Abstract
Background/Aim: With the increasing use of marginal donors, it is important to identify factors for outcomes in kidney transplantation. The aim of the present study was to evaluate the influence of surgical complications for graft survival after kidney transplantation and identify risk factors for surgical complications. Patients and Methods: We performed a retrospective cohort study by chart review of patients who underwent kidney transplantation at the Taichung Veterans General Hospital in the period from 2007 to 2018. Results: Of the 433 patients who underwent kidney transplantation, 57 experienced surgical complications with an occurrence rate of 13.2%. The most common complications were vascular complications (n=31; 7.2%), followed by urologic (n=9; 2%) and wound (n=9; 2%) complications. From univariate analyses, risk factors for surgical complications were cold ischemia time, blood loss, operation time, number of vascular anastomoses and year of operation. From univariate and multivariate analyses, operation time was associated to surgical complications. Patients with surgical complications experienced worse both one-year and five-year death-censored graft and patient survival. Conclusion: Surgical complications were associated with higher risk of death-censored graft failure and mortality. Cold ischemia time, blood loss, operation time, number of vascular anastomoses and year of operation were risk factors for surgical complications. Efforts should aim to minimize surgical complications to improve both graft and patient survival.
Kidney transplantation is the treatment of choice for patients with end stage renal disease (ESRD) offering improvement in quality of life and survival advantages compared to long-term dialysis (1). The advances of immunosuppressant regimes, antibiotics therapy and surgical techniques improved graft outcomes significantly in recent decades. Nevertheless, as the shortage of organ donation persists, there is a trend toward using high risk donors. It is therefore important to identify risk factors for graft outcomes after kidney transplantation.
Several factors affecting graft survival after kidney transplantation have been reported in the recent literature (2-8). Pre-operative factors include age, sex, body mass index (BMI), deceased donor, human leukocyte antigen (HLA) matching and donor renal function. Transplantation and post-operative factors include cold or warm ischemia time, acute rejection episodes and delayed recovery of graft function. However, studies are scarce regarding surgical factors influencing graft survival. The purpose of the present study is to investigate surgical complications of kidney transplantation and evaluate their impact on outcomes after transplantation.
Patients and Methods
We performed a retrospective cohort study at the Taichung Veterans General Hospital. We included patients who had received kidney transplantation during the period from 2007 to 2018. All relevant clinical and laboratory data were retrieved from the database of Taichung Veterans General Hospital. Their demographics and characteristics were recorded from the time of admission to the date of graft failure or death. The primary endpoint was the occurrence of surgical complications within 3 months after kidney transplantation. Another endpoint was death censored graft loss or death. We excluded patients with incomplete data or lost in follow-up.
Surgical complications were defined as morbidity requiring surgical intervention or percutaneous drainage within 3 months after kidney transplantation. Re-operation was defined as operative morbidity requiring surgical intervention during hospitalization after transplantation. Patients who still required dialysis one week after kidney transplantation were regarded as having delayed graft function. Panel-reactive antibody (PRA) test positive was defined as RPA >10%.
Continuous variables were expressed as mean and standard deviation (SD), and categorical variables were presented frequency. Means of continuous variables were compared between groups using the Mann-Whitney U-test. Similarly, categorical variables were compared using the Pearson’s Chi-square test. Cox regression models with both univariate and multivariate analyses were used to determine predictors for graft survival. The SPSS software (version 19.0; SPSS Inc., Chicago, IL, USA) was used for all analyses. Statistical significance was set at p≤0.05.
This study was approved by the institutional review board (IRB) of Taichung Veterans General Hospital (IRB number: CE:22438A). All the participants provided written informed consent to have data from their medical records for this study. The operation was performed in accordance with national regulations and the Helsinki Declaration.
