition to the category of surgeon, that is, transplant surgeon versus urologist. Study data collected regarding the recipient included age, sex, race, BMI, history of prior renal transplantation, technique of ureteral anastomosis, use of ureteral stent, serum creatinine on discharge, and need for temporary posttransplant hemodialysis. During the postoperative period, staff regularly reviewed the medical record to ascertain the presence or absence of ureteral complications. All cases in which ureteral complications were reported underwent review by the first author to confirm ureteral leak or ureteral stricture. Owing to their low incidence, we analyzed ureteral complications as a whole, without subgroup analysis for leaks or strictures. To determine the bivariate association of donor and recipient factors with ureteral complications, we used exact logistic regression analysis to take into account the small number of ureteral complication events. For multivariable analysis, we performed backward model building procedure to determine significant clinical predictors for the incidence of ureteral complications. Associations between predictors and the outcome are shown as odds ratios with 95% confidence limits. Statistical analyses were performed using SAS version 9.2 software (SAS Institute, Cary, NC).
1.000 1.000Y1.000 0.5697 11 (4.64) 7 (2.95)
REFERENCES 0.996 0.967Y1.026 0.7696
10 (4.17) 8 (3.43) 1.003 0.944Y1.038 0.7193 8 (3.35) 10 (4.20)
a These values are given for illustration only; the odds ratios, 95% confidence limits (CL), and P values are derived from the analysis of continuous variables. BMI, body mass index.
1.
2.
3. 4.
Alberts VP, Minnee RC, Bemelman FJ, et al. Ureteral reconstruction after renal transplantation: clinical outcome and risk factors. Urol Int 2012; 88: 333. Saeb-Parsy K, Kosmoliaptsis V, Sharples LD, et al. Donor type does not influence the incidence of major urologic complications after kidney transplantation. Transplantation 2010; 90: 1085. Ratner LE, Ciseck LJ, Moore RG, et al. Laparoscopic live donor nephrectomy. Transplantation 1995; 60: 1047. Organ Procurement and Transplantation. Donors eecovered in the U.S. by donor type. Organ Procurement and Transplantation Network. 2013. Available at: http://optn.transplant.hrsa.gov/latestData/rptData.asp. Accessed May 12, 2013.
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792 5. 6. 7. 8. 9. 10. 11. 12.
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Chin EH, Hazzan D, Herron DM, et al. Laparoscopic donor nephrectomy: intraoperative safety, immediate morbidity, and delayed complications with 500 cases. Surg Endosc 2007; 21: 521. Fisher PC, Montgomery JS, Johnston WK 3rd, et al. 200 consecutive hand assisted laparoscopic donor nephrectomies: evolution of operative technique and outcomes. J Urol 2006; 175: 1439. Su LM, Ratner LE, Montgomery RA, et al. Laparoscopic live donor nephrectomy: trends in donor and recipient morbidity following 381 consecutive cases. Ann Surg 2004; 240: 358. Englesbe MJ, Dubay DA, Gillespie BW, et al. Risk factors for urinary complications after renal transplantation. Am J Transplant 2007; 7: 1536. Rigg KM, Proud G, Taylor RM. Urological complications following renal transplantation. A study of 1016 consecutive transplants from a single centre. Transpl Int 1994; 7: 120. Faenza A, Nardo B, Catena F, et al. Ureteral stenosis after kidney transplantation. Transpl Int 1999; 12: 334. Minnee RC, Bemelman FJ, Laguna Pes PP, et al. Effectiveness of a 5-day external stenting protocol on urological complications after renal transplantation. World J Surg 2009; 33: 2722. Friedersdorff F, Werthemann P, Cash H, et al. Outcomes after laparoscopic living donor nephrectomy: comparison of two laparoscopic surgeons with different levels of expertise. BJU Int 2013; 111: 95.
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Harper JD, Breda A, Leppert JT, et al. Experience with 750 consecutive laparoscopies donor nephrectomiesYis it time to use a standardized classification of complications? J Urol 2010; 183: 1941. El-Mekresh M, Osman Y, Ali-El-Dein B, et al. Urological complications after living-donor renal transplantation. BJU Int 2001; 87: 295. Balachandran VP, Aull MJ, Charlton M, et al. Kidneys from older living donors provide excellent intermediate-term outcomes after transplantation. Transplantation 2012; 94: 499. Naumovic R, Djukanovic L, Marinkovic J, et al. Effect of donor age on the outcome of living-related kidney transplantation. Transpl Int 2005; 18: 1266. Gill JS, Gill J, Rose C, et al. The older living kidney donor: part of the solution to the organ shortage. Transplantation 2006; 82: 1662. Iordanous Y, Seymour N, Young A, et al. Recipient outcomes for expanded criteria living kidney donors: the disconnect between current evidence and practice. Am J Transplant 2009; 9: 1558. Mangus RS, Haag BW. Stented versus nonstented extravesical ureteroneocystostomy in renal transplantation: a metaanalysis. Am J Transplant 2004; 4: 1889. DuBay DA, Lynch R, Cohn J, et al. Is routine ureteral stenting costeffective in renal transplantation? J Urol 2007; 178: 2509. Breda A, Bui MH, Liao JC, et al. Incidence of ureteral strictures after laparoscopic donor nephrectomy. J Urol 2006; 176: 1065.
