|
1
|
Kassem AM, Al-Koraie AF, Shaalan WE, Elemam AA, Korany AO. Evidence-Based Complementary Benefit of the Vascular Surgeon Among the Team of Renal Transplantation; a Single Center Experience. Ann Vasc Surg 2024; 106:108-114. [PMID: 38387797 DOI: 10.1016/j.avsg.2023.12.077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 12/11/2023] [Accepted: 12/15/2023] [Indexed: 02/24/2024]
Abstract
BACKGROUND In a kidney transplant tertiary referral center; we compared 3 operating team configurations of different surgical specialties to highlight the effect of the operating surgeon's specialty on various operative details and procedural outcome. METHODS A total of 50 cases of living donor transplantations were divided into 3 main groups according to the operating surgeons' specialty, the first group (A) includes 12 patients exclusively operated on by urologists with advanced training in transplantation, the second group (B) includes 35 patients operated by combined surgical specialties; a urologist and a vascular surgeon both with advanced transplantation training, and a third group (C) includes 3 cases where the transplant operation commenced with operating urologists as in group (A) but required intraoperative urgent notification of a vascular surgeon to manage unexpected intraoperative technical difficulties or major complications. Cases were studied according to operative details, anastomosis techniques, ischemia times, total procedure time, recovery of urinary output, intensive care unit (ICU) stay, postoperative surgical complications and serum creatinine level for up to 3 years of follow-up. RESULTS Study of operative details revealed that total duration of graft ischemia was significantly shorter in group (B) and significantly longer in group (C) (P value 0.001), Total procedural duration also varied significantly between the 3 groups, group (B) being the shortest while group (C) was the longest (P value less than 0.001). Technically; group (A) used only end to end arterial anastomosis as a standard technique, while group (B) used both end-to-end and end-to-side anastomoses as required per each case. End to side anastomosis in group (B) yielded better immediate graft response in the form of change in color, texture, earlier and more profuse postoperative urine volumes (P value 0.025). Furthermore, anastomosis to common and external iliac arteries (group B) yielded earlier and higher urine volumes than the internal iliac artery (P values 0.024 and 0.031 respectively). Group (B) recorded significantly less postoperative perigraft hematomas and lymphoceles compared to the other 2 groups. Equal rates of urine leaks, ICU stay, creatinine levels, patient and grafts survival rates among groups (A) and (B), while postoperative recovery and ICU stay duration were more lengthy in the complicated group (C). CONCLUSIONS A vascular surgeon operating in a transplantation team would deal comfortably and efficiently with various vascular related challenges and complications, thus avoiding unnecessary time waste, complications and costs.
Collapse
Affiliation(s)
- Ahmed M Kassem
- Vascular Surgery Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
| | - Ahmed F Al-Koraie
- Nephrology and Transplantation Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Wael E Shaalan
- Vascular Surgery Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ali A Elemam
- Vascular Surgery Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed O Korany
- Vascular Surgery Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
2
|
Serirodom M, Taweemonkongsap T, Chotikawanich E, Jitpraphai S, Woranisarakul V, Shrestha S, Hansomwong T. Lymphocele in Kidney Transplantation: A Comparison of Ligation and Non-ligation Technique of Iliac Lymphatic Dissection. Transplant Proc 2022; 54:2197-2204. [PMID: 36163083 DOI: 10.1016/j.transproceed.2022.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 07/03/2022] [Accepted: 07/14/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND To compare the incidence of lymphocele in kidney recipients following 2 lymphatic vessel division techniques: ligation and non-ligation. METHODS Retrospective reviews of the records of 402 patients with end-stage renal disease who underwent kidney transplantation from April 2015 to December 2019 at Siriraj Hospital. RESULTS Four hundred two patients were included in the study: 54.9% of the patients were male, and the patient's mean age was 41 years. There were 25.1% and 74.9% that received kidney grafts from living and deceased donors, respectively. The preoperative renal replacement therapies were 83.3% hemodialysis, 12.9% peritoneal dialysis, and 3.7% preemptive transplantation. Two hundred forty-nine patients received lymphatic division with the ligation technique and 153 patients received the non-ligation. Lymphoceles were found in 31 cases (7.7%). Lymphocele occurrence in the ligation group was lower than in the non-ligation group: 5.2% compared to 11.8% (P value = .017). There were 22.6% of lymphoceles that had a spontaneous resolution with no treatment. DISCUSSION The ligation of iliac lymphatic vessels during division reduced the incidence of lymphoceles non-ligation.
