Key words : Kidney transplantation, Laparoscopic fenestration, Laparoscopic marsupialization, Percutaneous sclerotherapy

Introduction

Kidney transplant is the best treatment option for patients with end-stage kidney disease.¹ This intervention significantly reduces the risk of death (60%), doubles the expected survival time, and improves the quality of life.² In 2018, there were 12 832 kidney transplants performed in Latin America, according to the Spanish National Transplant Organization. In Colombia, in 2019, approximately 1000 kidney transplants were performed.

Although kidney transplant is an intervention that improves the quality of life of the recipients, the incidence rate for complications is 15% to 17%.³ These complications can be divided into medical and surgical aspects. Surgical complications can be vascular or urological problems, lymphoceles, wound infections, and hernias.⁴ Medical complications are not a part of this review.

Lymphocele, as the focus of this review, is a common postoperative complication in kidney transplant recipients. Given multiple forms of presentation and treatment, we aimed to describe the current concepts for this complication and propose a management algorithm.

Definition

Lymphoceles correspond to lymphatic fluid accu-mulation, surrounded by a pseudo membrane, near the transplanted kidney.^5,6 Most lymphoceles develop early after transplant but generally occur 2 weeks to 6 months after the procedure. Lymphoceles have a peak of incidence at 6 weeks and are frequently detected before clinical symptoms.^7,8

Epidemiology

Previous studies have reported the incidence of symptomatic lymphoceles between 0.6% and 26% after kidney transplant.^2,4,9-11

Pathogenesis

The pathogenesis of a lymphocele has 2 essential steps. First, there is lymph drainage out of the lymphatic vessels, which collects in the retroperitoneal space around the transplanted kidney.¹² Later, a fibrous capsule forms and covers the lymphocele, making its resolution more complex. In such a way, lymphatic vessel injury plays an essential role in lymphocele development.¹²

Risk Factors

Assessment of individual risks before and after transplant could facilitate specific diagnoses and treatment for a patient.¹³ Some factors have been implicated in the development of lymphoceles, which include the recipient’s age, sex, body mass index, dialysis time, type of donor (deceased), extensive perivascular dissection during native vessel mobilization, capsular tears, episodes of acute rejection, a biopsy of the graft, presence of arteriovenous fistulas in the lower limb, use of diuretics, and high doses of corticosteroids and anticoagulants, among others.^14,15

Heer and colleagues⁸ found that the cumulative prednisone dose at 3 months is a risk factor for lymphocele development. No significant differences were found for age, donor type, single versus multiple arteries, ischemia time, or fluid balance. Pacovsky and colleagues¹² found that male sex is a risk factor for lymphoceles, and they hypothesized that the reason may be differences in protein and albumin values for male versus female sex. Their study did not find meaningful differences in age, body mass index, or dialysis time. Giuliani and colleagues¹⁵ found that age ≧11 years, body mass index ≧95% percentile for age, male sex, and donor type (deceased) are risk factors for lymphocele formation. They also suggested that there could be twice the risk of graft loss in patients who develop lymphoceles versus patients with no lymphoceles. However, there were no statistically significant results to support this hypothesis. Presently, there is a scarcity of studies that adequately evaluate the relationship of these factors with the condition.

Prevention

The development of new technologies and advances in surgical techniques have decreased the risk of lymphocele formation. The use of bipolar elec-trothermal devices in surgical dissection may prevent lymphocele formation compared with electrocautery methods, creating a fusion of vessels using a combination of pressure and energy. These changes denature the collagen, elastin fibers, and the rest of the connective tissue within the vessels, which allow the proteins to form a seal and thereby fuse the walls. In this way, the lumen is theoretically obliterated.¹⁶

Other authors have described the use of povidone-iodine immediately after transplant, and it has been shown to reduce lymphocele formation, given its sclerosing action.¹⁷ Use of polyethylene glycol sealants during surgery has been useful to prevent lymphocele formation without significant adverse effects.¹⁸

Clinical Presentation

The clinical presentation of a lymphocele varies from an asymptomatic liquid collection, to mild symptoms that are easily managed, to severe symptoms that can result in significant morbidity.¹⁹ The symptoms are generally produced by an expansive growth of the fluid, which generates a compression effect on the adjacent organs or the graft itself. Thus, the clinical presentation of lymphoceles can be divided into 3 broad groups of symptoms: urological, vascular, or visceral.¹

Urological symptoms

The elevation of creatinine values is one of the most frequent signs of lymphocele formation and is most often caused by the ureteral compression of the transplanted kidney, which leads to secondary hydronephrosis, renal dysfunction, and, consequently, elevation of renal function markers. Another pathophysiological mechanism that can lead to elevated creatinine is the compression of the renal vessels at the renal hilum.⁵

Lymphocele displacement of the bladder can lead to symptoms in the lower urinary tract, urinary frequency, dysuria, and urinary retention.

Vascular symptoms

Other symptoms are generated by the compression of vascular structures, iliac vessels, and even the vena cava, as well as edema of the lower limbs (with or without pain). Venous thrombosis and decreased vascular flow from the transplant may also occur.

