Surgical Complications After Kidney Transplantation

Introduction

Kidney transplantation (KT) is the best therapeutic option in patients with end-stage kidney disease. Despite improving the patient’s quality of life, kidney transplantation remains one of the surgical procedures associated with the risk of surgical complications. The overall incidence of surgical complications ranges between 5% and 38% [1]. They can be further divided into urological, vascular, and other complications, including fluid collections (lymphocele/lymphorrhea, hematomas), wound infection, wound dehiscence, and herniation [2,3]. Urological complications are the most common, with incidence rates ranging from 2.5% to 30% [4]. The major urological complications include urinary leakage and ureteral stenosis [5].

Approximately 90% of all of ureteral stenosis cases are caused by ischemia. The distal part of the ureter is the most vulnerable. To avoid ischemia, it is important to protect the “golden triangle” – preserving lower-pole accessory arteries (supplying the distal ureter) and periureteral tissue of the donor kidney [2]. Technical errors also contribute to this condition. Risk factors for delayed ureteral stenosis include BK virus, rejection, or recurrent infection. Hydronephrosis on ultrasonography, either with or without a decrease in urine output and a decline in glomerular filtration rate, indicates ureteral stenosis and typically necessitates surgical intervention. The treatment of ureteral stenosis typically involves an open repair, such as ureteroneocystostomy or ureteropyelostomy, which is dependent on the location and length of the stenosis. If the open approach is not safe, the endourological approach (eg, antegrade or retrograde balloon dilatation) or chronic ureteral stenting can be considered [6]. Arpali et al found that ureteral stenosis is the only urological complication that negatively impacts long-term graft survival [7]. Urinary leaks generally occur at the site of the ureteroneocystosomy, which can appear in drains or through the wound. This can result in prolonged healing, infection, or the formation of an abscess due to leakage of infectious urine. Pain or swelling around the transplanted kidney, a rise in creatinine, a decrease in urine output, and elevated inflammatory parameters are possible clinical manifestations [2,8]. Vascular complications are the most serious due to the high risk of graft loss. They encompass stenosis or thrombosis of the renal artery or vein, less common aneurysms, dissection, and arteriovenous fistulas. Surgical errors, vessel torsion or compression, or anatomical variations (eg, multiple renal vessels or double ureters) can influence the occurrence of vascular complications, with an overall incidence ranging from 3% to 15% [3]. Lymphoceles are fluid collections that can compress grafts and cause decreased graft function or, more seriously, deep vein thrombosis. During the early post-transplantation period, there can be an increase in drain production or wound leakage. Clinically, lymphocele may be asymptomatic or present with pain, frequent urination, or edema of the lower extremities because of local compression. Ultrasonography serves as the primary diagnostic method. Depending on the size of the lymphocele, conservative management, spontaneous resorption, or aspiration with drain insertion can used [6]. To distinguish between lymphocele and urine leakage/urinoma, a sample is taken from the drain for examination of the creatinine value in the drain. In the case of lymphocele, the drain creatinine is comparable to the serum creatinine, whereas in the case of urine leakage, the drain creatinine level is significantly higher than the serum creatinine [9].

According to previous studies, there are potential risk factors for the development of surgical complications, such as age of the patient at the time of KT, sex, type of donor, previous transplantation, or comorbities of the recipient (eg, obesity, diabetes mellitus [DM], hypertension, heart disease, chronic obstructive pulmonary disease) [1]. The aim of our study was to analyze the independent risk factors of both donor and recipient in relation to the occurrence of surgical complications in the post-transplantation period.

Material and Methods

This retrospective study enrolled patients who underwent KT at University Hospital Martin between 2013 and 2023. The study included both living donor (LD) KT and deceased donor KT. The average follow-up time was 19.2 months after kidney transplantation (±6.1).

Surgical complications were diagnosed according to clinical presentation, renal parameters, and the use of ultrasonography or CT scans. Regardless of whether they received conservative treatment or required intervention, we included them in the study.

