| Abstract|| |
Effects of laparoscopic donor nephrectomy (LDN) on graft function, especially early post-transplant, have been controversial. To assess and compare early and late graft function in kidneys procured by open and laparoscopic methods, a retrospective observational study was carried out on 37 recipients-donors who underwent LDN after introduction of this technique in February 2007 at our center, a tertiary care nephrology referral center. Demographic, immunological and intraoperative variables as well as immunosuppressive protocols and number of human leukocyte antigen (HLA) mismatches were noted. Early graft function was assessed by serum creatinine on Days two, five, seven, 14 and 28 and at the time of discharge. Serum creatinine values at three months and at one year post-transplant were considered as the surrogates of late graft function. Data obtained were compared with the data from 33 randomly selected kidney transplants performed after January 2000 by the same surgical team, in whom open donor nephrectomy was used. Pearson's chi square test, Student's t test and Mann-Whitney U test were used for statistical analysis. Early graft function (serum creatinine on Day five 2.15 mg/dL vs 1.49 mg/dL, P = 0.027) was poorer in the LDN group. Late graft function as assessed by serum creatinine at three months (1.45 mg/dL vs 1.31 mg/dL, P = 0.335) and one year (1.56 mg/dL vs 1.34 mg/dL, P = 0.275) was equivalent in the two groups. Episodes of early acute graft dysfunction due to acute tubular necrosis were significantly higher in the LDN group (37.8% vs 12.1%, Z score 2.457, P = 0.014). Warm ischemia time was significantly prolonged in the LDN group (255 s vs 132.5 s, P = 0.002). LDN is associated with slower recovery of graft function and higher incidence of early acute graft dysfunction due to acute tubular necrosis. Late graft function at one year is however comparable.
|How to cite this article:|
Jamale TE, Hase NK, Iqbal AM. Laparoscopic donor nephrectomy versus open donor nephrectomy: Recipient's perspective. Saudi J Kidney Dis Transpl 2012;23:1175-80
|How to cite this URL:|
Jamale TE, Hase NK, Iqbal AM. Laparoscopic donor nephrectomy versus open donor nephrectomy: Recipient's perspective. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 Apr 7];23:1175-80. Available from: http://www.sjkdt.org/text.asp?2012/23/6/1175/103556
| Introduction|| |
Kidney transplantation has emerged as the most cost-effective definitive treatment for patients with end-stage kidney disease. Increasing the live donor pool is highly desirable given the critical demand-supply issues with deceased donor program. After its introduction in the 1990s', laparoscopic donor nephrectomy (LDN) has gained wide acceptance among the transplant community as evidenced by the fact that, today, more than 50% of the centers in the US have adopted LDN for procuring donor kidney.  Similar trends have been observed in India. This change in the practice is largely driven by the obvious advantages of laparoscopic surgery relevant to donor, i.e. lesser analgesia requirement, early ambulation and reduced duration of hospital stay, ,,,,,, although there is lack of robust data from randomized controlled trials to support this practice.  Effect of LDN on graft function has remained a matter of debate. Some studies have documented poorer graft function, especially early post-transplant after LDN, ,, while others have demonstrated equivalent graft function. ,,,,, The present study compares the effect of these two methods of kidney procurement on graft function in a tertiary care nephrology referral center.
| Subjects and Methods|| |
After its introduction in February 2007 at our center, 37 live donor kidney transplants were performed by this technique over the next two years. Thirty-seven consecutive donor-recipients were studied for demographic, immunologic and clinical characteristics. Thirty-three cases of open donor nephrectomy (ODN) were selected from our transplant data-base operated upon by the same surgical team from January 2001 to December 2006. Computer-generated random numbers were used to select 33 cases out of a total of 79 cases operated during this period.
Donors underwent protocol evaluation for renal function (assessed by creatinine clearance, DTPA renogram and intravenous urography), comorbidities and assessment of renal vessels by computerized tomography or conventional renal angiography. Age, sex, weight, relationship between donor and recipient, number of HLA mismatches and immunosuppression protocol were noted. Hand-assisted LDN using the transperitoneal approach was used for kidney retrieval in the LDN group. Extraction was done by infra-umbilical midline vertical or Pfannenstiel incision. Thirty-four and three kidneys were retrieved from the left and right sides in the LDN group, respectively. In the ODN group, 28 and five kidneys were from the left and right sides, respectively. No conversion to open method was required in the laparoscopic approach. No major vascular or ureteric complications were noted in either of the groups. ODN was done using the standard retroperitoneal approach. Intraoperative variables like warm ischemia time (WIT) and cold ischemia time (CIT) were recorded. The WIT was defined as the time from renal artery occlusion to kidney perfusion. The CIT was defined as the time from kidney perfusion to the start of revascularization.
