Current Evidence on Surgical Management for Benign Prostatic Hyperplasia in Renal Transplant Recipients: A Systematic Review.

Background: Patients who have undergone renal transplant may have a concomitant benign prostatic hyperplasia (BPH), a condition that can potentially hinder the recovery of the renal graft and necessitate surgical intervention. However, endoscopic treatment of BPH should be performed carefully because of the associated perioperative risks. We aimed to systematically assess the factors affecting surgical indications and perioperative outcomes of BPH surgical treatment in renal transplantation (RT) recipients. Methods: A systematic literature search was performed on January 28, 2023, using Scopus, PubMed, and EMBASE with no date limit. Preclinical and animal studies, reviews, letters to the editor, case reports, and meeting abstracts were excluded. Results: Eighteen articles were accepted and included. Clinical BPH has a high incidence rate after RT, particularly in elderly men. Secondary events associated with BPH, such as acute urinary retention and urinary tract infections, can lead to a gradual decline of renal graft function and patient survival. BPH procedure can prevent these events and guarantee improvements in serum creatinine levels, voiding parameters, and lower urinary tract symptoms. When the urine culture is negative, the endoscopic procedure of the prostate may be performed within 1 month of the initial procedure, particularly in older patients, more prone to develop voiding dysfunction. Alternatively, a transurethral incision of the prostate may be recommended for patients with smaller prostates who wish to preserve ejaculatory function. Data on comparative BPH surgical procedures are lacking. Conclusions: BPH procedure should be offered in RT recipients who develop bladder outlet obstruction owing to BPH. Endoscopic treatment should be performed after a few weeks from RT to avoid further graft deterioration.

Clinical progression of megacalycosis in a girl with a solitary kidney: The lesson learned.

Introduction: Megacalycosis is a rare disorder related to congenital underdevelopment of the renal papilla or structural defect of the renal calyces. Megacalycosis has a wide spectrum of clinical presentations ranging from simple variants without any significance on renal function to severe complications. Any prevention strategy is recommended yet since megacalycosis is mostly asymptomatic and usually discovered either accidentally or as result of its complications. Case presentation: We observed megacalycosis progression in a young female with a single kidney toward progressive calyx dilatation for years, which ended in acute pyelonephritis. Conservative management, urinary drainage, and large-spectrum antibiotics were unsuccessful and nephrectomy was required. Conclusion: This rare case and literature review add evidence to identify prognostic factors to select patients with a high risk of complications (single kidney, bilateral disease, female gender, associated genetic syndromes, vesicoureteral reflux, and contralateral renal disorder). One o more factors should activate close monitoring and prophylactic therapy if needed.

Case report: A hybrid technique for a safe nephrectomy in a giant kidney angiomyolipoma.

Background: Giant angiomyolipoma is usually associated with genetic syndromes and complications (spontaneous rupture and bleeding, hematuria, hypertension) and mass-related symptoms (flank and abdominal pain). Case presentation: We present a case of a 20-year-old woman suffering from tuberous sclerosis who was referred to our hospital with a giant angiomyolipoma causing abdominal pain. A contrast-enhanced computed tomography showed a left angiomyolipoma, measuring 28 cm × 17 cm × 27 cm. After a multidisciplinary team discussion, the patient was submitted for a nephrectomy. Percutaneous temporary occlusion of the main renal artery was achieved through an endovascular balloon catheter. Through the balloon catheter guidewire, 2,500 IU of heparin was infused to reduce the risk of tumor vein thrombosis and venous embolism. This allowed a safe kidney manipulation through a left thoracoabdominal approach. The postoperative course was uneventful. Pathology showed a 40 cm × 30 cm × 9 cm and 10 kg AML. One year after surgery, the patient is on follow-up, and her estimated glomerular filtration is 120.5 ml/min/1.73 m2. Conclusion: The present case showed that the endovascular control of the main renal artery could be considered a useful approach to safely managing huge renal masses when renal hilar control is expected to be very difficult.

Headache changes after kidney transplant.