According to the Organ Procurement and Transplantation Network (OPTN) and the United Network for Organ Sharing (UNOS), the standard-criteria donor (SCD) is defined as a deceased donor younger than 50 years without any criteria assigned to the expanded-criteria donor listed below. The expanded-criteria donor (ECD) is defined as a deceased donor older than 60 years or aged 50–59 years with at least 2 of the following criteria: history of high blood pressure, cerebrovascular cause of death, or serum creatinine greater than 133 mmol/l. We used the SCD and ECD criteria, but ECD was defined only by age (deceased donors over 60 years), as we could not retrospectively ascertain the donor’s cause of death or the presence of arterial hypertension in the medical history. In 2014, UNOS presented the Kidney Donor Profile Index (KDPI) scoring system, which can better predict expected graft function and improves organ allocation efficiency compared to the SCD/ECD dichotomy. However, to maintain consistency and ensure a homogeneous patient cohort throughout the entire study period (2013–2023), we elected to retain the SCD and ECD terminology originally implemented at the start of data collection in 2013.

All transplants from a living donor were performed with the consent of the donor and, in special cases, the ethics committee – not for financial gain but to assist a family member.

The patient received either basiliximab or antithymocyte globulin as induction immunosuppression therapy, depending on their immunological risk. Basiliximab induction treatment was chosen for patients at low immunological risk, administering it on the day of KT and the fourth day after KT. Recipients at higher immunological risk received antithymocyte globulin at a cumulative dose of either 3.5 mg/kg or 6 mg/kg body weight. Methylprednisolone was administered intravenously at a dose of 500 mg before KT and on the first day after KT, then switched to the oral form of prednisone on the second day after KT. Antibiotic prophylaxis consisted of cefuroxim administered at a dose 1.5 g intravenously before KT and after KT twice every 8 hours at a dose of 750 mg or ciprofloxacin at a dose of 400 mg before KT and after KT twice every 12 hours at a dose of 200 mg for patients with penicillin allergy.

A mix of immunosuppressants was used after induction immunosuppression therapy. These included calcineurin inhibitors (tacrolimus-TAC), mycophenolic acid (MPA), and corticosteroids (prednisone). Trimethoprim-sulfamethoxazole at a daily dose of 960 mg was administered as a prophylactic measure against Pneumocystis jirovecii from the first day after KT until 6 months. Prophylaxis of cytomegalovirus (CMV) infection with valganciclovir was given in patients in whom antithymocyte globulin was chosen as induction immunosupression therapy at a dose 900 mg daily for 100 days. In the case of CMV IgG-negativity in the recipient and CMV IgG-positivity in the donor, valganciclovir was administered for 200 days at the therapeutic dose.

Baseline characteristics were observed for both the donor and the recipient at the time of KT. These included the recipient’s sex, age, body mass index (BMI), presence of DM, BK virus positivity, and induction immunosuppression therapy. The donor’s characteristics included the type of donor (SCD, ECD, or LD) and the transplant center from which the kidney was obtained. All operations were performed by visceral surgeons using the same surgical technique. The ureteral “double J” stent was routinely inserted into the anastomosed ureter during KT in all recipients and removed after 6 weeks in most cases. After KT, each patient had a urinary catheter inserted for at least 5 days.

After KT, we observed the incidence of surgical complications as well as the time of occurrence of these complications (in months). We also monitored independent risk factors that could influence the occurrence of surgical complications, including a kidney transplant from another transplant center, the recipient’s BMI at the time of KT, the presence of DM, BK positivity, and the use of antiplatelet therapy.

