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effects of the 2 different approaches. Subgroup year after transplant, conversion to open donor
analyses (comparing right and left laparoscopic, retro- nephrectomy, donor blood transfusion, donor post-
peritoneoscopic, and hand-assisted nephrectomy) and operative complications, and recipient pos-toperative
sensitivity analyses (including high quality studies and complications; (4) documented operative technique as
only randomized controlled trials) were performed. laparoscopic, hand-assisted, or retroperitoneoscopic;
(5) the articles were published in English or Chinese in
Materials and Methods open access journals; and (6) when multiple trials were
from the same authors and/or institute, only the latest
Study inclusion publication or publication of highest quality was
Medline (PubMed), Embase, Ovid, Cochrane, and included in the study.
Chinese Biomedical Literature databases were
searched for studies performed between 2000 and 2014 exclusion criteria
that compared right and left laparoscopic living-donor Trials were excluded for the following reasons: (1)
nephrectomy. The following medical subject headings case reports, reviews, editorials, abstracts, expert
were used, alone or in combination: laparoscopic, opinions, letters, and noncomparative studies; (2)
nephrectomy, renal transplant, comparative study, live studies reporting on robotic-assisted or 3-dimensional
donor, left, and right. The function of related articles laparoscopic living-donor nephrectomy; (3) studies
was applied to enlarge the search. The references of comparing laparoscopic and open nephrectomy; (4)
each included study were reviewed, and the last study repeated reports from authors, centers, or patient
date for the search was May 2013. To ensure that any populations; or (5) considerable overlap between a
relevant studies were not missed, many laparoscopic cohort evaluated previously.
surgery scholars were consulted. This analysis only
included comparative clinical full-text studies, and Outcomes of interest and definitions
the final articles included in the study were agreed The following outcomes were used to compare right
upon by all authors of this study. and left laparoscopic living-donor nephrectomy: (1)
donor operative parameters operative time (min),
Data extraction operative blood loss (mL), and warm ischemia time
The following data were independently extracted (min); (2) donor postoperative parameter length of
from each study by 2 coauthors (PZ and KW): year of hospital stay (d); (3) donor intraoperative com-
publication, first author, characteristics of targeted plications bowel, liver, spleen, pleural, or lung injuries;
population, research design, interventions, and (4) donor postoperative complications pulmonary,
outcomes of interest. To avoid missing related study vascular, or urologic complications, wound infections,
data, the 2 coauthors attempted to contact study incisional hernias, chronic wound pain, and mortality;
authors when information was lacking or unclear. (5) recipient postoperative complications ureteral leak,
Conflicts between investigators about the outcomes ureteral stricture, and vascular complications; (6)
of interest were reviewed and agreements were conversion to open donor nephrectomy and donor
reached on the final interpretation of the data. blood transfusion; and (7) graft parameters delayed
graft function, 1-year graft loss, and recipient
Inclusion criteria creatinine levels (mg/dL) at 7 days, 1 month, and 1
Studies included in the analysis fulfilled the year after transplant.