Headache is considered as a possible complication of dialytic treatment in chronic kidney disease (CKD). The aim of this study was to evaluate possible change in headache characteristics after kidney transplantation in patients with CKD. During a 1-year period, we enrolled 110 subjects submitted to a kidney transplant in the previous 5 years. Headache characteristics before and after the transplant were investigated by a specific questionnaire. Possible effects of pharmacological therapies were also evaluated. 65.5% of patients complained of headache before the transplant (38.2% migraine and 14.5% dialysis headache). After transplant, 53.6% of patients reported changes in headache characteristics. In particular, 27.3% of the patients had a complete resolution, 19.1% presented a headache improvement and 7.2% showed a worsening. In both migraine and dialysis headache subgroups, steroids, beta-blockers and calcium channel blockers were associated with a significant improvement of headache. Kidney transplantation seems to impact significantly headache frequency and severity in patients with CKD. A careful evaluation and use of targeted treatments could improve both patients' compliance to therapies and quality of life.

ANCA-Associated Glomerulonephritis and Anti-Phospholipid Syndrome in a Patient with SARS-CoV-2 Infection: Just a Coincidence?

Many reports have described a high incidence of acute kidney injury (AKI) among patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to hemodynamic instability. However, other complex processes may be involved, related to the cytokine storm and the activation of innate and adaptive immunity. Here, we describe a patient who developed an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with rapidly progressive glomerulonephritis and lung involvement and an antiphospholipid syndrome soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After viral pneumonia was excluded by bronchoalveolar lavage, the patient has been treated with rituximab for amelioration of kidney function and resolution of thrombosis without any adverse event. We conclude that COVID-19 may trigger autoimmune diseases including ANCA-associated vasculitis. Thus, this diagnosis should be taken in consideration in COVID-19 patients, especially when they develop AKI with active urinary sediment. In addition, considering the relationship between these 2 diseases, SARS-CoV-2 infection should be excluded in all patients with a new diagnosis ANCA-associated vasculitis before starting immunosuppressive therapy.

COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

SARS-CoV-2 infection in kidney transplant recipients: Experience of the italian marche region.

BACKGROUND: Infection related to Coronavirus-19 (CoV-2) is pandemic affecting more than 4 million people in 187 countries worldwide. By May 10, 2020, it caused more than 280 000 deaths all over the world. Preliminary data reported a high prevalence of CoV-2 infection and mortality due to severe acute respiratory syndrome related CoV-2 (SARS-CoV-2) in kidney-transplanted patients (KTRs). Nevertheless, the outcomes and the best treatments for SARS-CoV-2-affected KTRs remain unclear. METHODS: In this report, we describe the clinical data, the treatments, and the outcomes of 5 KTRs with SARS-CoV-2 admitted to our hospital in Ancona, Marche region, Italy, from March 17 to present. Due to the severity of SARS-CoV-2, immunosuppression with calcineurin inhibitors, antimetabolites, and mTOR-inhibitors were stopped at the admission. All KTRs were treated with low-dose steroids. 4/5 KTRs were treated with hydroxychloroquine. All KTRs received tocilizumab up to one dose. RESULTS: Overall, the incidence of SARS-CoV-2 in KTRs in the Marche region was 0.85%. 3/5 were admitted in ICU and intubated. One developed AKI with the need of CRRT with Cytosorb. At present, two patients died, two patients were discharged, and one is still inpatient in ICU. CONCLUSIONS: The critical evaluation of all cases suggests that the timing of the administration of tocilizumab, an interleukin-6 receptor antagonist, could be associated with a better efficacy when administered in concomitance to the drop of the oxygen saturation. Thus, in SARS-CoV-2-affected KTRs, a close biochemical and clinical monitoring should be set up to allow physicians to hit the virus in the right moment such as a sudden reduction of the oxygen saturation and/or a significant increase in the laboratory values such as D-dimer.

Potential Applications of Extracellular Vesicles in Solid Organ Transplantation.

Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.

Changes in Cytokines, Haemodynamics and Microcirculation in Patients with Sepsis/Septic Shock Undergoing Continuous Renal Replacement Therapy and Blood Purification with CytoSorb.