We used a certified statistical program, MedCalc version 13.1.2. (MedCalc Software VAT registration number BE 0809 44,640, Member of International Association of Statistical Computing, Ostend, Belgium). Comparisons of continuous variables between groups were carried out using parametric (t test) or non-parametric (Mann-Whitney) tests; associations between categorical variables were analyzed using the chi-square test and Fisher’s exact test, as appropriate. The association between baseline characteristics, studied risk factors, and surgical complications was assessed by univariable and multivariable logistic regression. The Cox regression hazard model was used for multivariate analysis of independent risk factors for surgical complications. Results are expressed as either standard deviation or median. A P value <0.05 was considered to be statistically significant.

Results

Over an 11-year period (2013–2023), 253 patients (68.1% males, 31.9% females) with end-stage kidney disease underwent kidney transplantation at University Hospital Martin. Table 1 presents the baseline characteristics of the study population. The mean recipient age at the time of KT was 45±13.9 years. Among the 253 patients, 204 received kidneys from SCD donors, 60 from ECD donors, and 21 from LD, and 32.6% of the kidneys came from another transplant center in Slovakia.

According to the immunological risk before kidney transplantation, induction immunosuppression with basiliximab was chosen in 67.7% of patients and antithymocyte globulin in 30.2%. No induction immunosuppressive therapy was given in 6 patients (2.1%). Among recipients, 26% had diabetes mellitus at the time of KT, andthe average BMI was 25.9 (±4.6 kg/m2). BK virus positivity was present in 5.3% of cases, BK viremia was around 15 000 (±6500) copies/ml, with a median of 1150 copies/ml.

Out of 253 kidney transplant recipients, 45 (15.8%) experienced surgical complications, as shown in Table 2. The average time for the onset of surgical complications after KT was 5.4 months. One of the most common surgical complications occurring most frequently in the first month after KT was bleeding, in a total of 6 patients, which accounted for 13.3% of cases. Lymphocele/lymphorrhea was present in 10 patients, with an overall incidence of 22.2%. The most common surgical complication in our study was ureteral stenosis, which was present in 27 patients, accounting for 60% of cases. The mean time of occurrence of ureteral stenosis was 7.8 months after KT. Other surgical complications (graft thrombosis and ileal perforation) were present in 2 patients, for a total of 4.5% of cases. Most (93%) surgical complications occurred in patients who were taking antiplatelet therapy at the time of KT.

Concerning the observed parameters in relation to surgical complications, 46.5% of surgical complications were in patients with diabetes mellitus. Only 12 patients with surgical complications in the whole cohort had BMI >30 kg/m2, which represented 27.9%. Observed parameters in relation to surgical complications are shown in Table 3.

In the next step, Cox proportional-hazard regression multivariate analysis was used to investigate the independent risk factors for surgical complications after KT. First, overall surgical complications alone were used as the endpoint, and then specific surgical complications (bleeding, lymphocele/lymphocele, and ureteral stenosis) were used, all listed in Tables 4–7. Using Cox proportional-hazard regression multivariate analysis, none of the observed parameters were identified as independent risk factors for the development of surgical complications. There were no significant differences in complication rates between recipients from deceased donors and living donors, and there were no significant differences in the recipient’s sex, age, or BMI, nor in the presence of diabetes mellitus or BK viremia.

Discussion

LIMITATIONS:

Our study’s retrospective nature prevented us from determining the donor’s cause of death, such as a cardiovascular event, stroke, or craniotrauma, leading us to categorize only those over age 60 years as ECD donors. We were also unable to assess the kidney’s anatomy, which appears to contribute to surgical complications, as well as the time of cold ischemia.

Conclusions

Surgical complications are an ongoing issue in the post-transplant period, which can lead to prolonged hospital stay and delayed onset of graft function. The aim is to minimize the incidence of surgical complications and thereby avoid the need for surgical reintervention. Recipient comorbidities (hypertension, diabetes mellitus, BMI at the time of KT), donor age, cold ischemia time, and total operative time can influence the incidence of surgical complications. Our study also confirmed that urological, vascular, and parietal complications are the most common surgical complications.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author, P.K.