Visceral symptoms

Visceral compression can cause abdominal discomfort and in some cases may generate compression wound dehiscence and may even present as intestinal obstruction. Another less frequent symptom is fever, which forces to rule out a lymphocele infection.¹⁹

Diagnosis

Diagnosis is generally made by ultrasonography combined with fluid aspiration to evaluate creatinine, lymphocytes, and gram stain results.⁶ Ultrasonography is the established standard for diagnostic imaging and offers the advantages of being noninvasive, safe, easily repeatable at frequent intervals, and unaffected by the degree of kidney dysfunction. Accordingly, follow-up protocols with ultrasonography have been applied immediately after transplant, at the peak of presentation of the lymphocele (4-8 weeks), and later at 6 and 12 months.²⁰

With ultrasonography, lymphoceles are visualized as either anechoic or hypoechoic. Fluid collections can be partitioned, small or large, to displace the kidney, and these are sonographically indistinguishable from other collections of simple fluid, such as urinoma and seroma.²⁰

Another diagnostic method is abdominal computed tomography with contrast, which can show well-defined collections of hypoattenuating fluids that generally have an attenuation value close to water.²⁰

There are no published studies regarding the comparative performance of these imaging techniques.

Treatment and Management Algorithm

Lymphocele treatment depends on its symptoms. Asymptomatic small collections do not require any treatment, and regular monitoring is sufficient. In contrast, large and symptomatic collections justify surgical intervention.

The following factors are considered necessary for proper therapy selection: severity of symptoms, size of the lesion, possible posttherapeutic complications, and the clinical condition of the patient.¹ The management of lymphoceles varies from aspiration or aspiration with sclerotherapy to more invasive techniques such as external or internal drainage. Recurrence in these treatments is high; however, laparoscopic marsupialization is the standard treatment in patients with failure of percutaneous drainage.⁵

Percutaneous Treatment

Ultrasonography-guided percutaneous aspiration is used for diagnosis and treatment. However, recur-rence rates are high, up to 75%.⁷ A previously published systematic review included 20 studies with 218 patients and reported a 59% rate of recurrence (95% CI, 10%-95%) for aspiration only.²¹ Percutaneous drainage with a pigtail catheter has resulted in recurrence rates of 25% to 50%. Prolonged duration (longer than 2 weeks) of the pigtail catheter seems to increase the success rate.¹² However, given the minimally invasive nature of the pigtail technique, it is considered a first-line treatment for lymphoceles.⁷ Some limitations that may hinder the success of percutaneous treatment are multilocular collections of fluid that complicate definitive drainage. Also, the puncture can be associated with lymphocele infection, since it converts a collection of sterile fluid to a collection with bacterial colonization.

The use of sclerosing agents for instillation in percutaneous management has produced encouraging results. However, this increases the possibility of surgical exploration in patients who do not respond due to the resultant scarring.¹⁰ Since 1983, povidone-iodine, a protein chelator, has been used as a sclerosing agent. Recurrence of 37.5% has been reported after the initial instillation and 18.7% after the second treatment.²² Other sclerosing agents include tetracycline, doxycycline, minocycline, fibrin gum, 95% ethanol, factor XIII, and fibrinogen. Lymphocele sclerotherapy is successful in 80% to 90% of cases, regardless of the agent used.²⁴ In a systematic review, Lucewicz and colleagues analyzed 14 studies and 144 patients and reported 31% recurrence for sclerotherapy.²¹ Opponents of sclerotherapy emp-hasize the possible risk of fibrosis around the transplant, mainly close to the ureter, which may add complexity to possible future procedures.²⁴

Surgical Treatment

If minimally invasive management of the lymphocele is unsuccessful, then surgical treatment is required. This approach has been described as marsupialization. Nevertheless, de-roofing and fenestration are more precise terms. A posttransplant lymphocele can be drained into the intraperitoneal space by opening the peritoneal wall connected to the lymphocele cavity, by either an open approach or laparoscopy.¹ Fenestration is rarely followed by recurrence, and therefore judged to be superior to other treatments, and as such it may become the standard of treatment.

The systematic review by Lucewicz and colleagues also included an analysis of 17 studies with 176 patients for which they reported 16% recurrence after open surgery and a rate of 8% for intrasurgical complications.²¹ The authors suggested open surgery as a promising treatment option in those patients for whom percutaneous management fails. In this same systematic review, they analyzed 22 studies and 322 patients with regard to laparoscopic surgery, for which they reported a recurrence rate of 8% and an intrasurgical complication rate of 8% (95% CI, 2%-20%).²¹ The length of hospital stay for patients treated with the open technique was 5.5 days, versus 2.5 days for the laparoscopic technique.²¹

Laparoscopic surgery is an adequate and practical option that shortens hospital stays and causes minimal patient discomfort,¹⁰ so it is considered the standard treatment for lymphoceles.

Intervention Proposal

With regard to the details we have reviewed, we suggest the management algorithm shown in (Figure 1).

Conclusions

Lymphocele formation is a frequent postoperative complication in kidney transplant recipients, with its most frequent presentation 6 weeks after surgery. Various factors have been implicated in posttransplant lymphocele formation, and some of the most meaningful factors are the use of corticosteroids, male sex, and deceased donor. The clinical presentation is variable, from small and asymptomatic collections to symptomatic collections with a high risk of morbidity that require some intervention. Treatment can begin with percutaneous treatment, and if it there is recurrence, then we suggest laparoscopic fenestration as the standard treatment.

Kidney transplant is the best treatment option for patients with end-stage renal disease, reducing mortality and improving quality of life. However, kidney transplant is associated with medical and surgical complications, and one of the most common is the posttransplant lymphocele.

Posttransplant lymphoceles require various degrees of intervention, and the first step should be percutaneous treatment. For subsequent lymphocele recurrence, we suggest laparoscopic fenestration should be the standard treatment. It can be started with percutaneous treatment, and if it recurs, we might offer laparoscopic fenestration as the standard treatment.

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