Objectives: Lymphocele is a frequent complication after kidney transplant and needs attention. This study was undertaken to analyze perioperative risk factors and short-term outcomes associated with lymphocele after kidney transplant.
Materials and Methods: Our single-center study retrospectively analyzed 264 recipients of kidney allografts from January 2018 to October 2021. Patients were classified into 2 groups according to the occurrence of lymphocele. Perioperative clinical data and follow-up indicators were compared between groups.
Results: The incidence of lymphocele after kidney transplant was 19.7%. Univariate analysis showed that percentage of male patients, hypothermic machine perfusion proportion, and postoperative hemoglobin and albumin were lower and flow velocity of renal artery was higher in the lymphocele group compared with the control group. Multivariate logistic regression revealed that postoperative hemoglobin <95 g/L (odds ratio = 2.01; 95% confidence interval, 1.01-4.05; P = .03) was an independent risk factor and hypothermic machine perfusion (odds ratio = 0.27; 95% confidence interval, 0.08-0.96; P = .04) was a protective factor for the determination of lymphocele. Comparisons of related complications indicated that drainage tube and urinary catheter removal times were longer and urinary tract infection and moderate to severe anemia proportions were higher in the lymphocele group. Follow-up data showed that postoperative 1-month serum creatinine was higher and 1-month estimated glomerular filtration rate was lower in lymphocele group compared with the control group, but no significant differences were shown at 12 months.
Conclusions: Postoperative hemoglobin may be a risk factor and hypothermic machine perfusion may be a protective factor for lymphocele after kidney transplant. Lymphocele only temporarily affects short-term kidney function, especially during hospitalization.
Key words : Complication, Hemoglobin, Hypothermic machine perfusion, Follow-up, Renal transplantation
Kidney transplantation (KTx) is the best choice to treat end-stage renal disease, with higher survival rate and quality of life compared with continuous dialysis. With the implementation of extended criteria donor organs, challenges for transplant recipients have increased, such as delayed graft function (DGF), acute rejection, infection events, and metabolic disease.1 Consequently, the maintenance of the organ after transplant and hospitalization is essential for long-term survival.
Lymphocele formation after KTx is a common urological complication, with incidences ranging from 0.6% to 33.9%.2 Although lymphoceles are mainly asymptomatic, patients may present with acute rejection, edema, vein thrombosis, and urinary obstruction.3 Large and complicated lymphoceles that show risk to the organ usually need percutaneous puncture drainage or an open surgical procedure. Lymphoceles may be caused by the iatrogenic injury of the lymphatic system related to the donor kidney and recipient vessels. Different methods have been reported to deal with this issue, such as avoiding ultrasonic shears, precise ligation of lymphatic vessels, fluorescent lymphography, and peritoneal fenestration.4-6 However, lymphocele remains a troublesome complication after KTx.
In this retrospective study, we aimed to verify the incidence and perioperative risk factors of lymphocele in KTx recipients, as well as short-term outcomes.
Materials and Methods
In our single-center retrospective study, we analyzed 264 recipients of deceased or living donor KTx from January 2018 to October 2021 in the First Affiliated Hospital of Soochow University. The study was approved by the institutional ethics committee. Among 18 living donors, 17 were parents who donated to their children and 1 was a wife to husband. Ultrasonographic examinations of the transplanted kidney were routinely performed twice a week during hospitalization and once per month in the first transplant year. All lymphoceles were diagnosed within 6 weeks after KTx. Pediatric recipients, patients with secondary transplants or combined liver and kidney transplants, and patients who had kidney loss within 1 month and perirenal hematoma were excluded from the analysis (Figure 1). Patients were divided into 2 groups based on the occurrence of lymphocele.
Ethics approval and consent to participate
The study was approved by the institutional ethics committee of The First Affiliated Hospital of Soochow University and followed the principles outlined in the Declaration of Helsinki.
Transplant procedures were performed using standard extraperitoneal technology by experienced surgeons in our center. Briefly, the donor kidney was meticulously trimmed by forceps and tissue scissors. The redundant vascular vessels and open lymphatic vessels in the renal sinus region were sufficiently ligated by 3-0 silk suture to minimize lymphorrhea. After perfusion, the graft was then placed in the right or left fossa iliaca. During the transplant surgery process, we commonly used an ultrasonic knife and electric knife to separate tissues and blood vessels to expose the recipient’s vascular vessels and 3-0 silk suture to ligate potential lymphatic vessels near the iliac vascular region. The kidney artery was anastomosed end-to-end to internal iliac artery or end-to-side to external iliac artery depending on the vascular condition. The kidney vein was anastomosed end-to-side to external iliac vein, and then ureteroneocystostomy with a double J-catheter implantation was achieved.