Results
A total of 433 patients who underwent kidney transplantation at our hospital were analyzed. The mean follow-up duration was 97.4 months. The overall one-year and five-year graft survival rates were 96% and 87.5%, respectively. The mean recipient age was 44.7±13.2 years, with more male patients (54.5%). Patients with surgical complications were associated with more blood loss (208.4 ml for surgical complications, and 205.9 ml for no surgical complications, p=0.002), longer operation time (4.7 hours for surgical complications, and 4.1 hours for no surgical complications, p=0.001), more positive PRA II test (17.5% for surgical complications, and 6.9% for no surgical complications, p=0.001), and had more delayed graft function (35.1% for surgical complications, and 16.1% for no surgical complications, p=0.001). Table I shows the patients’ demographics and characteristics.
Baseline characteristics for kidney transplantation patients with or without surgical complications.
Of the 433 patients undergoing transplantation, 57 (13.2%) experienced surgical complications. Vascular complications occurred most frequently with an incidence rate of 7.2% (n=31). Both urologic complications and wound complications were 2% (n=9). Table II is a summary of these surgical complications.
Summary of surgical complications and management in kidney transplantation.
Univariate analyses revealed that surgical complications were associated with the followings: cold ischemia time [hazard ratio (HR)=1.044, 95% confidence interval (CI)=1.013-1.098, p=0.01], blood loss (HR=1.001, 95% CI=1-1.001, p=0.006), operation time (HR=1.443, 95% CI=1.136-1.833, p=0.003), number of vascular anastomoses (HR=1.655, 95% CI=1.015-2.697, p=0.043) and year of operation (HR=1.081, 95% CI=1.012-1.155, p=0.021). Multivariate analyses showed that surgical complications were related to operation time (HR=1.39, 95% CI=1.057-1.826, p=0.018). Table III showed risk factors associated with surgical complications.
Univariate and multivariate analysis of risk factors for surgical complications in kidney transplantation patients.
Based on univariate analysis, surgical complication was a predictive factor for one-year death-censored graft failure (HR=8.032, 95% CI=2.699-23.903, p<0.001) and death (HR=24.087, 95% CI=5.003-115.974, p<0.001), as well as long-term death-censored graft failure (HR=2.221, 95% CI=1.235-3.994, p=0.008) and death (HR=2.603, 95% CI=1.328-5.105, p=0.005). Multivariate analysis showed that surgical complications were associated with one-year death-censored graft failure (HR=7.242, 95% CI=2.354-22.276, p=0.001) and death (HR=23.719, 95% CI=4.626-121.626, p<0.001), and long-term death-censored graft failure (HR=2.116, 95% CI=1.168-3.835, p=0.013) and death (HR=2.25, 95% CI=1.132-4.475, p<0.021). Results of these analyses were presented in Table IV.
Univariate and Multivariate Cox regression model for outcomes using surgical complications as risk factors in kidney transplantation patients.
Survival curves for patients experiencing surgical complications were shown in Figure 1. Patients with surgical complications had poorer five-year death-censored graft survival (complications 77.7% vs. no complications 92.1%, p=0.006) and survival (complications 81.7% vs. no complications 95.3%, p=0.004) compared to patients without surgical complications.
Survival curves for death-censored graft survival (A) and patient survival (B) between patients with or without surgical complications after kidney transplantation.
Discussion
In the present study, we retrospectively reviewed data of patients undergoing kidney transplantation at the Taichung Veteran General Hospital during the last decade. Basic characteristics and factors affecting surgical complications were evaluated. Based on univariate analyses, factors associated with surgical complications were the following: cold ischemia time, blood loss, operation time, number of vascular anastomoses, and year of operation. Based on multivariate analyses, factor significantly influencing the surgical complications was operation time. Surgical complication was an independent factor for long-term death-censored graft loss and mortality.
According to previous reports, the incidence rate of surgical complications is between 4% and 38% (9-13). The incidence rate is consistent with our study, in which 57 patients (13.2%) experienced surgical complications within 3 months after kidney transplantation, with hemorrhagic complications being the most frequent.
Previous studies have reported surgical complications were associated with recipients or donor factors, such as recipient age, sex, BMI, donor age or deceased kidney donor (11-13). The present study found no recipient or donor factors predisposing surgical complications, but peri-operative factors, including blood loss, operation time and number of vascular anastomoses, were risk factors for surgical complications. More vascular anastomoses may contribute to longer operation time and be a risk factor for blood loss. This finding is reasonable because post-operative hemorrhage and hematoma formation accounts for most of our surgical complications. In addition, more blood loss and prolonged operation time may contribute to higher risk of post-operative abscess or infection complications. These findings were compatible with the previous studies and provide the rationale to improve these peri-operative parameters (10, 13).