BACKGROUND: Extracorporeal blood purification therapies have been proposed as a strategy to remove inflammatory mediators during sepsis, thus improving outcome. OBJECTIVES: We aimed to evaluate changes in cytokines, haemodynamics and microcirculation during blood purification with Cytosorb adsorber in septic patients. METHODS: Prospective observational study on critically ill adult patients with sepsis/septic shock underwent renal replacement therapy (RRT) for acute renal failure and haemoadsorption with Cytosorb as adjunctive therapy for 24 h. Measurements were taken at baseline, after 6 and 24 h: haemodynamic parameters, arterial and central venous blood gases, plasma levels of tumour necrosis factor alpha, interleukin (IL) 1-beta, IL-6, IL-8 and IL-10. The sublingual microcirculation was assessed with sidestream dark field videomicroscopy to evaluate the perfused vessel density (PVD) and microvascular flow quality. Tissue oxygenation and microvascular reactivity were assessed with thenar near infrared spectroscopy (NIRS) with a vascular occlusion test. RESULTS: Nine patients; plasma levels of IL-8 decreased at 24 h (p < 0.05 versus 6 h); no significant variation was found for other cytokines. Haemodynamic remained stable throughout the observation. Microvascular perfusion improved over time, with an increase in PVDs at 6 and 24 h (from 13.9 [13.3-16.4] to 15.7 [15-17.3] and 17 [14.8-18.6] mm/mm2 respectively, p = 0.003) and total vessel densities at 24 h (14.9 [13.9-16.9] vs. 17.9 [15.3-20], p = 0.0015). No significant variation was detected in NIRS-derived parameters. The Sequential Organ Failure Assessment score decreased from 12 ± 3 to 10 ± 1 at 24 h (p = 0.039). CONCLUSIONS: In septic patients undergoing RRT, haemoadsorption with Cytosorb seems to determine a decreasing in plasma levels of IL-8, although levels of other cytokines did not vary significantly, and an improvement of microcirculation despite no significant variation in macro-haemodynamics.

Extracellular Vesicles From Adipose Stem Cells Prevent Muscle Damage and Inflammation in a Mouse Model of Hind Limb Ischemia: Role of Neuregulin-1.

OBJECTIVES: Critical hindlimb ischemia is a severe consequence of peripheral artery disease. Surgical treatment does not prevent skeletal muscle impairment or improve long-term patient outcomes. The present study investigates the protective/regenerative potential and the mechanism of action of adipose stem cell-derived extracellular vesicles (ASC-EVs) in a mouse model of hindlimb ischemia. Approach and Results: We demonstrated that ASC-EVs exert a protective effect on muscle damage by acting both on tissue microvessels and muscle cells. The genes involved in muscle regeneration were up-regulated in the ischemic muscles of ASC-EV-treated animals. MyoD expression has also been confirmed in satellite cells. This was followed by a reduction in muscle function impairment in vivo. ASC-EVs drive myoblast proliferation and differentiation in the in vitro ischemia/reoxygenation model. Moreover, ASC-EVs have shown an anti-apoptotic effect both in vitro and in vivo. Transcriptomic analyses have revealed that ASC-EVs carry a variety of pro-angiogenic mRNAs, while proteomic analyses have demonstrated an enrichment of NRG1 (neuregulin 1). A NRG1 blocking antibody used in vivo demonstrated that NRG1 is relevant to ASC-EV-induced muscle protection, vascular growth, and recruitment of inflammatory cells. Finally, bioinformatic analyses on 18 molecules that were commonly detected in ASC-EVs, including mRNAs and proteins, confirmed the enrichment of pathways involved in vascular growth and muscle regeneration/protection. CONCLUSIONS: This study demonstrates that ASC-EVs display pro-angiogenic and skeletal muscle protective properties that are associated with their NRG1/mRNA cargo. We, therefore, propose that ASC-EVs are a useful tool for therapeutic angiogenesis and muscle protection.

Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients.

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

PDGF enhances the protective effect of adipose stem cell-derived extracellular vesicles in a model of acute hindlimb ischemia.