Collapse
Affiliation(s)
- M Serirodom
- Division of Urology, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - T Taweemonkongsap
- Division of Urology, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - E Chotikawanich
- Division of Urology, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - S Jitpraphai
- Division of Urology, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - V Woranisarakul
- Division of Urology, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - S Shrestha
- Department of Surgery, Pokhara Academy of Health Sciences, Nepal
| | - T Hansomwong
- Division of Urology, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| |
Collapse
|
|
3
|
Oomen L, Bootsma-Robroeks C, Cornelissen E, de Wall L, Feitz W. Pearls and Pitfalls in Pediatric Kidney Transplantation After 5 Decades. Front Pediatr 2022; 10:856630. [PMID: 35463874 PMCID: PMC9024248 DOI: 10.3389/fped.2022.856630] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/15/2022] [Indexed: 11/13/2022] Open
Abstract
Worldwide, over 1,300 pediatric kidney transplantations are performed every year. Since the first transplantation in 1959, healthcare has evolved dramatically. Pre-emptive transplantations with grafts from living donors have become more common. Despite a subsequent improvement in graft survival, there are still challenges to face. This study attempts to summarize how our understanding of pediatric kidney transplantation has developed and improved since its beginnings, whilst also highlighting those areas where future research should concentrate in order to help resolve as yet unanswered questions. Existing literature was compared to our own data of 411 single-center pediatric kidney transplantations between 1968 and 2020, in order to find discrepancies and allow identification of future challenges. Important issues for future care are innovations in immunosuppressive medication, improving medication adherence, careful donor selection with regard to characteristics of both donor and recipient, improvement of surgical techniques and increased attention for lower urinary tract dysfunction and voiding behavior in all patients.
Collapse
Affiliation(s)
- Loes Oomen
- Division of Pediatric Urology, Department of Urology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
| | - Charlotte Bootsma-Robroeks
- Department of Pediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
- Department of Pediatrics, Pediatric Nephrology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Elisabeth Cornelissen
- Department of Pediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
| | - Liesbeth de Wall
- Division of Pediatric Urology, Department of Urology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
| | - Wout Feitz
- Division of Pediatric Urology, Department of Urology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
| |
Collapse
|
|
4
|
Santiago Rubio J, Wojtowicz D, Amore MA, Iriarte G, Di Pietrantonio S. Giant Idiopathic Lymphocele 18 Years After Kidney Transplantation, Treated Using Lymphatic Embolization With Lipiodol: Report of a Rare Case. EXP CLIN TRANSPLANT 2021; 19:1099-1102. [PMID: 34641778 DOI: 10.6002/ect.2021.0226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Kidney transplant is the best therapeutic option for patients with end-stage kidney disease. However, kidney transplant is not exempt from postoperative complications. One of the most frequent urological complications is lymphocele, which can appearin up to 20% of patients. Lymphocele most often appears during the first month after surgery. However, its appearance after the first yearis completely infrequent. Here, we report a case of a giant idiopathic lymphocele 18 years after kidney transplant and its resolution with lymphatic embolization.The patient, a 34-year-old man who received a deceased-donor kidney transplant in 2002, had presented with no complications until the lymphocele was diagnosed. The lymphocele presented as a voluminous organ-compressing mass. A percutaneous drainage was placed, and 3600 cm3 of lymphatic fluidwere drained.Afterthat, 800 cm3 continued to leak every day. An intranodal lymphography and lymphatic embolization with Lipiodol Ultra-Fluide (Guerbet Australia) were performed, owing to the high amount of leakage. At 50 days after embolization, an ultrasonograph showed no fluid collections, so the percutaneous catheter was removed. In most patients, the treatment ofthe lymphocele after kidney transplant is frequently conservative. However,for patients whose situation cannot be resolved spontaneously, there are few therapeutic choices. As described here, intranodal lymphatic embolization is a mini-invasive option, with a success rate of up to 80%, and should be offered as the first approach.