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AND
TRANSLATIONAL RESEARCH
Ureteral Complications After Hand-Assisted Laparoscopic Living Donor Nephrectomy Ahmed H. Gabr,1 Randall S. Sung,2 Milagros D. Samaniego-Picota,3 Chang He,4 and J. Stuart Wolf, Jr4,5 Background. Urological complications, namely ureteral leak and obstruction, remain a major source of morbidity after renal transplantation. Given that the existing literature on ureteral complications pertains mostly to deceased as opposed to living donors, we aimed to assess the risk factors for ureteral complications solely after living donor nephrectomy. Methods. We identified 480 consecutive cases of renal transplantation after hand-assisted laparoscopic living donor nephrectomy at our institution from January 2008 to February 2013. We determined the incidence of ureteral complications and assessed the association with a number of perioperative factors, including age, sex, race, and body mass index of both the donor and recipient; arterial and ureteral anatomy; procurement by transplant surgeon versus urologist; history of previous renal transplantations; technique of ureteral anastomosis; use of ureteral stent; total ischemia time; serum creatinine on discharge; and need for temporary posttransplant hemodialysis. Results. Among 480 renal transplantations after living donor nephrectomy, ureteral complications occurred in 18 (3.7%), including ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors were significantly associated with ureteral complications on multivariate analysis: increased donor age and no placement of ureteral stent. Conclusions. Ureteral complications of renal transplants after living donor nephrectomy are uncommon. The use of a ureteral stent is protective against ureteral complications and increased donor age is associated with an increased incidence of ureteral complications. Keywords: Laparoscopy, Nephrectomy, Renal transplantation. (Transplantation 2014;97: 788Y792)
enal transplantation is viewed as the best solution for patients with end-stage renal failure with the ultimate goal of restoring renal function in such patients. Nonetheless, the potential risks of the procedure and subsequent management are not trivial. Urological complications, namely ureteral leak and obstruction, remain one of the major sources of morbidity related to the surgical procedure itself. The general incidence of urologic complications among different series,
R
This study received funding from the University of Michigan. The authors declare no conflicts of interest. 1 Department of Urology, Minia University, Egypt. 2 Department of Surgery, Section of Transplantation Surgery, University of Michigan Health System, Ann Arbor, MI. 3 Department of Internal Medicine, Division of Nephrology, University of Michigan Health System, Ann Arbor, MI. 4 Department of Urology, University of Michigan Health System, Ann Arbor, MI. 5 Address correspondence to: J. Stuart Wolf Jr, M.D., Department of Urology, University of Michigan, 3875 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0330. E-mail: [email protected] A.H.G. and J.S.W.J. participated in designing the research, writing the article, performing the research, and analyzing the data. R.S.S. and M.D.S.-P. participated in the writing the article. C.H. participated in designing the research and analyzing the data. Received 12 August 2013. Revision requested 28 August 2013. Accepted 10 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9707-788 DOI: 10.1097/01.TP.0000437559.41514.96
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whether associated with living or deceased donors, ranges between 2.5% and 30%; although in the most recent series, the rate is less than 10% (1, 2). Since Ratner et al. (3) reported laparoscopic live donor nephrectomy (LLDN) from a 40-year-old man in 1995, the use of laparoscopy for donor nephrectomy has progressively increased. There is increasing use of living donor kidneys overall, from 20.5% of all kidney transplants in 1988 to 35% in 2013 as reported by the Organ Procurement and Transplantation Network (4). Indeed, improvement of the laparoscopy learning curve is associated with better outcome (5Y7) and subsequently increased usage of living donor kidneys. Some literature suggests that the urologic complication rate after living donor transplantation is similar to that after deceased donor transplantation (1, 2), but other works suggest that the urologic complication rate may be lower after living compared to deceased donor transplantation (8Y11). Given this possible different incidence of urologic complications in living compared to deceased donors, and given that the existing literature on ureteral complications pertains mostly to deceased donors, we aimed to evaluate the risk factors for ureteral complications (ureteral leak and stricture) solely after LLDN.