following criteria: (1) comparison of right versus left
laparoscopic living-donor nephrectomy in patients Statistical analyses
undergoing living-donor nephrectomy; (2) human This meta-analysis followed the Quality of Reporting
studies, and donors studied had no differences in of Meta-Analyses guidelines and recommendations of
bilateral renal function; (3) inclusion of ≥ 3 of the the Cochrane Collaboration14,15 and was performed
following outcome measures: operative time, with statistical software (Review Manager, Version 5.0,
operative blood loss, warm ischemia time, donor Clicktime, San Francisco, CA, USA) (Stat Manager,
intraoperative complications, hospital stay, delayed V4.1, Stata Corp, College Station, TX, USA). The
graft function, recipient 1-year graft loss, recipient weighted mean difference was used to analyze
creatinine level (mg/dL) at 7 days, 1 month, and 1 continuous variables, and dichotomous variables
216 Kun Wang et al/Experimental and Clinical Transplantation (2015) 3: 214-226 Exp Clin Transplant
were analyzed by determination of odds ratio (OR).16 The Higgins chi-square test was performed to
There were 15 studies identified within 95% evaluate heterogeneity. Statistical heterogeneity was
confidence interval (CI). The OR represented the evaluated by P and I² values. If I² < 50% and P > .1,
occurrence odds of an event in the right compared the heterogeneity was considered to be within an
with left group, and the numerical differences appropriate range and data were pooled using a
between the 2 groups were summarized by weighted fixed-effects model. When significant heterogeneity
mean difference for continuous variables. When was present (I² > 50%; P < .1), the random-effects
P < .05 and 95% CI did not include the value 1, the model was applied. We performed subgroup
OR and weighted mean difference were considered analyses to interpret significant heterogeneity. To
statistically significant. When continuous data were further investigate heterogeneity, Galbraith plots
presented as range and mean, we used statistical analysis was performed to identify the outliers which
algorithms and bootstrap resampling techniques to might have contributed to the heterogeneity. The
calculate and verify the standard deviations (SD). effect of the low-quality studies on the overall effect
To evaluate the quality of the studies, we used the was detected using sensitivity analysis. We performed
Newcastle-Ottawa Scale, with minimal modifications Egger tests and Begg funnel plots to evaluate
matched for the requirements of the present study publication bias of studies in all comparison models.
(Table 1).17 The quality of the studies was assessed
according to the following criteria: patient selection, Results
comparability between the 2 groups, and outcome
assessment. Except for the only randomized controlled eligible studies
trial, each study was assessed by scoring from 0 to 9 The identified studies selected for this analysis
stars. The maximum number of stars in the selection, successfully matched the selection criteria and had
comparability, and outcome categories was 3, 4, and 2. been published between 2000 and 2014. The search
The studies that had ≥ 5 stars and the only randomized strategy generated 105 relevant clinical studies,
controlled trial were believed to be of high quality. including 19 full text articles that were further
Table 1. Quality Assessment of Nonrandomized Studies
Selection Comparability Outcome Assessment Total
1 2 3 4 5 6 7
Hoda 2011 ☆ ☆ ☆ ☆ ☆ 5
Tsoulfas 2012 ☆ ☆ ☆ ☆ 4
Diner 2006 ☆ ☆ ☆ 3
Omoto 2013 ☆ ☆ ☆ ☆ ☆ 5
Gures 2013 ☆ ☆ ☆ ☆ ☆ 5
Maartense 2004 ☆ ☆ ☆ 3
Posselt 2004 ☆ ☆ ☆ ☆ 4
Dol 2008 ☆ ☆ ☆ ☆ ☆ 5
Ko 2008 ☆ ☆ ☆ ☆ 4
Bachir 2011 ☆ ☆ ☆ ☆ 4
Husted 2005 ☆ ☆ ☆ ☆ ☆ 5
Ruszat 2007 ☆ ☆ ☆ ☆ 4
Hoda 2010 ☆ ☆ ☆ ☆ ☆ 5
Narita 2006 ☆ ☆ ☆ ☆ 4
investigated. Of these, 4 studies were excluded: the Figure 2. Meta-Analysis of Right Versus Left Laparoscopic Living-Donor
Nephrectomy
data of 2 studies were incomplete, containing only
averages; 1 study did not contain a control group;
and the data of 1 study were unclear. Therefore, 15
studies were identified for inclusion, including 1
randomized controlled trial 18 and 14 nonrandomized
comparative studies. A flow diagram outlined the
process of study selection (Figure 1).
Figure 1. Flow Diagram Outlining the Study Selection Process
Study characteristics
The characteristics of 15 studies that fulfilled the
inclusion criteria were summarized (Table 2).