We previously have shown that platelet-derived growth factor (PDGF) modulates the biological activity of extracellular vesicles released by adipose-derived mesenchymal stem cells (ASC-EVs). ASC-EVs may interact with blood and vessel cells by transferring proteins and nucleic acids and regulate their functions. In this study, we investigated immunomodulatory activity and protection from acute hindlimb ischemia of EVs released by PDGF-stimulated ASC (PDGF-EVs). PDGF treatment of ASC changed protein and RNA composition of released EVs by enhancing the expression of anti-inflammatory and immunomodulatory factors. In vitro, control EVs (cEVs) derived from non-stimulated ASC increased the secretion of both the IL-1b, IL-17, IFNγ, TNFα pro-inflammatory factors and the IL-10 anti-inflammatory factor, and enhanced the in vitro peripheral blood mononuclear cell (PBMC) adhesion on endothelium. In contrast, PDGF-EVs enhanced IL-10 secretion and induced TGF-ß1 secretion by PBMC. Moreover, PDGF-EVs stimulated the formation of T regulatory cells. In vivo, PDGF-EVs protected muscle tissue from acute ischemia, reduced infiltration of inflammatory cells and increased T regulatory cell infiltration in respect to cEVs. Our results suggest that PDGF-EVs are enriched in anti-inflammatory and immunomodulatory factors and induced in PBMC an enhanced production of IL-10 and TGF-ß1 resulting in protection of muscle from acute ischemia in vivo.

Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia.

Serum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodeling and prevented muscle damage in a mouse model of acute hind limb ischemia. e-sEV angiogenic proteomic and transcriptomic analyses show a positive correlation with matrix-metalloproteinase activation and extracellular matrix organization, cytokine and chemokine signaling pathways, Insulin-like Growth Factor and platelet pathways, and Vascular Endothelial Growth Factor signaling. A discrete gene signature, which highlights differences in e-sEV and ineffective-EV biological activity, was identified using gene ontology (GO) functional analysis. An enrichment of genes associated with the Transforming Growth Factor beta 1 (TGFß1) signaling cascade is associated with e-sEV administration but not with ineffective-EVs. Chromatin immunoprecipitation analysis on the inhibitor of DNA binding I (ID1) promoter region, and the knock-down of small mother against decapentaplegic (SMAD)1-5 proteins confirmed GO functional analyses. This study demonstrates sEV pro-angiogenic activity, validates a simple, sEV pro-angiogenic assay which predicts their biological activity in vivo, and identifies the TGFß1 cascade as a relevant mediator. We propose serum as a readily available source of EVs for therapeutic purposes.

The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury.

BACKGROUND: Mesenchymal stromal cells (MSCs) and renal stem/progenitors improve the recovery of acute kidney injury (AKI) mainly through the release of paracrine mediators including the extracellular vesicles (EVs). Several studies have reported the existence of a resident population of MSCs within the glomeruli (Gl-MSCs). However, their contribution towards kidney repair still remains to be elucidated. The aim of the present study was to evaluate whether Gl-MSCs and Gl-MSC-EVs promote the recovery of AKI induced by ischemia-reperfusion injury (IRI) in SCID mice. Moreover, the effects of Gl-MSCs and Gl-MSC-EVs were compared with those of CD133+ progenitor cells isolated from human tubules of the renal cortical tissue (T-CD133+ cells) and their EVs (T-CD133+-EVs). METHODS: IRI was performed in mice by clamping the left renal pedicle for 35 minutes together with a right nephrectomy. Immediately after reperfusion, the animals were divided in different groups to be treated with: Gl-MSCs, T-CD133+ cells, Gl-MSC-EVs, T-CD133+-EVs or vehicle. To assess the role of vesicular RNA, EVs were either isolated by floating to avoid contamination of non-vesicles-associated RNA or treated with a high dose of RNase. Mice were sacrificed 48 hours after surgery. RESULTS: Gl-MSCs, and Gl-MSC-EVs both ameliorate kidney function and reduce the ischemic damage post IRI by activating tubular epithelial cell proliferation. Furthermore, T-CD133+ cells, but not their EVs, also significantly contributed to the renal recovery after IRI compared to the controls. Floating EVs were effective while RNase-inactivated EVs were ineffective. Analysis of the EV miRnome revealed that Gl-MSC-EVs selectively expressed a group of miRNAs, compared to EVs derived from fibroblasts, which were biologically ineffective in IRI. CONCLUSIONS: In this study, we demonstrate that Gl-MSCs may contribute in the recovery of mice with AKI induced by IRI primarily through the release of EVs.

