There is worldwide an increasing use of living kidney donors in renal transplantation (1). In Norway, living donors account for almost 40% of all renal transplantations (2). The kidney has conventionally been removed by open technique through a flank incision (in some centers including rib resection). Thus, open nephrectomy has been considered a major trauma for living kidney donors, causing pain and discomfort in the postoperative period (3). In an effort to remove some of these disincentives, Ratner et al. (4) performed the first laparoscopic live donor nephrectomy in 1995. At our single national center in Norway, open nephrectomy has been the established procedure, but since 1998 laparascopic donor nephrectomy has been performed in selected donors. In 2000, an Australian research group performed a systematic literature review of laparoscopic and open living donor nephrectomy and concluded that the evidence base was inadequate to make recommendations regarding surgical technique (5). On this background, we performed the largest randomized quality of life study so far by assigning 122 donors to laparoscopic or open surgery. The first reports from this study have been published, focusing on donor safety (6) and postoperative pain and convalescence (7). To allow for the donors’ subjective assessment of going through laparoscopic or open donor nephrectomy, we performed a long-term comparison of health status and overall quality of life at 1, 6, and 12 months after surgery. In the present study health status included the donors’ perception of functioning, disability, and well-being related to the following eight concepts: physical functioning, role limitations caused by physical health problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health (8). Overall quality of life was defined as a person’s well-being that stems from satisfaction or dissatisfaction with areas that are important to him or her (9).
MATERIALS AND METHODS
During initial evaluation for donation, consecutive donors were asked to participate in the study by local nephrologists throughout the country. Potential donors fulfilling existing criteria for donation and with a single, left renal artery were considered eligible. A total number of 240 living donor nephrectomies were performed during the inclusion period. Among 118 donors not included in the study, two were laparoscopic donor nephrectomies and 116 were open donor nephrectomies. The reasons for performing open donor nephrectomy in 116 cases were administrative circumstances (only two surgeons performing laparoscopic donor nephrectomy), right side chosen (several arteries on left side, differences in kidney size) and extensive previous abdominal surgery. Obesity was not considered a contraindication. Less than five eligible donors were rejected for other reasons. A total of 122 living kidney donors were randomized at admission to hospital, 1–4 days before the elective procedure. Only one patient opted out and was excluded from the study after having been randomized to open donor nephrectomy. The attitude of the Norwegian population regarding laparoscopic versus open surgery was, and still is, quite balanced, and the donors were informed that there was no hard evidence in favor of either procedure. The donors were randomized in blocks of 20 (in series of twenty patients, ten patients were randomized to one arm, and ten to the other). The study protocol was approved by The Regional Ethics Committee.
The nephrectomies were performed at Rikshospitalet–Radiumhospitalet Medical Centre in Oslo, Norway, from 2001 to 2004. The first 23 laparoscopic donor nephrectomies were completed by conventional technique, using a basket for kidney extraction through a midline infraumbilical incision. The last 39 laparoscopic donor nephrectomies were completed by using a modified, simple hand-assisted technique (10). The open donor nephrectomies were performed by conventional retroperitoneal access through flank incision at the level of costa 11–12, and without rib resection. The length of the skin incision varied from 12 to 18 cm. For a more detailed description of the surgical procedures, the reader is referred to our previous report (6). Two different surgeons performed the laparoscopic nephrectomies, one with extensive and one with moderate laparoscopic experience. The latter was responsible for all the hand-assisted procedures. Six different surgeons, all experienced transplant surgeons, performed the open donor nephrectomies.
Perioperative and Postoperative Analgesia
All donors received anesthesia and postoperative pain management guided by the same standardized protocol. At the start of the donor operation 8 mg of dexamethason was administered intravenously as a single dose, whereas intravenous proparacetemol and ketorolac were started at the end of anesthesia. On the day of surgery and on postoperative day 1 and 2, the donors received proparacetamol 2 g four times a day and ketoralac 30 mg three times a day intravenously and thereafter as oral medication, that is, paracetamol 1 g four times a day and ketoralac 10 mg four times a day. For the first postoperative days, a patient-controlled analgesic pump delivered intravenous opioid pain relief (ketobemidon) in bolus doses of 0.1 mg/kg body weight, each dose trigged by the patient-controlled analgesic pump was discontinued between postoperative days 2–5, where after oral ketorolac was offered.