Immunosuppression protocol included triple immunosuppression involving a calcineurin inhibitor (CNI), either cyclosporine (CSA) or tacrolimus (TAC), antimetabolite (azathioprine or mycophenolate) and prednisolone. Induction with biologic agents such as anti-thymocyte globulin (ATG)/basiliximab/daclizumab was used only for high immunologic risk patients such as spousal transplant, six HLA antigen mismatches. Post-operatively, renal function was assessed by daily estimation of serum creatinine until stabilization of graft function.
Early acute graft dysfunction was defined as 25% rise from baseline in serum creatinine (confirmed on two different occasions) or an absolute increase of 0.3 mg/dL or decrease in urine output below 1 mL/kg/h for more than 3 h occurring within 90 days post-transplant. These patients underwent standard clinical, laboratory and radiographic evaluation (transplant ultrasound and Doppler DTPA renogram, and trough blood levels of CSA/TAC. Assessment for viral nephropathies by polymerase chain reaction was undertaken as clinically indicated and decided by the consultant nephrologist for CMV/BK viruses. Graft biopsy was done as clinically indicated. All the episodes of graft dysfunction were evaluated as per standard protocol involving assessment and correction of hydration, evaluation for CNI toxicity with trough level measurements (target C° level was 200-300 ng/mL for CSA and 8-11 ng/mL for TAC in the first three months post-transplant), ultrasound and Doppler evaluation of the graft. ATG was used as CNI-sparing agent in five cases of graft dysfunction. Suspected/biopsy-proven acute rejection was treated with three to five doses of methylprednisolone 500 mg each.
Late graft function was evaluated by serum creatinine at three months and one year post-transplantation.
Thirty-three recipients/donors of the ODN group were selected by method of computer-generated random numbers operated upon by the same surgical team from January 2001 to January 2007. Data on donor-recipients of the ODN group were obtained on demographics, immunological, intraoperative variables and early and late graft function from transplant database of our center for comparison.
| Statistical Analysis|| |
Data obtained were represented as mean ± 2SD. Pearson's chi square test, Student's t test and Mann-Whitney U test were used for statistical analysis with significance set at a P-value of <0.05. SPSS software version 16 was used for statistical analysis.
| Results|| |
Demographic profile of donor and recipients was similar in the LDN and ODN groups, except for donor's weight, which was higher in the LDN group. Age, sex and proportion of related and unrelated transplants was similar in both groups [Table 1].
Numbers of HLA mismatches and cold ischemia time were also similar in both groups. How ever, patients in LDN group had prolonged WIT [Table 2].
Mean CIT in the LDN and ODN groups was 100.76 min and 110.55 min, respectively, with standard deviation of 34.006 and 134.68 and median of 90 and 88, respectively. Findings were suggestive of skewed observations. Therefore, non-parametric test for comparing two independent groups (Mann-Whitney U test) was applied. CIT was not significantly different. Mean WIT in the LDN and ODN groups was 263.73 s and 209.53 s, respectively, with standard deviation of 255 and 132.5, again suggestive of skewed observations and, therefore, the Mann-Whitney U test was applied for this group as well. WIT was found to be significantly longer in the LDN study group (P = 0.002).
Serum creatinine was significantly lower in the ODN (1.497 mg/dL) group as compared with the LDN group (2.154 mg/dL) on Day 5 (P = 0.027), whereas Day 14 onwards till discharge the mean serum creatinine levels were comparable in both groups. Similarly, late graft function, as evaluated by serum creatinine at three months and one year, was comparable in both groups [Table 3]. Although graft function after two weeks was not statistically different in the two groups, serum creatinine continued to remain higher, a trend that persisted till the end of the follow-up.
Incidence of early acute graft dysfunction was significantly higher in recipients of the LDN group. Acute tubular necrosis (ATN) was observed in 14 (37.8%) out of 37 recipients of LDN and in four (12.1%) out of 33 recipients of ODN [Table 4]. Diagnosis of ATN was confirmed by histopathology in 11 cases and by clinical judgement of the consultant nephrologist in three cases.