We collected preoperative data on donor status (living or deceased), donor age, donor sex, donor terminal creatinine level and recipient age, sex, body mass index (BMI), blood glucose, triglyceride, hemoglobin, albumin, dialysis style, hypothermic machine perfusion (HMP), and HLA mismatches. Data collected from 1 day after transplant included recipient hemoglobin, albumin, kidney length, resistance index (RI), aorta flow velocity (FV), cold ischemia time, warm ischemia time (WIT), operation time, and immunity induction. Drainage tube, urinary catheter, and ureteral stent removal times; length of hospital stay; presence of urinary tract infection (UTI), wound infection, diabetes mellitus, and moderate to severe anemia; DGF; and acute rejection proportions that occurred during hospitalization were also analyzed. Follow-up data included postoperative 1-month creatinine and estimated glomerular filtration rate (eGFR) and postoperative 12-month creatinine and eGFR.
Lymphoceles were diagnosed by routine ultrasono-graph imaging with perigraft fluid collection diameter >5 cm, with exclusion of urinoma, hematoma, and abscess.7 Delayed graft function was defined as the need for hemodialysis within the first week after transplant.8 Rejection episodes such as T-cell-mediated or antibody-mediated rejections were confirmed by biopsies according to the BANFF 2019 criteria.9 Infection events were reflected by positive culture in urine or wound drainage.10 Hemoglobin <90 g/L was identified as moderate to severe anemia.11 The diagnose of diabetes mellitus was fasting glucose ≥7 mmol/L or random glucose ≥11.1 mmol/L, as previously described.12 Before transplant to patients, kidney grafts underwent HMP or static cold storage, depending on operating room capacity and matching matters. The LifePort (Organ Recovery Systems) and UW Solution (Belzer MPS) were used for HMP.
We used IBM SPSS version 25 (IBM Corp) for statistical analysis. Categorical variables are shown as proportions and frequencies, and differences between groups were assessed by using the Fisher exact test or the chi-square test, as appropriate. Continuous data are shown as means ± SD or median (interquartile ranges), and differences were assessed with independent t-test or the Mann-Whitney U test. The significant clinical data (recipient male, postoperative albumin, postoperative hemoglobin, FV, and HMP) were included in the full variable model multivariate logistic regression for further determination of independent risk factors for lymphoceles. P < .05 was considered significant.
Between 2018 and 2021, 264 patients underwent KTx at our center; after exclusion criteria, our study included 239 patients (Figure 1). The incidence of lymphoceles was 19.7% (47/239). The average diameter of the lymphocele was 6.96 ± 1.50 cm. The mean recipient age was 43.4 ± 10.2 years, mean BMI was 22.0 ± 3.3, and 36.8% of patients were female. The common primary diseases were glomerulonephritis (52.7%) and hypertensive renal disease (9.6%). Of 47 patients with lymphoceles, 3 (6.4%) were diagnosed as symptomatic cases. Among these patients, average diameter was 10.40 ± 1.06 cm, 2 patients had abdominopelvic discomfort, and 1 patient presented as limb edema. For all 3 patients, percutaneous puncture drainage was performed, and discomfort disappeared in the next few days.
The proportion of male recipients in the control group was higher than in the lymphocele group (66.7% vs 48.9%; P = .02). The preoperative hemoglobin and albumin levels were not significantly different (P > .05), whereas postoperative 1-day hemoglobin and albumin were both lower in the lymphocele group compared with the control group (P < .01). Flow velocity of transplanted kidney in lymphocele recipients was higher than in the control group (184.24 ± 70.73 vs 161.85 ± 55.29 cm/s; P = .04). We also found HMP proportion was lower in the lymphocele group compared with the control group (6.4% vs 19.3%; P = .03). We found no significant difference regarding donor age, male proportion, and creatinine level. Recipient age, BMI, kidney length and RI, dialysis style, WIT, cold ischemia time, operation time, HLA mismatch, and immunity induction were not significantly different between the lymphocele group and the control group (P > .05) (Table 1).
Risk factors and complications for lymphocele
Multivariate logistic regression analysis showed that postoperative hemoglobin was associated with a higher risk (odds ratio = 2.01, 95% confidence interval, 1.01-4.05; P = .03) for the occurrence of lymphocele, whereas the use of HMP showed a lower risk (odds ratio = 0.27, 95% confidence interval, 0.08-0.96; P = .04) (Table 2).