RESULTS Of 480 LLDN patients, 303 (63%) were females and 177 (37%) were males with a mean age of 42 years (range, 18Y68 yr). They had a mean body mass index (BMI) of 27.4 kg/m2 (range, Transplantation
& Volume 97, Number 7, April 15, 2014
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* 2014 Lippincott Williams & Wilkins
17.2Y39.9 kg/m2). Nephrectomy was performed on the left side in 426 donors and on the right side in 54 donors. Of the donors, 210 were related and 270 were unrelated. White donors constituted 78% of the donors. One urologist performed 67 nephrectomies, and all others were performed by one of seven transplant surgeons. Of the LLDNs, two were converted to open surgery. There was not a ureteral complication in either of the recipients of these two kidneys. Mean cold ischemia time (cold perfusion to starting implantation) was 125 min (range, 19Y597 min), and mean warm ischemia time (start to completion of implantation) was 31 min (range, 7Y91 min). Of the recipients, 158 (33%) were females and 322 (67%) were males. Their mean age was 46 years (range, 1Y75 yr), and mean BMI was 29.6 kg/m2 (range, 12.8Y48.7 kg/m2). Transplantation was performed on the right side in 189 patients (39%) and on the left side in 291 patients (61%). Of the recipients, 387 (81%) were white. External ureteroneocystostomy was used in 465 recipients (97%), while Leadbetter-Politano and ileal loop implantations were used in 9 (1.9%) and 6 (1.2%) patients, respectively. A ureteral stent was placed in 456 (95%) of the transplanted kidneys. Of the recipients, 27 (5.6%) had a serum creatinine greater than 3 mg/dL at the time of discharge. The rate of ureteral complications after transplantation was 18 (3.7%), including ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors were significantly associated with ureteral complications on bivariate analysis: increased donor age (6.1% rate for donors 9 median age of 43 yr vs. 1.28% for donors G median age, P=0.0168) and no placement of ureteral stent (25% rate if no stent was used vs. 2.6% if stent was used, P=0.0002). Tables 1 and 2 illustrate the factors and their relation to the incidence of ureteral complications. For multivariate analyses (Table 3), owing to the small number of ureteral complications, only four factors were included in the assessment: donor age, donor BMI, recipient sex, and placement of ureteral stent. Donor BMI and recipient sex were not associated with ureteral complications on the multivariate analysis. Increased donor age remained associated with the occurrence of a ureteral complication, with an odds ratio of 1.058. Thus, for each added year of age of the donor, the odds of a ureteral complication increases 5.8%. Omission of a ureteral stent also remained associated with ureteral complications, with an odds ratio of 10.593, suggesting a greater than 10-fold increased odds of having a ureteral complication when a stent is omitted. Of the 24 transplants managed without placement of a ureteral stent, 6 (25%) suffered a ureteral complication, compared to a 2.6% incidence in the 456 transplants in which a ureteral stent was placed (Table 1).
DISCUSSION Recently, laparoscopy has become the preferred technique for living donor nephrectomy, especially in large centers with large experience in laparoscopic renal surgery (12). Among different studies, the rate of complications of LLDN ranged from 6% to 29% (13). Much of this wide range is likely attributable to variations in reporting; some authors include lymphocele and others also include urinary tract infections. Ureteral leaks and strictures, however, are the most common major urological complications after LLDN.