Analysis was performed on 3073 patients; 2420
patients (78%) had undergone left laparoscopic
living-donor nephrectomy and 653 patients (22%)
had undergone right laparoscopic living-donor
nephrectomy. There were 6 studies that recorded
hand-assisted laparoscopic living-donor neph-
rectomy (total, 630 patients). There were 7 studies
that recorded traditional laparoscopic living-donor
nephrectomy (total, 1792 patients). There were 2
studies that recorded retroperitoneoscopic living-
donor nephrectomy (total, 651 patients). Conversion to
open surgery was reported in 44 cases (1.4%) in 8
studies. There were 17 patients (0.6%) who needed
donor blood transfusion in 8 studies. Data collection
218 Kun Wang et al/Experimental and Clinical Transplantation (2015) 3: 214-226 Exp Clin Transplant
Abbreviations: NA, not available; OR, odds ratio; RCG, retrospective control group; RCT, randomized controlled trial
*Dichotomous variables are presented as odds ratios.
was prospective in 1 study, and the other studies were intraoperative complication rate between the 2
retrospective. There was 1 randomized controlled trial groups (OR, 0.53; 95% CI, 0.31 to 0.92; P = .03); the
and the other studies were nonrandomized. left group had a higher rate of donor intraoperative
complications. The intraoperative complications
Meta-analysis of right versus left laparoscopic included bowel or liver injury, spleen or pancreas
living-donor nephrectomy injury, pleural or lung injury, and intraoperative
For the donors, operative time was shorter in the bleeding. However, there was no difference between
right than left group by 13.44 minutes (95% CI, -22.73 groups for rate of conversion to open donor
to -4.15 min; P = .005) (Table 3 and Figure 2). nephrectomy (OR, 0.54; 95% CI, 0.24 to 1.21; P = .14).
Operative blood loss was lower in the right than There was no significant difference between the 2
left group by 10.53 mL (95% CI, -17.43 to -3.64 mL; groups in donor postoperative complication rate
P = .003). Comparison of warm ischemia time (OR, 1.03; 95% CI, 0.68 to 1.56; P = .88). Donor
between the right and left group showed no postoperative complications included pulmonary,
significant difference (95% CI, -0.09 to 0.26 min; vascular, and urologic complications, wound
P = .33). There was a difference in the donor infection, incisional hernia, and chronic wound pain.
Kun Wang et al/Experimental and Clinical Transplantation (2015) 3: 214-226 219
The point estimates of the odds ratio and weighted mean difference were considered statistically significant at the level of P < .05 if the 95%
confidence interval did not include the value 1.
If I² < 50% and P > .1, it may be considered to indicate nonsignificant heterogeneity.
Patients undergoing right or left laparoscopic living- The operative blood loss was similar (right, 21.4 mL;
donor nephrectomy had similar postoperative left, 6.7 mL; 95% CI, -33.26 mL to 13.49 mL; P = .41)
recovery. There were no significant differences and the rate of donor intraoperative complications
between the 2 groups regarding donor hospital stay was similar (right, 27.9%; left, 18.5%; 95% CI, 0.23%
(weighted mean difference, -0.06 d; 95% CI, -0.16 d to 1.46%; P = .25) between the 2 groups. Recipient
to 0.05 d; P = .32). serum creatinine at 7 days after surgery was not
compared between the 2 groups because it was
Recipient parameters included only in 1 study.
Pooled analysis of 7 studies showed that there was
no significant difference between the right and left Right versus left living-donor nephrectomy
group (95% CI, 0.70% to 1.41%; v = .97) in rate of This comparison revealed similar results as in the
overall recipient postoperative complications such as original analysis (Figure 4). There was a difference in
ureteral leak, ureteral stricture, or vascular com- the rate of donor conversion to open living-donor
plications. Analysis of 9 studies suggested that nephrectomy between the 2 groups (right, 41.9%; left,
patients in the right and left groups had similar 36.8%; 95% CI, 0.11% to 0.97%; P = .04). There was no
recipient delayed graft function (95% CI, 0.39% to difference in the rate of donor blood transfusion
1.76%; P = .63). There was no significant difference in between right and left transperitoneal laparoscopic
the rate of recipient 1-year graft loss (95% CI, 0.71% living-donor nephrectomy (95% CI, 0.06% to 1.79%;
to 3.00%; P = .3) from the analysis of 11 studies. Both P = .20).
groups had similar graft function assessed at 7 days,
1 month, and 1 year using serum creatinine Right versus left retroperitoneoscopic nephrectomy
levels (mg/dL) (7 d: 95% CI, -0.05 to 0.09; P = .54) There was no significant change in the results for
(1 mo: 95% CI, -0.16 to 0.06, P = .35) (1 y: 95% CI, most outcomes from the original analysis (Figure 5).