Characterization and Management of Cutaneous Side Effects Related to the Immunosuppressive Treatment in Solid Organ Recipients.

Patients who underwent solid organ transplantation frequently suffer from different skin diseases, as consequence of the immunosuppressive treatment. Specific cutaneous side effects such as acne, hypertricosis or other pilosebaceous unit disorders, gingival hyperplasia, purpura or teleangiectasies are commonly associated to immunosuppressive medications. The majority of these conditions are benign, but the aesthetic concern may affect the patient is quality of life and reduce the adherence to the therapy. Moreover, solid organ transplant recipients frequently develop skin infections, as an indirect consequence of the immunosuppressive regimens. Herpes virus reactivation is more common few months after transplantation, whereas when the immunosuppression is reduced, the skin infections are mainly represented by human papilloma virus infections and localized mycosis. Bacterial infections are relatively rare. Long-term consequences of the immunosuppressive therapy are represented by development of precancerosis and skin cancers, with a risk that enhances over the time and a significant impact on patient survival. The aim of this paper is to provide an overview of the data published in the recent literature about this topic, in order to characterize the main skin disorders associated to the use of immunosuppressive drugs in solid organ recipients, giving information about their risk, epidemiology, clinical manifestations and management.

Extracellular vesicles as new players in angiogenesis.

Growing evidence suggests that small vesicles actively released from cells may encapsulate transcriptional regulators and RNA molecules. Their ability to interact with neighbouring cells and/or with distant cells through biological fluids, makes them a medium through which intercellular exchange of information can happen. Recently, membrane vesicles, which include exosomes and microvesicles, gained a place amongst the vast group of angiogenic mediators. In the present review we discuss the potential relevance of these vesicles in physiological and pathological situations of angiogenesis as well as their mechanism of action.

Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation.

Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2α (PI3K-C2α) in renal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2α resides at the recycling endosome compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2α controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. Consistently, partial reduction of PI3K-C2α was sufficient to impair elongation of the cilium and the ciliary transport of polycystin-2, as well as to alter proliferation signals linked to polycystin activity. In agreement, heterozygous deletion of PI3K-C2α in mice induced cilium elongation defects in kidney tubules and predisposed animals to cyst development, either in genetic models of polycystin-1/2 reduction or in response to ischemia/reperfusion-induced renal damage. These results indicate that PI3K-C2α is required for the transport of ciliary components such as polycystin-2, and partial loss of this enzyme is sufficient to exacerbate the pathogenesis of cystic kidney disease.

Lymphatic disorders after renal transplantation: new insights for an old complication.

In renal transplanted patients, lymphoceles and lymphorrhea are well-known lymphatic complications. Surgical damage of the lymphatics of the graft during the procurement and of the lymphatic around the iliac vessels of the recipients has been associated with development of lymphatic complications. However, lymphatic complications may be related to medical factors such as diabetes, obesity, blood coagulation abnormalities, anticoagulation prophylaxis, high dose of diuretics, delay in graft function and immunosuppressive drugs. Consistently, immunosuppression regimens based on the use of mTOR inhibitors, especially in association with steroids and immediately after transplantation, has been associated with a high risk to develop lymphocele or lymphorrhea. In addition, several studies have demonstrated the association between rejection episodes and lymphatic complications. However, before the discovery of reliable markers of lymphatic vessels, the pathogenic mechanisms underlining the development of lymphatic complications during rejection and the influence of mTOR inhibitors remained not fully understood. The recent findings on the lymphatic systems of either native or transplanted kidneys together with the advances achieved on lymphangiogenesis shared some lights on the pathogenesis of lymphatic complications after renal transplantation. In this review, we describe the surgical and medical causes of lymphatic complications focusing on the rejection and immunosuppressive drugs as causes of lymphatic complications.