Collapse
Affiliation(s)
- Juan Santiago Rubio
- >From the Servicio de Trasplante Renal, Hospital de Alta Complejidad en Red "El Cruce" Dr. Néstor Carlos Kirchner, Florencio Varela, Buenos Aires, Argentina
| | | | | | | | | |
Collapse
|
|
5
|
Analysis of Risk Factors and Long-Term Outcomes in Kidney Transplant Patients with Identified Lymphoceles. J Clin Med 2020; 9:jcm9092841. [PMID: 32887366 PMCID: PMC7563120 DOI: 10.3390/jcm9092841] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 08/24/2020] [Accepted: 08/29/2020] [Indexed: 11/22/2022] Open
Abstract
The collection of lymphatic fluids (lymphoceles) is a frequent adverse event following renal transplantation. A variety of surgical and medical factors has been linked to this entity, but reliable data on risk factors and long-term outcomes are lacking. This retrospective single-center study included 867 adult transplant recipients who received a kidney transplantation from 2006 to 2015. We evaluated for patient and graft survival, rejection episodes, or detectable donor-specific antibodies (dnDSA) in patients with identified lymphoceles in comparison to controls. We identified 305/867 (35.2%) patients with lymphocele formation, of whom 72/867 (8.3%) needed intervention. Multivariate analysis identified rejection episode as an independent risk factor (OR 1.61, CI 95% 1.17–2.21, p = 0.003) for lymphocele formation, while delayed graft function was independently associated with symptomatic lymphoceles (OR 1.9, CI 95% 1.16–3.12, p = 0.011). Interestingly, there was no difference in detectable dnDSA between groups with a similar graft and patient survival in all groups after 10 years. Lymphoceles frequently occur after transplantation and were found to be independently associated with rejection episodes, while symptomatic lymphoceles were associated with delayed graft function in our cohort. As both are inflammatory processes, they might play a causative role in the formation of lymphoceles. However, development or intervention of lymphoceles did not lead to impaired graft survival in the long-term.
Collapse
|
|
6
|
Pacovsky J, Hyspler R, Husek P, Navratil P, Brodak M. Colloid Osmotic Pressure Participates on the Post-transplant Lymphocele Pathogenesis. Transplant Proc 2018; 50:3422-3425. [PMID: 30577216 DOI: 10.1016/j.transproceed.2018.06.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 06/27/2018] [Indexed: 10/28/2022]
Abstract
The aim of the study was to evaluate the role of colloid osmotic pressure in post-transplant lymphocele pathogenesis. We have analyzed total plasmatic protein and albumin levels, and electrophoresis has been completed in blood samples before transplantation and in days 3 and 14 after transplantation in 50 patients with lymphocele (Lymphocele) and 198 patients without lymphocele (control), respectively. Colloid osmotic pressure (COP) was calculated according to the Hoefs formula. Statistically significant differences were confirmed in albumin levels (42.2 respectively 44.8 g/L) before transplantation (day 0); in total protein (52.5 resp. 55.5 g/L), in albumin (30.1 resp. 32.1 g/L), and COP (15.6 respectively 17.7 kPa) in day 3; and in total protein (52.8 resp. 58.9 g/L), in albumin (30.5 respectively 35.4 g/L), in COP (16.1 respectively 21.2 kPa) in day 14. A potentially critical albumin level was established in 44.1 g/L in the blood analyzed, but its sensitivity was only 62%. The main risk element for the lymphocele formation remains the surgeon's hand. We can proclaim the role of proteins and their COP in the post-transplant lymphocele formation as one of possible pathogenetic cofactors. It is responsible for the impaired mechanisms of the reabsorption the lymph back to the tissues. Better metabolic care could help to reduce incidence of this surgical complication.
Collapse
Affiliation(s)
- J Pacovsky
- Department of Urology, University Hospital, Hradec Kralove, Czech Republic; Faculty of Medicine in Hradec Kralove, Department of Surgery, Charles University, Hradec Kralove, Czech Republic.