-0.11 to 0.16, P = .73). Overall, meta-analysis of However, compared with the original analysis, there
related data showed no significant differences were no differences in operative time (95% CI, -16.33
between the right and left groups in recipient relative min to 12.04 min; P = .77) and operative blood loss
parameters. (95% CI, -13.54 mL to 29.11 mL; P = .47).
Abbreviations: MD, mean difference; SE, effect estimate versus effect estimate for each study under the outcome
Studies are marked by a dot and 95% confidence intervals by lines.
operative blood loss of 10.53 mL compared with the right laparoscopic nephrectomy demonstrated no
left group. In 1 study, the ranges for operative blood difference in terms of donor hospital stay. In the
loss were significantly wider (left, 10 to 1000 mL; analysis of follow-up data, no significant differences
right, 25 to 1200 mL); this might relate to the in postoperative measures of graft function between
unpredictability and uncertainty of the operative the left and right groups were evident such as
process. The 10.53 mL difference in donor blood loss postoperative recipient serum creatinine at 7 days, 1
and 13.44 min difference in operative time were month, or 1 year. Some studies showed that serum
statistically significant but most likely were not creatinine was useful in detecting minor degrees of
clinically relevant. Therefore, we do not need to deterioration of renal function, and glomerular
further study the origin of the subtle differences in filtration rate may be estimated accurately based on
the operation. In our study, there were no obvious serum creatinine according to the Kidney Disease
differences regarding donor or recipient overall Improving Global Outcomes and National Kidney
postoperative complications. However, the outcomes Foundation/Kidney Disease Outcomes Quality
showed that the left group had a higher rate of donor Initiative guidelines.26,27 Nevertheless, as a more
total intraoperative complications than the right intuitive indicator, the rate of 1-year graft loss should
group (OR, 0.53; P = .03). The donor intraoperative be evaluated. In our meta-analysis, the rates of 1-year
complications included bowel or liver injury, spleen or graft loss on the right and left sides were 2.6% and
pancreas injury, pleural or lung injury, and vascular 2%, and we found no statistical significance in the
injury. The more complex anatomic structures comparison of the rate of 1-year graft loss.
surrounding the left kidney might contribute to The sensitivity analyses were conducted after
the higher rate of overall donor intraoperative excluding the low-quality trials from the non-
complications. Although conversion to open technique randomized controlled trials. We compared the effect
was not desired, it sometimes was inevitable. The on the results of the overall analyses. The results of
intraoperative complications were the chief causes sensitivity analyses were consistent with the results of
of conversion to open donor nephrectomy.20 the overall analysis; no significant differences
Nevertheless, our study showed no significant were revealed in all indicators from the overall
differences in the rate of conversion to open donor results. This increases the credibility of our overall
nephrectomy or donor blood transfusion between the analysis.
2 groups; the higher incidence of intraoperative Heterogeneity analysis of the right and left
complications on the left side did not lead to a higher laparoscopic living-donor nephrectomy suggested
incidence of open conversion. Thus, intraoperative significant heterogeneity in operative time, warm
complications on the left side were not severe, and ischemia time, and postoperative recipient serum
urologists may provide nonoperative treatment. We creatinine at 1 year. To explore the sources of
considered that the more complex anatomic structures heterogeneity, we performed subgroup analyses
surrounding the left kidney may cause some but not according to the specific operative method. In hand-
serious intraoperative effects on the operation because assisted nephrectomy, the heterogeneity of 3 models
the longer renal vein of the left side may make the decreased significantly, but in the other 2 subgroups,
implant procedure less demanding and may reduce heterogeneity did not decrease. Therefore, the
the difficulty of the operation.21-23 Therefore, in our specific operative method was not the main source
analysis, the right side did not have an advantage of heterogeneity. To further investigate the hetero-
regarding the rate of overall donor intraoperative geneity, we performed Galbraith plot analysis to
complications compared with the left side. identify the outliers that might have contributed to
For urologists, early recovery of graft function is the heterogeneity. Our results showed that the
most concerning.24 Our study showed no differences studies of Posselt and associates and Dols and
in the warm ischemia time. A related survey by coworkers were outliers in operative time. All I²
Abreu and coworkers25 reported that warm ischemia values decreased and P was > .10 after excluding
time plays an important role in delayed graft these studies in the operative time model. Galbraith
function. In our analysis, the rate of delayed graft plot analysis showed that the studies by Dols and
function was similar in the right and left groups associates and Maartense and coworkers were
(right, 3.2%; left, 4.1%). Studies comparing left versus outliers in warm ischemia time. The I² value
Kun Wang et al/Experimental and Clinical Transplantation (2015) 3: 214-226 225
decreased < original value and P was > original value and all dichotomous outcomes examined in this
after excluding the studies of Dols and coworkers analysis.