Drainage tube removal time (15.67 ± 6.48 vs 13.50 ± 5.10 days; P = .02) and urinary catheter removal time (11.66 ± 4.17 vs 10.23 ± 3.31 days; P < .01) were significantly longer in the lymphocele group compared with the control group. Urinary tract infection (38.3% vs 23.4%; P = .04) and moderate to severe anemia (68.1% vs 50.5%; P = .03) were significantly more frequent in the lymphocele group during the observation period. However, presence of wound infection (8.5% vs 6.3%; P = .53), diabetes mellitus (14.9% vs 13.0%; P = .73), DGF (25.5% vs 18.8%; P = .30), and acute rejection (4.3% vs 4.2%; P = 1.00) were similar between the 2 groups (Table 3).
Short-term prognosis of lymphocele recipients
Creatinine levels were significantly higher (141.88 ± 89.94 vs 112.24 ± 74.53 ?mol/L; P = .02) and eGFR results were significantly lower (61.08 ± 30.74 vs 70.17 ± 25.71 mL/min/1.73 m2; P = .04) in the lymphocele group at 1 month after KTx compared with the control group (Table 4). Nevertheless, there was no significant difference in creatinine or eGFR between the 2 groups at 12 months postoperatively (P > .05).
Lymphocele complications after KTx are a common but difficult urological event. Although most lymphoceles are asymptomatic and require nonsur-gical treatment, growing evidence has shown that some complex lymphoceles may affect the quality of life of patients and even result in reoperations or graft loss.2,13 Lymphocele complications can also increase the financial burden for recipients. Hence, studies have focused on postoperative outcomes and risk factors of lymphoceles. A number of medical risk factors, such as DGF, use of ultrasonic shears, longer drainage duration, external iliac artery, anastomosis, and WIT have been reported to affect the formation of lymphoceles.3,14,15 However, few studies have investigated the prevention of lymphoceles, especially in the perioperative period. Simforoosh and colleagues suggested that bipolar cautery was a simple and effective method to prevent postoperative lymphocele in living donor and deceased donor KTx recipients.16,17 Golriz and colleagues reported that intraoperative peritoneal fenestration could reduce formation of severe lymphoceles.13 Because of data heterogeneity, the results cannot be simply com-pared. We undertook this study to observe perioperative risk factors of lymphoceles in KTx recipients and short-term transplant organ outcomes.
In our study, we used silk suture to ligate the lymphatic vessels of the donor and recipient. The incidence rate of lymphoceles among our KTx recipients was 19.7%. Most patients were asymp-tomatic and diagnosed within 6 weeks after transplant by routine ultrasonograph examination. Because of high sensitivity and specificity, ultrasonographs can quickly and effectively distinguish blood clot or infective pus from a lymphocele. Ultrasound-guided puncture has been shown as a valid diagnosis and treatment method.18 For the 3 symptomatic lymphocele cases in our study, patient discomfort may have been because of compression of the organ or inguinal vessels by the huge size of the lymphocele. The 3 patients were treated successfully by ultrasound-guided percu-taneous puncture with prolonged drainage tube removal time. These lymphoceles were located within the fossa iliaca and easy to puncture, and there was no serious comorbidities, such as wound dehiscence, and no recurrence during follow-up.
We used vascular ultrasonographs to observe RI and FV, which were important parameters for a transplanted kidney.19 Although univariate analysis showed that FV of kidney artery in the lymphocele group was higher than the control group, FV was not significant in subsequent multivariate analysis, and there were no other vascular events, such as thrombus, among lymphocele cases. Consequently, we were more inclined to believe that the lymphocele might rarely cause a pressure effect on allograft vessels.
Among medical risk factors, we interestingly found that postoperative hemoglobin of <95 g/L was associated with lymphocele formation. This finding may have originated from leakage of both unligated lymphatic vessels and near veins of the recipient or transplanted kidney. An acute decrease in hemoglobin was probably because of intraoperative bleeding or excessive fluid supplement.20 Meanwhile, perioperative changes in hemoglobin reduced oxygen delivery to glomerulus and tubules, which may result in acute kidney injury and poor early graft function.11
Similarly, in subsequent comparisons, the pro-portion of moderate to severe anemia was higher in the lymphocele group. Posttransplant anemia was associated with a decline in GFR and with reduced graft survival and mortality.21 Hence, the early application of erythropoietin or timely blood transfusion is vital to improve anemia symptoms and organ perfusion.22,23
Of note, we also found that the use of HMP was a protective factor for the occurrence of lymphoceles. Compared with static cold storage, HMP has been shown to be superior in ameliorating ischemia-reperfusion injury, decreasing the risk of DGF, and improving long-term survival.24 The underlining mechanisms might be related to inflammatory factor levels, endothelial dysfunction, cell death, and immune responses.25 Some evidence has shown that the inflammatory process could increase the fluid flow from lymphatic vessels around the iliac vessels and that rejection episodes had a role in the formation of lymphocele.3,14 Although this mechanical method was not routine used in our center, the frequency of lymphocele decreased to 7.5% when HMP applied. Thus, HMP was likely to inhibit the progress of lymphocele formation through anti-inflammatory or immunomodulatory mechanisms.