When the test of significance between two proportions was applied, this difference was highly significant (P = 0.014). The incidence of acute rejection (AR) was not significantly different in the two groups, three out of 37 and three out of 33 in the LDN and ODN groups, respectively. More recipients in the laparoscopy group required use of anti-thymocyte globulin (7 vs 2). This was not a part of the routine immunosuppression protocol, and this use was necessitated by the higher incidence of ATN in this group when CNI sparing was desirable.
| Discussion|| |
Our findings showed that there was a slower recovery of graft function in the LDN group during the early post-kidney transplant period as evidenced by significantly higher serum creatinine on the 5 th post-operative day. Serum creatinine on the 2 nd , 7 th and 14 th days and at discharge also remained higher in recipients of the LDN group, although this difference was not statistically significant. These findings are consistent with observations of several other investigators, ,, who have reported slower decline in serum creatinine and higher creatinine levels in the first week following transplant and at the time of discharge. On the other hand, many reported equivalent graft function in recipients of both the groups.
What might be the causes of these findings?
First, part of this may be related to variation in the study designs and methods used to assess graft function. Studies comparing laparoscopic and ODN have concentrated mainly on the surgical end points as the primary outcome measure. Graft function was assessed as secondary outcome by relatively insensitive methods like presence or absence of delayed graft function (DGF), i.e. requirement of dialysis within one week of transplant or serum creatinine >2.5 mg/dL on Day five post-transplantation, ,,, End points like DGF requiring dialysis and graft loss are rare outcomes in today's era of kidney transplantation and, therefore, studies utilizing these end points can miss a large proportion of recipients who develop clinically significant graft dysfunction. This leads to underestimation of the incidence of subtle but still significant graft dysfunction post-transplant. We assessed graft function as the primary outcome assessed by using smaller increases in serum creatinine as the marker of poor graft function rather than using parameters such as DGF or primary non-function. This enabled us to diagnose graft function more accurately.
Second, in many studies, prolonged WIT has been a consistent observation in laparoscopic donor nephrectomy, , and our data is consistent with this. This could be one the explanations of the higher incidence of ATN and poorer early graft function in our patients.
Third, factors intrinsic to the technique of laparoscopy may have contributed to our findings. The adverse effect of CO 2 pneumoperitoneum on renal hemodynamics has been demonstrated in both animal and human subjects who underwent laparoscopic gastric bypass surgery. , Laparoscopic nephrectomy may also involve more intraoperative handling of the kidney, which can increase the risk of renal vessel spasm and trauma to the kidney while challenging the extraction step. 
To assess the effect of WIT, we subdivided recipients according to the duration of WIT into two subgroups; those with WIT above 4 min (n = 19) and others with below 4 min (n = 18). There was no significant difference in these two groups as regards early graft function (serum creatinine 2.09 vs 2.21; P = 0.831), suggesting that the other factors discussed above (pneumoperitoneum, graft handling, etc.) might have played a role. Recipients in the LDN group were also analyzed for graft function after dividing them into three groups: first 12, second 12 and last 13, to identify the "learning curve effect," if any. These three groups had comparable graft function, pointing against the major role of learning curve issues.
What is the significance of this early acute graft dysfunction when one year outcome is apparently comparable?
Although the long-term impact of early acute graft dysfunction has been a matter of controversy, some studies have reported 20% decline in one year graft survival. ATN may pre-dispose to "silent rejections," which has been postulated to be the main reason for adverse long-term outcome.  Number of episodes of ATN is considered as one of the important etiological factors for development of chronic allograft nephropathy,  which is the major threat to long-term graft survival today. Although long-term graft function was comparable in both groups, as assessed by serum creatinine at three months and one year, we will like to have long-term follow-up of our patients to observe the effect, if any, of early suboptimal graft function on long-term outcome.
Thus, our results raise an important question about the safety of LDN when one evaluates it from the recipient's perspective. Retrospective nature and small patient number are the limitations of our study; however, it emphasizes the need of evidence from prospective controlled studies to assure safety of LDN before it becomes standard practice in kidney transplantation.
| Acknowledgment|| |
The authors would like to thank Mr. Kishor Vardhan and Mr. Ramesh More for their technical assistance.