The primary outcomes were health status and overall quality of life. Questionnaires were completed on admission 1–2 days before surgery (baseline) and were responded to by mail at 1, 6, and 12 months after donation, with a reminder by mail/telephone to nonresponders.
The 36-item Medical Outcomes Study Short Form (SF-36, Norwegian version 1.2) was used to assess whether laparoscopic or open donor nephrectomy impacted on the donors’ health status (11). The SF-36 includes one multi-item scale measuring several health domains: (1) physical functioning (PF), (2) role limitations caused by physical health problems (RP), (3) bodily pain (BP), (4) general health (GH), (5) vitality (VT), (6) social functioning (SF), (7) role limitation caused by emotional problems (RE), and (8) mental health (MH). Scores per dimension range from 0 to 100; higher scores indicate better health status. SF-36 has been translated to several languages, and it has been tested for psychometric properties in several countries, including Norway, with internal consistency (Cronbach’s alpha) ranging from 80 (role emotional) to 0.93 (bodily pain) (12). Also, it has been proven to be an adequate instrument for living kidney donors in previous studies (13, 14).
Overall Quality of Life
The 16-item Quality of life Scale-Norwegian (QOLS-N) measures satisfaction with multiple domains of life. This instrument covers relationships and material well-being, health and functioning, and personal, social, and community commitment. It uses a 1- to 7-point rating scale anchored with the words terrible and delighted. A higher total score indicates higher quality of life (15). Cronbach’s alpha of the QOLS-N is reported at 0.86, with test-retest reliability of 0.83 (16).
At the 12 months, the donors were asked questions regarding their perception of the surgical scar, the donation’s impact on personal finances, and whether the donors would make the same decision to donate again. To measure the donors’ perception of the surgical scar we used a 10-cm horizontal Visual Analog Scale (VAS). Patients were asked to draw a vertical line through a scale anchored on the left-hand side with words signifying a very negative perception, and a very positive perception on the right-hand side. 1, 6, and 12 months after donation the donors were asked to report on the occurrence of significant life events, and hereby were able to report on recipient death or graft failure.
The analyses were based on intention-to-treat. Accordingly, one patient converted from laparoscopic to open surgery was classified in the laparoscopic group. A two-sided alpha of 0.05 and 80% power was used for tests of statistical significant differences between groups. Ten point changes on 0–100 scales for measures of health status, or change of 0.5 standard deviations for population norm-based data, were regarded as clinically significant. A moderate effect expectancy for between-groups differences was set at 0.6. Assuming a dropout rate of 10%, the necessary sample size to detect a 0.6 effect expectancy would be 50 patients in each group. Differences between treatment groups were analyzed using Student’s t test for continuous variables and Fisher’s exact test for categorical data. Long-term analyses of health status and overall quality of life were performed using Repeated Measures Analysis of Variance, and paired t-tests from baseline to 1 and 12 months after surgery. We expected to find a quadratic time trend from baseline to 12 months postdonation, with lowest scores occurring 1 month after surgery. Change scores for the SF-36 subscales and QOLS-N single sum score were calculated as the baseline score minus the postoperative score; a positive change indicating worsening and a negative change indicating improvement. Effect sizes were calculated as the standardized response mean (SRM), which is the mean change score divided by the standard deviation of the change score. A SRM of 0.2–0.5 was considered “small,” 0.5−0.8 “moderate.” and >0.8 “large” (17). We used a 5% level of significance. The SPSS statistical package version 12.0 (SPSS, Chicago, IL) was used for all statistical analyses.