and Maartense and associates. In the model for Limitations of the present study included the
postoperative recipient serum creatinine at 1 year, differences in the number of patients between the 2
because the number of studies included was not groups. Many urologists prefer the left than right
sufficient, we could not identify the outliers that side due to the bias of the less demanding operation
might have contributed to the heterogeneity. The from the longer renal vein, and they conclude by
results indicated that these studies might be the intuition that the less demanding operation may
major source of heterogeneity for operative time and improve the effect of the operation. Therefore,
warm ischemia time. the number of cases was less in the right than left
Many studies were affected by factors such as group. More trials of the right procedure are required
patient preference and could not randomly assign the for a more comprehensive comparison of the
operative approach. Therefore, nonrandomized 2 sides.
controlled trials accounted for a high proportion in In our study, right laparoscopic living-donor
our analysis, which is a possible criticism that the nephrectomy might be associated with shorter
meta-analysis may reinforce inherent systematic operative time, lower operative blood loss, and fewer
biases of the studies, cause spurious statistical stability, donor intraoperative complications. We considered
and discourage further research. However, Deeks and that several modifications used for right donor
coworkers28 have assessed nonrandomized controlled nephrectomy and recipients played an important role
trials by using resampling techniques; they showed in improving the safety and efficacy of right lapa-
that results of randomized and nonrandomized roscopic living-donor nephrectomy by prolonging the
studies may differ, but similarities and differences vein length with inverted kidney transplant,30 the use
may be explained by other confounding factors. of hand-assisted devices, and use of a modified
Therefore, we believe that meta-analysis of nonran- Satinsky atraumatic vascular clamp.31 However,
domized studies may be useful when randomized compared with left laparoscopic living-donor
controlled trials are not available. Nevertheless, nephrectomy, the modifications did not decrease the
further prospective randomized trials are required for operative difficulty significantly and made the
a more comprehensive comparison of the 2 sides. operation less demanding for the urologists.
In several studies, ranges but not standard In summary, right laparoscopic living-donor
deviations were recorded. Some workers doubt that nephrectomy did not have significant clinical
this may lead to publication bias. However, a recent advantages. Moreover, there were no differences
study by Hozo and coworkers29 provided a rigorous between left and right laparoscopic living-donor
scientific method to estimate the standard deviation. nephrectomy in most important outcomes. Our
Using these formulas, they suggested that we can meta-analysis statistically confirmed that right and
“use clinical trials even when not all of the left laparoscopic living-donor nephrectomy were
information is available and/or reported.” In similar in the effects of surgery and postoperative
addition, in our meta-analysis, studies that recorded graft function. Therefore, when there are no
ranges rather than the standard deviation only differences in bilateral renal function, surgeons may
accounted for a small proportion. The results of take the right or left kidney randomly from the
Egger test did not suggest any evidence of perspective of intraoperative and postoperative
publication bias in the overall outcomes. effects. However, we recommend using the left
In some studies, there was slight variability in kidney because the longer renal vein of the left
terms of definitions, inclusion criteria, and mea- kidney may reduce operative difficulty in taking the
surement of outcomes. This variability might donor kidney and may make the operation less
introduce bias into the current study. However, demanding for urologists.
consensus in definitions, inclusion criteria, and
measurement of outcomes was reached between References
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