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In the present study, ureteral complications are significantly related to the donor’s age and omission of a ureteral stent. Recipient age has been found to be a risk factor for ureteral complications in some studies (9, 14). Specifically, an increased rate of complications in the youngest recipients was found. In our cohort, the age of the recipient was not associated with ureteral complications, but the age of the donor was associated, with older donors having a greater risk. Although several series suggest that increased age of living donors is associated with poorer long-term graft survival (15Y18), to our knowledge, ours is the first study to suggest that increased donor age is associated with increased incidence of ureteral complications. The factor that seems to have the greatest impact on the increasing ureteral complication rate is omission of a ureteral stent. A ureteral stent was placed in 95% of renal transplants, and in these patients, the ureteral complication rate was 2.6%. Among the 24 transplants managed without placement of a ureteral stent, 6 (25%) suffered a ureteral complication. The protective effect of ureteral stent placement has been confirmed in a meta-analysis of randomized clinical trials (19) and seems to be a cost-effective strategy (20). The lack of ureteral stent placement in 5% of our cohort based on surgeon judgment needs to be reevaluated in light of this meta-analysis and the findings of our current study. In their retrospective study, Englesbe et al. (8) found that male recipients had a greater incidence of ureteral complications. The same observation was noted by Rigg et al. (9), who reported an increased occurrence of ureteral leaks in male recipients. In our study, there was no association between recipient sex and ureteral complications. In addition, we did not find race to be significantly associated with ureteral complications, either for the donor or for the recipient. This was in contrast to other studies that found that African American recipients are more likely to suffer from ureteral complications (8). Some have proposed that maintaining the gonadal vein along with the ureter during nephrectomy might ensure preservation of the periureteral tissue and therefore improve ureteral blood flow and reduce ureteral complications (6), although other authors have disputed this (21). In our institution, urologists maintain the gonadal vein with the ureter, whereas the transplant surgeons do not. Although our analysis might be biased by other unknown factors, we found no difference in the incidence of ureteral complications after urologist versus transplant surgeon renal procurement, so it seems likely that maintaining the gonadal vein with the ureter during LLDN does not improve outcomes. It might be possible that preservation of the gonadal vein is important in patients ‘‘at risk’’ for ureteral complications, such as older donors. We explored this with our data by evaluating the subset of patients 43 years or older (above the median). Among this group, 16% of LLDN cases not associated with ureteral complications were performed by the urologist, similar to the 25% of LLDN cases associated with ureteral complications (Fisher exact test, P=0.1133). Thus, even in older donors, maintaining the gonadal vein with the ureter during LLDN does not improve outcomes. We could not address more specific surgeon-level differences owing to the large number of surgeons involved (8) relative to the number of events (18). Of note, however, 5 of the 7 transplant surgeons were associated with
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TABLE 1.
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Bivariate logistic regression analyses
Factor Experience First tertile Second tertile Third tertile Donor sex Female Male Donor race Other White or Caucasian Donor type Living related Living nonrelated Kidney side Left Right Surgeon type Transplant surgeon Urologist Arterial anatomy Multiple Single Ureteral anatomy Double Single Recipient sex Female Male Recipient race Other White or Caucasian Transplantation no. 1 2 3 4 Ureteral anastomosis External ureteroneocystostomy Ileal loop Leadbetter-Politano Use of ureteral stent No Yes Creatinine at discharge 93 No Yes Temporary posttreatment dialysis No Yes
No. with factor
% with ureteral complication
Odds ratio
95% CL
P
160 160 160
4.4 5.0 1.9
2.388 2.746 V
0.533Y14.571 0.644Y16.370 Y
0.3359 0.2184 V
303 177
4.0 3.4
1.175 V
0.399Y3.887 Y
0.9621 V
108 372
3.7 3.8
0.984 V
0.231Y3.221 Y
1.000 V
210 270
2.9 4.4
0.633 V
0.191Y1.860 Y
0.5101 V
424 54
4.3 0
3.357 V
0.564Yinfinity Y
0.2217 V
413 67
3.4 6
0.553 V
0.167Y2.383 Y
0.4674 V
118 362
1.7 4.4
0.373 V
0.041Y1.626 Y
0.2782 V
4 476
0 3.8
4.892 V
158 322
1.9 4.7
0.397 V
0.073Y1.433 Y
0.2077 V
93 387
3.2 3.9
0.827 V
0.150Y3.013 Y
1.0000 V
418 58 3 1
3.8 3.5 0 0
0.040 0.035 V V
0.001Yinfinity G0.001Yinfinity Y Y
1.0000 1.0000 V V
465 6 9
3.7 16.7 0
0.464 1.500 V
0.069Yinfinity 0.038Yinfinity Y
1.0000 0.8000 V
24 456
25 2.6
10.912 V
3.042Y 35.580 Y
0.0002 V
453 27
3.5 7.4
0.459 V
0.099Y4.333 Y
0.5370 V
471 9
3.8 0
0.487 V
0.072Yinfinity Y
1.0000 V
0Y40.772 Y
CL, confidence limit.
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1.0000 V
Gabr et al.
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the 14 ureteral complications after LLDN not performed by the urologist, and ureteral complications occurred after at least 1 kidney transplantation was performed by each of the 7 transplant surgeons. The primary limitation of this study is its retrospective design, which exposes the analysis to unknown bias. In addition, the small number of events (ureteral complications) limited the factors that could be assessed with the multivariate analysis. In summary, ureteral complications after LLDN are uncommon. Our study confirmed that the use of a ureteral stent is protective, as has been well demonstrated in randomized controlled trials. The only other factor associated with ureteral complications after LLDN is donor age, with increased donor age being associated with increased incidence of ureteral complications. We were unable to identify any other factors associated with the incidence of ureteral complications.