A total of 55 men and 67 women participated in the study. Baseline characteristics were well balanced between the two randomized groups (Table 1). There were minor violations of the analgesic protocol, commonly caused by analgesics administrated orally instead of intravenously. Protocol violations have been described in detail previously (7). Five major postoperative complications, resulting in reoperations, occurred in the laparoscopic group. These were bleeding from a port site (1), a forgotten sponge (1), intestinal perforations (2), and incarceration of the bowel in a port site (1). In the open group, there were no major complications. A complete description has been given previously (6). Analyses of data included 96 complete sets of 122 potential data sets. Donors not answering all follow-ups (13 in the laparoscopic group and 13 in the open group) were similar to the available donors regarding background characteristics, health status, and overall quality of life -scores. Among the dropouts, there were donors withdrawing from the study for personal reasons, donors experiencing poor recipient outcomes and donors having problems with reading or writing the Norwegian language.
Cross-sectional analyses showed that donor baseline SF-36 scores were comparable between surgical groups (Fig. 1). At 1 month, the mean bodily pain score was significantly in favor of the laparoscopic group (P=0.009; Fig. 1). The 6- and 12-month assessments showed no significant differences between groups in SF-36 scores. When we performed an additional analysis of all available data sets and subtracted the reoperated and the one converted donor in the laparoscopic group, we found a significant difference in bodily pain (P=0.032) between groups at 6 months in favor of laparoscopy (n=111). Also, we found a significant difference in social functioning at 12 months (P=0.035) in favor of the laparoscopic group (n=108).
Repeated measures analysis of variance, based on intention-to-treat, indicated significant quadratic time trends for the FS-36 subscales, except for mental health and general health (Fig. 1). For both groups, we found a statistically significant deterioration from baseline to 1 month in all subscales of the SF-36, except for the subscales general health in the laparoscopic group and mental health in the open group (Table 2). Between groups, a significantly greater deterioration in bodily pain scores from baseline to 1 month was observed for donors going through open nephrectomy (P=0.004). The remaining subscales of the SF-36 did not show any significant differences in 1-month change scores between groups. SRM exceeded 80 for five subscales indicating a large effect size. At 12 months, the donor scores in both surgical groups were comparable with baseline scores in most of the SF-36 subscales, except for the subscales role physical and vitality in the laparoscopic group (Table 2). SRM for changes from baseline to 12 months varied between 0 and 55, however, most effect sizes were less than 30, indicating no or irrelevant changes.
Overall Quality of Life
No significant differences between groups were demonstrated at 1, 6, and 12 months in the cross-sectional analyses or in repeated-measures analysis of variance. At 12 months, QOLS-N scores were significantly lower compared to baseline, but the changes did not exceed five points.
There were no significant differences between the groups regarding perception of the surgical scar, the donation’s impact on personal finances or decision-making. Only one donor in each group reported that they would not decide to donate again if possible.
In line with Wolf’s first randomized study (14) and later nonrandomized trials (18–20), our data showed that the donors in the laparoscopic group reported significantly less bodily pain during the first month after donation. This finding remained unchanged when protocol violations and reoperations/conversions were subtracted. When taking patient background characteristics into account, the results also remained unchanged. We also analyzed data from the 26 donors who did not complete all follow-ups, and found that this subgroup did not differ significantly regarding background characteristics. Thus, we suggest that the difference in the bodily pain subscale is caused by surgical technique. In a previous study of patient reported outcome (21) pain was listed as the major obstacle preventing return to work and normal activities. Our finding therefore suggests an important patient-experienced benefit in donors going through laparoscopic surgery. Also, early postoperative pain may increase the risk of a chronic pain syndrome. Kehlet et al. advocate the use of minimal invasive surgery to reduce this risk (22).