Despite improved surgical techniques, antibiotics treatment and optimal immunosuppressive regimens, we found that the operation year was associated with more surgical complications. Wong et al. also reported similar results (12). Indeed, kidney transplantation is typically conducted by experienced surgeons at our hospital, and different surgeons may not explain the finding. Furthermore, the open surgical technique for kidney transplantation has little since it first description by Kuss et al. in 1951 (14). A study conducted by Grodstein et al. confirmed that the influence of surgeon’s experience on graft survival were limited (15). Recent trends on using marginal kidney donors and recipients with co-morbidities may be the contributing factors (16-18).
Higher BMI is known to be associated with surgical complications (11, 13) and graft loss (19, 20). However, a systematic review conducted by Hill et al. reported that patients with higher BMI experience similar outcomes compared with normal (21). Zrim et al. reported on the other hand that a higher BMI was not related to higher surgical complications (22). Our present study found no association between BMI and graft survival nor surgical complications. Possible explanation may be that improved surgical techniques using subcutaneous suture during wound closure and proper drainage tube placement for those patients reduce their risks of surgical complications and graft failure.
Previously, studies reported that surgical complications are associated with poorer early graft survival (11, 13, 23, 24). In the present study, surgical complication was an independent predictive factor for both worse one-year death-censored graft survival and one-year mortality. This may be attributed to that patients with surgical complications requiring surgical intervention or percutaneous drainage are those more susceptible to infection or septic episodes than those without surgical complications. Since, infections accounted for most graft failure in both the present and the past studies (8, 25, 26).
The impact of surgical complications on graft survival would theoretically decrease as they stabilized over time (27). For long-term outcomes, the present study found interestingly that patients with surgical complications had worse death-censored graft survival and poorer survival. Previous studies have reported similar results (11, 12). The possible explanation may be that the length of follow-up duration in the present study, though with a mean follow-up duration of 7.8 years, was not long enough for the effects to vanish. Further analysis is necessary to investigate the contributing factors for these results. Nevertheless, these findings indicate the influence of surgical complications persists for years and suggests the necessity of minimizing surgical complications for these patients.
The strength of this study was that all the data were collected from a single medical center with complete patient information and follow-up program. Furthermore, literature for Asia kidney transplantation was scarce and our study may provide information for these patients. In this study, we found that surgical complications were associated with both short-term and long-term outcomes. Risk factors for surgical complications were identified. These findings provide useful information for clinicians in kidney transplantation.
Study limitations. First, the retrospective design of the present study as well as relatively small number of patients may lead to bias. Second, the surgical complications included wound, urologic or vascular complications. Subgroup analyses, such as the effects of urologic complications, may be underpowered due to small patient number. However, the present study showed the long-term impact of surgical complication on graft survival and mortality, which was rarely reported in the previous literatures.
Conclusion
Surgical complications were associated with higher risk of both short-term and long-term death-censored graft failure and mortality. Cold ischemia time, blood loss, number of vascular anastomoses and operation time were risk factors for surgical complications. Efforts to minimize surgical complications are warranted to improve graft and patient survival.
Footnotes
Authors’ Contributions
Study design and conception: Gu-Shun Lai and Jian-Ri Li. Interpretation of data and drafting of the manuscript: Gu-Shun Lai. Acquisition of data: Jian-Ri Li, Shian-Shiang Wang, Chuan-Shu Chen, Chun-Kuang Yang, Chia-Yen Lin, Sheng-Chun Hung, Hao-Chung Ho, Yen-ChuanOu, Kun-Yuan Chiuand Shun-Fa Yang. Manuscript review: Shun-Fa Yang.
Conflicts of Interest
The Authors have no conflicts of interest to declare.
- Received July 22, 2023.
- Revision received August 27, 2023.
- Accepted September 1, 2023.
- Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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