| | - R Hyspler
- Department of Clinical Biochemistry and Diagnostics, University Hospital, Hradec Kralove, Czech Republic
| | - P Husek
- Department of Urology, University Hospital, Hradec Kralove, Czech Republic
| | - P Navratil
- Department of Urology, University Hospital, Hradec Kralove, Czech Republic; Faculty of Medicine in Hradec Kralove, Department of Surgery, Charles University, Hradec Kralove, Czech Republic
| | - M Brodak
- Department of Urology, University Hospital, Hradec Kralove, Czech Republic; Faculty of Medicine in Hradec Kralove, Department of Surgery, Charles University, Hradec Kralove, Czech Republic
| |
Collapse
|
|
7
|
Leal R, Pinto H, Alves R, Figueiredo A. Late spontaneous decapsulation of the kidney graft in a patient with hepatitis C and treated with sirolimus: possible pathophysiological association in a rare complication. BMJ Case Rep 2017; 2017:bcr-2016-218335. [PMID: 28100577 DOI: 10.1136/bcr-2016-218335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Late decapsulation with fluid collection is a rare complication of renal transplantation with deleterious effects on kidney function. Its physiopathology is unclear but there might be an association with mammalian target of rapamycin (m-TOR) inhibitors, especially in patients with chronic hepatitis C. We report a case of late spontaneous decapsulation 12 years after kidney transplant in a patient infected with hepatitis C under treatment with sirolimus. He underwent marsupialisation of the collection, sirolimus was converted to cyclosporine and hepatitis C treatment was performed with success. This is the first successful case report of late spontaneous decapsulation of the kidney graft in a patient with hepatitis C.
Collapse
Affiliation(s)
- Rita Leal
- Department of Nephrology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Helena Pinto
- Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Rui Alves
- Department of Nephrology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Universidade de Coimbra Faculdade de Medicina, Coimbra, Portugal
| | - Arnaldo Figueiredo
- Universidade de Coimbra Faculdade de Medicina, Coimbra, Portugal.,Department of Urology and Kidney Transplantation, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| |
Collapse
|
|
8
|
Terrace JD, Oniscu GC. Paediatric obesity and renal transplantation: current challenges and solutions. Pediatr Nephrol 2016; 31:555-62. [PMID: 26018121 DOI: 10.1007/s00467-015-3126-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Revised: 04/27/2015] [Accepted: 04/28/2015] [Indexed: 12/16/2022]
Abstract
The increased incidence of obesity in the paediatric population poses significant challenges to renal transplantation. Whilst the body mass index appears to be widely used as a measure of obesity in adults, there are no standardised definitions in the paediatric population, making comparative analyses difficult. In the paediatric transplant population, obesity is associated with an increased incidence of surgical complications, diabetes, hyperlipidaemia and cardiovascular morbidity, leading to diminished graft function and impacting patient and graft survival. Management of obesity in renal transplantation requires multiple interventions starting with life-style and behavioural modification combined with medical and possibly surgical therapies, representing a unique challenge in the childhood setting. In this review we discuss the current challenges of obesity and potential solutions in the setting of paediatric transplantation.
Collapse
Affiliation(s)
- John D Terrace
- Transplant Unit, The Royal Infirmary of Edinburgh, Little France Crescent, Old Dalkeith Road, Edinburgh, EH16 4SA, UK
| | - Gabriel C Oniscu
- Transplant Unit, The Royal Infirmary of Edinburgh, Little France Crescent, Old Dalkeith Road, Edinburgh, EH16 4SA, UK.
| |
Collapse
|
|
9
|
Ranghino A, Segoloni GP, Lasaponara F, Biancone L. Lymphatic disorders after renal transplantation: new insights for an old complication. Clin Kidney J 2015; 8:615-22. [PMID: 26413290 PMCID: PMC4581383 DOI: 10.1093/ckj/sfv064] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 06/29/2015] [Indexed: 12/29/2022] Open
Abstract
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.