Our long-term analysis showed that the 12 months donor-scores for both groups were comparable with baseline scores in most of the SF-36 subscales. Also, our 12 months assessments were similar to those presented in previous donor follow-up studies using SF-36 (13, 23). Although Perry’s retrospective study (20) showed significant differences in SF-36 scores in favor of laparoscopic surgery at 6–12 months after donation, our comparison did not demonstrate any long-term differences between the groups. Our findings are in line with Kok et al. (24), who reported no differences between groups at 3, 6, and 12 months after donation, using SF-36 in their prospective study. In their retrospective study Buell et al. reported similar long-term outcomes, finding no significant differences in the SF-36 scores between laparoscopic and open groups (25). There appears to be both a procedural and institutional learning curve for laparoscopic surgery and we had a high rate of major complications and reoperations in our laparoscopic series. The result of our additional analysis supports this assumption. Also, the fact that both groups at 12 months returned to preoperative levels in most SF-36 subscales and were comparable to those in the general Norwegian population (12), may explain why possible minor long-term differences in quality of life were hard to prove.
The groups were comparable regarding overall quality of life, questions about surgical scar, personal finances, and decision-making. A possible explanation may be that the donors had a positive attitude to their life-situation as a consequence of having donated a kidney, and that this aspect was more essential in their assessments, than were the disincentives as the result of surgery. In line with our results, Perry et al. (20) reported no significant difference between groups regarding cosmetic satisfaction.
This study is to our knowledge the largest randomized quality of life study comparing laparoscopic and open donor surgery. In our single center study, as many as 79% of the randomized donors answered questionnaires at all follow-ups. Nevertheless, some limitations should also be addressed. First, two different laparoscopic techniques were used during the final stages: standard laparoscopy with basket extraction and a modified hand-assisted technique. Taking into account that the infraumbilical incision and extent of dissection were exactly the same with both techniques, we believe that the impact on the donor is equivalent. Earlier reports support this assumption (26, 27). Second, this study was not blinded. Although blinding was attempted in a previous donor study comparing laparoscopic and open donor surgery (28), we believe that it is difficult to fully obscure which surgical method has been used. Besides, blinding is only possible in the immediate postoperative phase before the dressings are removed, being of less importance in long-term assessments. Third, only two surgeons performed the laparoscopic nephrectomies, one with extensive laparoscopic experience and one with less extensive experience, whereas six surgeons performed the open nephrectomies. However, these six were all consultant transplant surgeons very well trained in the common open procedure and committed to the standardized guidelines of a single center.
We conclude that although there was a clinically significant difference between groups in the subscale bodily pain at one month, long-term comparison only revealed significant differences in favor of laparoscopy when adjusting for reoperations/conversions. Both groups reached baseline scores in most SF-36 subscales at 12 months and this may explain why possible minor benefits are hard to prove.
The authors are grateful to Geir Aamodt, Ph.D., for statistical advice and Trond Andrè Aag and Tone Margrethe Sverresborg for data support. The patients generously shared their experiences and made this study possible. This study is funded with the aid of Southern Norway Regional Health Authority, Norwegian Nurses’ Association, The Department of Surgery and The Center of Patient Participation and Nursing Research at Rikshospitalet-Radiumhospitalet Medical Center, Norway.
1. Lumsdaine JA, Forsythe JLR, Lear PA. Living donation (renal). In: Forsythe JLR, ed. Transplantation: A Companion to Specialist Surgical Practice
. Philadelphia: Elsevier Saunders; 2005.
2. Westlie L, Leivestad T, Lien B, Meyer K, Fauchald P. Report from the Norwegian national hospitals living donor registry: One-year data, January 1, 2002. Transplant Proc
2003; 35: 777.
3. Schostak M, Wloch H, Müller M, et al. Living donor nephrectomy in an open technique: A long-term analysis of donor outcome. Transplant Proc
2003; 35: 2096.
4. Ratner LE, Ciseck LJ, Moore RG, et al. Laparoscopic live donor nephrectomy. Transplantation
1995; 60: 1047.
5. Merlin TL, Scott DF, Rao MM, et al. The safety and efficacy of laparoscopic live donor nephrectomy: A systematic review. Transplantation
2000; 70: 1659.
6. Øyen O, Andersen M, Mathisen L, et al. Laparoscopic versus open living-donor nephrectomy: Experiences from a prospective, randomized, single-center study focusing on donor safety. Transplantation
2005; 79: 1236.