MATERIALS AND METHODS From our institutional review boardYapproved prospective database, we identified 480 consecutive cases of renal transplantation after hand-assisted LLDN in the period from January 2008 to February 2013. There were no planned open surgical donor nephrectomies done during this period. We selected this period because only after January 2008 were ureteral complications reliably entered into the database prospectively. Cases were subdivided into three time-based tertiles (i.e., first 160 cases, second 160 cases, and third 160 cases), as a surrogate for surgeon and institutional experience. All renal donors were evaluated by a transplant nephrologist and a transplant surgeon. Standard donor evaluation was applied (12), including computed tomography or magnetic resonance imaging with angiographic phase to define the exact renal anatomy. Laparoscopic donor nephrectomy was performed using a hand-assisted approach, with two or three additional laparoscopic ports. The attending
TABLE 2. Bivariate regression analyses (reported above and below median) No. (%) with ureteral Odds complication ratio
Factor (Q or Gmedian)a Donor age (yr) Q43 G43 Donor BMI (kg/m2) Q26.85 G26.85 Total ischemia (min) Q144 G144 Recipient age (yr) Q49 G49 Recipient BMI (kg/m2) Q27.60 G27.60
95% CL
P
1.009 1.009Y1.106 0.0168 15 (6.10) 3 (1.28) 1.099 0.986Y1.225 0.0875 10 (4.26) 7 (2.98)
TABLE 3.
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Multivariate regression analysis
Factor
Odds ratio 95% confidence limit
Increased donor age Increased donor BMI Male recipient No ureteral stent
1.058 1.118 3.463 10.593
1.005Y1.113 0.991Y1.261 0.765Y15.669 3.131Y35.840
P 0.0301 0.0690 0.0994 0.0001
BMI, body mass index.
surgeons included seven transplant (general) surgeons and one urologist, all fellowship trained. Over time, the procedure has become standardized (6), with some minor variations between surgeons with regard to instrumentation and technique of handling the ureter. In all cases, the donated kidney was initially prepared with cold perfusion and packaging as per the United Network for Organ Sharing protocol. Renal transplantation was performed by one of seven transplant surgeons using an extraperitoneal open surgical approach, with vascular anastomoses to the iliac vessels for adult recipients. The surgeon performing the transplant was not necessarily the same performing the LLDN. The method used to establish ureteral anastomosis to the urinary bladder was extravesical ureterocystostomy (modified Lich-Gregoir technique) or intravesical ureterocystostomy (Politano-Leadbetter technique). In no case was the donor ureter anastomosed to the recipient ureter. In a few cases, the ureter was connected to a previously created ileal conduit. Ureteral stents were placed at the discretion of the operating surgeon; stents were placed routinely by the majority of surgeons but selectively by others. Study data collected regarding the renal donor included age, sex, race, type (living related or unrelated), BMI, side of kidney removed (left or right), arterial anatomy, ureteral anatomy, and total ischemia time. This is in addition to the category of surgeon, that is, transplant surgeon versus urologist. Study data collected regarding the recipient included age, sex, race, BMI, history of prior renal transplantation, technique of ureteral anastomosis, use of ureteral stent, serum creatinine on discharge, and need for temporary posttransplant hemodialysis. During the postoperative period, staff regularly reviewed the medical record to ascertain the presence or absence of ureteral complications. All cases in which ureteral complications were reported underwent review by the first author to confirm ureteral leak or ureteral stricture. Owing to their low incidence, we analyzed ureteral complications as a whole, without subgroup analysis for leaks or strictures. To determine the bivariate association of donor and recipient factors with ureteral complications, we used exact logistic regression analysis to take into account the small number of ureteral complication events. For multivariable analysis, we performed backward model building procedure to determine significant clinical predictors for the incidence of ureteral complications. Associations between predictors and the outcome are shown as odds ratios with 95% confidence limits. Statistical analyses were performed using SAS version 9.2 software (SAS Institute, Cary, NC).
1.000 1.000Y1.000 0.5697 11 (4.64) 7 (2.95)
REFERENCES 0.996 0.967Y1.026 0.7696
10 (4.17) 8 (3.43) 1.003 0.944Y1.038 0.7193 8 (3.35) 10 (4.20)
a These values are given for illustration only; the odds ratios, 95% confidence limits (CL), and P values are derived from the analysis of continuous variables. BMI, body mass index.
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