Another medical factor associated with lymphocele was drainage tube removal time, which is consistent with other studies. Indeed, long postoperative drainage was reported to result in a higher chance of symptomatic lymphocele. However, we prefer it as a complication rather than a risk factor of lymphocele because the diagnosis of lymphocele will affect the decision of drainage removal.
Surprisingly, we found that the proportion of UTIs but not wound infections was higher in the lymphocele group. Urinary tract infections are the most common infection after KTx but could negatively affect graft and patient survival.10 Hence, the use of sensitive antibiotics and an appropriate immunosuppression scheme is necessary once UTI has been confirmed.26 Severe UTI such as bacteremia could lead to lymph node hyperplasia and an increase in the incidence of lymphocele.27 However, all of the UTI cases in our cohort were asymptomatic or mild symptomatic and underwent timely cure. Of note, HMP might reduce inflammation factors and may have also likely decreased the incidence of UTI and lymphocele. We believed that UTI was probably catheter-related because of the longer urinary catheter removal time in the lymphocele group. Ureteral stent removal time can exceed 4 weeks.28,29 The duration of urinary catheter placement varies across institutions, ranging from 2 days to more than 10 days postoperative. However, a lack of high-quality randomized controlled trials has prevented comparisons of early catheter removal versus late catheter removal in KTx.30 In our transplant center, we prefer to leave the catheter in situ for >7 days. The catheter could be left longer in the lymphocele group, with concerns of anastomotic breakdown and urinary leaks. Thus, it is inappropriate to remove the catheter too early because the transplanted kidney may not be completely fixed in the first week posttransplant and because of safety concerns of ureter-bladder anastomosis.
Analysis of patients at follow-up showed that postoperative 1-month creatinine was higher and eGFR was lower in lymphocele patients compared with control patients, although postoperative 12-month creatinine levels and eGFR results were not significantly different between groups. Creatinine and eGFR are accurate and sensitive indicators that are often used in long-term monitoring after KTx.31,32 We did not find any obvious distinction in the incidence of DGF and acute rejection, which were closely linked with organ function and prognosis. These results combined implied that lymphocele formation may have only temporarily affected short-term kidney function, especially during hospita-lization, but did not affect the long-term survival of the transplanted kidney.
This retrospective study had some limitations. First, because of the small group sizes, lymphoceles were not further graded on the basis of the severity and management strategy. Indeed, most of identified lymphoceles required no intervention in our cohort, although symptomatic lymphoceles have been reported to be associated with poor graft function. We mainly focused on clinical data in the perioperative or hospitalization period and were not concerned about the persistent time of lymphoceles. The etiology of lymphoceles was not discussed; further prospective and interventional researches are thus suggested. Although our study may have had selection bias and confounding bias, the results were interpretable, and further research, such as a randomized trial on HMP, is needed to confirm the reliability of results. Finally, the routine ultrasonograph examination was a simple but convenient method for tracking changes in lymphoceles or other related complications such as hematoma, vasculopathy, and urinary obstruction.
Although lymphoceles may have no effect on long-term function of the transplanted kidney, they deserve attention, not only because of the high incidence but also because of concomitant anemia and UTI events. The use of HMP may be related to low incidence of lymphoceles.
Volume : 21
Issue : 10
Pages : 807 - 813
DOI : 10.6002/ect.2023.0138
From the 1Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China; and the 2Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
Acknowledgements: The authors gratefully acknowledge the B-ultrasound team for the results used in this study. This study was funded by National Natural Science Foundation of China 82270787. The authors have no declarations of potential conflicts of interest.
Corresponding author: Xuedong Wei or Jianquan Hou, No. 899 Pinghai Road, Gusu District, Suzhou City, Jiangsu Province, China
E-mail: firstname.lastname@example.org or email@example.com
Figure 1. Flow Chart Showing Selection of Patients
Table 1. Comparison of Clinical Data Between Lymphocele Group and Control Group
Table 2. Multivariate Logistic Regression Analysis of Risk Factors of Lymphocele
Table 3. Comparison of Complication Indicators Between Lymphocele Group and Control Group
Table 4. Prognosis Comparison Between Lymphocele Group and Control Group