7. Andersen MH, Mathisen L, Øyen 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.
8. Ware JE, Sherbourne CD. The MOS 36-item Short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care
1992; 30: 473.
9. Ferrans CE. Development of a quality of life index for patients with cancer. Oncol Nurs Forum
1990; 17: 15.
10. Øyen O, Line PD, Pfeffer P, et al. Laparoscopic living donor nephrectomy: Introduction of simple hand-assisted technique (without hand-port). Transplant Proc
2003; 35: 779.
11. Ware JE Jr, Kosinski M, Gandek B. SF-36 Health Survey: Manual & Interpretation Guide
. Boston: Health Institute; 1993.
12. Loge JH, Kaasa S. Short form 36 (SF-36) health survey: Normative data from the general Norwegian population. Scand J Soc Med
1998; 26: 250.
13. Giessing M, Reuter S, Deger S, et al. Laparoscopic versus open donor nephrectomy in Germany: Impact on donor health-related quality of life and willingness to donate. Transplant Proc
2005; 37: 2011.
14. Wolf JS, Merion RM, Leichtman AB, et al. Randomized controlled trial of hand-assisted laparoscopic versus open surgical live donor nephrectomy. Transplantation
2001; 72: 284.
15. Burckhardt C, Anderson K. The Quality of Life Scale (QOLS): reliability, validity, and utilization. Health Qual Life Outcomes
2003; 1: 60.
16. Wahl A, Burckhardt C, Wiklund I, Hanestad BR. The Norwegian version of the Quality of Life Scale (QOLS-N). Scand J Caring Sci
1998; 12: 215.
17. Cohen J. Statistical Power Analysis for the Behavioural Sciences
, 2nd ed. Hillsdale, NJ: Lawrence Erlbaum; 1988.
18. Sundquist P, Feuk U, Häggman M, Persson AEG, Stridsberg M, Wadström J. Hand-assisted retroperitoneoscopic live donor nephrectomy in comparision to open and laparoscopic procedures: A prospective study on donor morbidity and kidney function. Transplantation
2004; 78: 147.
19. Lennerling A, Blohmé I, Östraat Ö, Lönroth H, Olausson M, Nyberg G. Laparoscopic or open surgery for living donor nephrectomy. Nephrol Dial Transplant
2001; 16: 383.
20. 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. Hiller J, Sroka M, Holochek MJ, Morrison A, Kavoussi LR, Ratner LE. Functional advantages of laparoscopic live-donor nephrectomy compared with conventional open-donor nephrectomy. J Transpl Coord
1997; 7: 134.
22. Kehlet H, Jensen T, Woolf C. Persistent postsurgical pain: Risk factors and prevention. Lancet
2006; 367: 1618.
23. Reimer J, Rensing A, Haasen C, Philipp T, Pietruck F, Franke GH. The impact of living-related kidney transplantation on the donor’s life. Transplantation
2006; 81: 1268.
24. Kok NFM, Alwayn IPJ, Tran KTC, Hop WJC, Weimar W, IJzermans JNM. Psychosocial and Physical impairment after mini-incision open and laparoscopic donor nephrectomy: A prospective study. Transplantation
2006; 82: 1291.
25. Buell JF, Lee L, Martin JE, et al. Laparoscopic donor nephrectomy vs. open live donor nephrectomy: A quality of life and functional study. Clin Transplant
2004; 19: 102.
26. Slakely DP, Wood JC, Hender D, Thomas R, Cheng S. Laparoscopic living donor nephrectomy: Advantages of the hand-assisted method. Transplantation
1999; 68: 581.
27. Wolf JS, Moon TD, Nakada SY. Hand-assisted laparoscopic nephrectomy: comparision to standard laparoscopic nephrectomy. J Urol
1998; 160: 22.
28. Kok NFM, Lind MY, Hansson BME, et al. Comparison of laparoscopic and mini-incision open donor nephrectomy: Single blind, randomised controlled clinical trial. BMJ
2006; 333: 221.