| References|| |
|1.||Davis CL, Delmonico FL. Living-donor kidney transplantation: A review of the current practices for the live donor. J Am Soc Nephrol 2005;16:2098. |
|2.||Jacobs SC, Cho E, Foster C, Liao P, Bartlett ST. Laparoscopic donor nephrectomy: The University of Maryland 6-year experience. J Urol 2004;171:47-51. |
|3.||Wolf JS Jr, Merion RM, Leichtman AB, et al. Randomized controlled trial of hand-assisted laparoscopic versus open surgical live donor nephrectomy. Transplantation 2001;72:284-90. |
|4.||Nanidis TG, Antcliffe D, Kokkinos C, et al. Laparoscopic Versus Open Live Donor Nephrectomy in Renal Transplantation: A Meta-Analysis. Ann Surg 2008;247:58-70. |
|5.||Bargman S, Feldman LS, Anidjar M, et al. "First, do no harm" monitoring outcomes during the transition from open to laparoscopic live donor nephrectomy in a Canadian centre. Can J Surg 2008;51:103-10 |
|6.||Jacobs SC, Cho E, Dunkin BJ, et al. Laparoscopic live donor nephrectomy: The University of Maryland 3-year experience. J Urol 2000; 164:1494-9. |
|7.||Perry KT, Freedland SJ, Hu JC, et al. Quality of life, pain and return to normal activities following laparoscopic donor nephrectomy versus open mini-incision donor nephrectomy. J Urol 2003;169:2018-21. |
|8.||Andersen MH, Mathisen L, Oyen O, et al. Postoperative pain and convalescence in living kidney donors-laparoscopic versus open donor nephrectomy: A randomized study. Am J Transplant 2006;6:1438-43. |
|9.||Handschin AE, Weber M, Demartines N, Clavien PA. Laparoscopic donor nephrectomy. Br J Surg 2003;90:1323-32. |
|10.||Troppmann C, Ormond DB, Perez RV. Laparoscopic (vs open) live donor nephrectomy: A UNOS database analysis of early graft function and survival. Am J Transplant 2003;3:1295-301. |
|11.||Nogueira JM, Cangro CB, Fink JC, et al. A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy. Transplantation 1999;67:722-8. |
|12.||Troppmann C, McBride MA, Baker TJ, Perez RV. Laparoscopic live donor nephrectomy: A risk factor for delayed function and rejection in pediatric kidney recipients? A UNOS analysis. Am J Transplant 2005;5:175-82. |
|13.||Kok NF, Lind MY, Hansson BM, et al. Comparison of laparoscopic and mini incision open donor nephrectomy: Single blind, rando-mised controlled clinical trial. BMJ 2006;333: 221. |
|14.||Nicholson ML, Kaushik M, Lewis GR, et al. Randomised clinical trial of laparoscopic versus open donor nephrectomy. Br J Surg 2010;97:21-8. |
|15.||Abreu SC, Goldfarb DA, Derweesh I, et al. Factors related to delayed graft function after laparoscopic live donor nephrectomy. J Urol 2004;171:52-7. |
|16.||Derweesh IH, Goldfarb DA, Abreu SC, et al. Laparoscopic live donor nephrectomy has equivalent early and late renal function outcomes compared with open donor nephrectomy. Urology 2005;65:862-6. |
|17.||Greco F, Hamza A, Wagner S, et al. Hand assisted laparoscopic living donor nephrectomy versus open surgey: Evaluation of surgical trauma and late graft function in 82 patients. Transplant Proc 2009;41:4039-43. |
|18.||Honda MR, Hanza A, Greco F, Wagner S, Fischer K, Fornara P. Early and late graft function after laparoscopic hand-assisted donor nephrectomy for living kidney transplantation: comparison with open donor nephrectomy. Urol Int 2010;84:61-6. |
|19.||Tooher RL, Rao MM, Scott DF, et al. A systematic review of laparoscopic live-donor nephrectomy. Transplantation 2004;78:404-14. |
|20.||McDougall EM, Monk TG, Wolf JS Jr. The effect of prolonged pneumoperitoneum on renal function in an animal model. J Am Coll Surg 1996;182:317-28. |
|21.||Chiu AW, Chang LS, Birkett DH, Babayan RK. The impact of pneumoperitoneum, pneumoretroperitoneum, and gasless laparoscopy on the systemic and renal hemodynamics. J Am Coll Surg 1995;181:397-406. |
|22.||Sahadevan M, Kasise B. Long term post transplant management and complications. In, Danovitch GM, ed. Handbook of Kidney Transplantation, 5 th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 19106 USA. 2010. p. 244-5. |
Tukaram E Jamale
Department of Nephrology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 12
[Table 1], [Table 2], [Table 3], [Table 4]