Collapse
Affiliation(s)
- Andrea Ranghino
- Renal Transplantation Center 'A. Vercellone', Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences , Città della Salute e della Scienza Hospital and University of Torino , Torino , Italy
| | - Giuseppe Paolo Segoloni
- Renal Transplantation Center 'A. Vercellone', Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences , Città della Salute e della Scienza Hospital and University of Torino , Torino , Italy
| | - Fedele Lasaponara
- Division of Urology , Città della Salute e della Scienza Hospital , Torino , Italy
| | - Luigi Biancone
- Renal Transplantation Center 'A. Vercellone', Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences , Città della Salute e della Scienza Hospital and University of Torino , Torino , Italy
| |
Collapse
|
|
10
|
Stylianou K, Maragkaki E, Kokologiannakis G, Stratigis S, Vardaki E, Daphnis E. Refractory and massive lymphocele in a transplant patient with encapsulating peritoneal sclerosis treated with a single infusion of bleomycin: a case report. Transplant Proc 2013; 45:2831-3. [PMID: 24034060 DOI: 10.1016/j.transproceed.2013.02.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2012] [Revised: 01/02/2013] [Accepted: 02/16/2013] [Indexed: 10/26/2022]
Abstract
A 26-year-old Caucasian man developed a large lymphocele after living-related kidney transplantation necessitating repeated drainage of large volumes every other day owing to ureteral compression. An open laparotomy for internal drainage was unsuccessful because of severe encapsulating peritoneal sclerosis. Prolonged external drainage with a catheter was inefficient. Repeated fine-needle aspirations of large volumes were needed to maintain ureteral patency over a period of 4 months. Finally, a single instillation of bleomycin immediately and effectively treated the lympocele with no relapse over the following 5 years. The presence of encapsulating peritoneal sclerosis seemed to be an obstacle to surgical treatment.
Collapse
Affiliation(s)
- K Stylianou
- Nephrology Department, Heraklion University Hospital, Crete, Greece.
| | | | | | | | | | | |
Collapse
|
|
11
|
Kalluri HV, Hardinger KL. Current state of renal transplant immunosuppression: Present and future. World J Transplant 2012; 2:51-68. [PMID: 24175197 PMCID: PMC3782235 DOI: 10.5500/wjt.v2.i4.51] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Revised: 11/23/2011] [Accepted: 06/30/2012] [Indexed: 02/05/2023] Open
Abstract
For kidney transplant recipients, immunosuppression commonly consists of combination treatment with a calcineurin inhibitor, an antiproliferative agent and a corticosteroid. Many medical centers use a sequential immunosuppression regimen where an induction agent, either an anti-thymocyte globulin or interleukin-2 receptor antibody, is given at the time of transplantation to prevent early acute rejection which is then followed by a triple immunosuppressive maintenance regimen. Very low rejection rates have been achieved at many transplant centers using combinations of these agents in a variety of protocols. Yet, a large number of recipients suffer chronic allograft injury and adverse events associated with drug therapy. Regimens designed to limit or eliminate calcineurin inhibitors and/or corticosteroid use are actively being pursued. An ideal immunosuppressive regimen limits toxicity and prolongs the functional life of the graft. This article contains a critical analysis of clinical data on currently available immunosuppressive strategies and an overview of therapeutic moieties in development.
Collapse
Affiliation(s)
- Hari Varun Kalluri
- Hari Varun Kalluri, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15260, United States
| | | |
Collapse
|
|
12
|
Yang MH, Loong CC, Wu CW, Lui WY. Late spontaneous kidney graft decapsulation after administration of sirolimus in a recipient with chronic hepatitis B and C infection: a case report. Transplant Proc 2008; 40:2437-9. [PMID: 18790260 DOI: 10.1016/j.transproceed.2008.07.044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Late spontaneous kidney graft decapsulation with fluid collection is a rare condition with only a few cases reported in the literature. Common causes of renal allograft rupture include acute rejection, acute tubular necrosis, renal vein thrombosis, and trauma. Sirolimus related late spontaneous decapsulation has not been reported in the past. Interestingly, sirolimus may promote lymphocele formation in renal transplant recipients, including those presenting with chronic hepatitis B or C. Herein, we report a case of late spontaneous decapsulation with subcapsular hematoma formation developing 12 years after receipt of a cadaveric allograft. The patient was infected with both hepatitis B and C viruses. Cyclosporine was replaced by sirolimus for maintenance therapy because of chronic rejection and acute deterioration of renal function. He presented to the hospital at 9 months after sirolimus inception because of a sudden onset of pain and swelling over the kidney graft. Magnetic resonance imaging found the capsule to be stripped from the kidney by a collection of liquefied hematomas. A laparoscopic fenestration was performed by creation of a peritoneal window adjacent to the renal allograft. When patients have chronic hepatitis, tacrolimus might be a better choice than sirolimus.
Collapse
Affiliation(s)
- M-H Yang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan
| | | | | | | |
Collapse
|
|
13
|
Prospective Comparison of the Use of Sirolimus and Cyclosporine in Recipients of a Kidney From an Expanded Criteria Donor. Transplantation 2008; 85:486-90. [DOI: 10.1097/tp.0b013e318160d3c9] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
14
|
Huber S, Bruns CJ, Schmid G, Hermann PC, Conrad C, Niess H, Huss R, Graeb C, Jauch KW, Heeschen C, Guba M. Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis. Kidney Int 2007; 71:771-7. [PMID: 17299523 DOI: 10.1038/sj.ki.5002112] [Citation(s) in RCA: 156] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Lymphatic complications are common side effects of mammalian target of rapamycin (mTOR) inhibitor-based immunosuppression in kidney transplantation. Therefore, we investigated whether the mTOR inhibitor rapamycin, besides its known antihemangiogenic effect, also impedes regenerative lymphangiogenesis. In a murine skin flap model, rapamycin impaired recovery of lymphatic flow across surgical incisions resulting in prolonged wound edema in these animals. Importantly, the antilymphangiogenic effect of rapamycin was not related to a general inhibition of wound healing as demonstrated an in vivo Matrigeltrade mark lymphangiogenesis assay and a model of lymphangioma. Rapamycin concentrations as low as 1 ng/ml potently inhibited vascular endothelial growth factor (VEGF)-C driven proliferation and migration, respectively, of isolated human lymphatic endothelial cells (LECs) in vitro. Mechanistically, mTOR inhibition impairs downstream signaling of VEGF-A as well as VEGF-C via mTOR to the p70S6 kinase in LECs. In conclusion, we provide extensive experimental evidence for an antilymphangiogenic activity of mTOR inhibition suggesting that the early use of mTOR inhibitor following tissue injury should be avoided. Conversely, the antilymphangiogenic properties of rapamycin and its derivates may provide therapeutic value for the prevention and treatment of malignancies, respectively.
Collapse
Affiliation(s)
- S Huber
- Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Smyth GP, Beitz G, Eng MP, Gibbons N, Hickey DP, Little DM. Long-Term Outcome of Cadaveric Renal Transplant After Treatment of Symptomatic Lymphocele. J Urol 2006; 176:1069-72. [PMID: 16890692 DOI: 10.1016/j.juro.2006.04.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2005] [Indexed: 11/18/2022]
Abstract
PURPOSE Between January 1993 and December 2002 a total of 1,289 renal transplants were performed at our institution. Symptomatic post-transplant lymphocele presenting as increased creatinine and hydronephrosis of the allograft was recorded at 0.02%. Records of the 27 patients in whom symptomatic lymphocele developed and of those who underwent contralateral kidney transplant (control group) were compared to determine the long-term effects of lymphocele formation on allograft function. MATERIALS AND METHODS A total of 37 procedures for the treatment of lymphocele were performed in 24 patients. Open marsupialization (12) and laparoscopic marsupialization (3) procedures were performed as primary treatments. Two patients underwent repeat open marsupialization. Aspiration and percutaneous catheter drainage were performed as a primary procedure in 7 and 1 cases, respectively. Percutaneous nephrostomy was required in 4 cases before definitive treatment. RESULTS The mean time to development of a lymphocele was 121 days (range 35 to 631). Symptomatic lymphocele did not require treatment in 3 patients. Of 19 patients undergoing primary marsupialization, recurrence in 2 necessitated repeat surgery. However, aspiration and percutaneous drainage proved to be definitive in only 2 cases. In total 8 patients required more than 1 procedure. At a mean followup of 63 months (SD 30.3) 21 allografts continued to function with a mean serum creatinine of 152 mumol/l (SD 67.9). In the control group 3 patients experienced graft failure and mean serum creatinine was 154 mumol/l (SD 51.9). Five patients died in the lymphocele group, 2 with functioning grafts compared to 4 deaths in the control group. CONCLUSIONS Surgical marsupialization is the preferred primary treatment for symptomatic lymphocele and is associated with excellent long-term allograft outcome.
Collapse
Affiliation(s)
- G P Smyth
- Department of Urology and Transplantation, Beaumont Hospital, Dublin 9, Ireland
| | | | | | | | | | | |
Collapse
|
|
16
|
Abstract
Sirolimus (rapamycin) is a macrocyclic lactone isolated from a strain of Streptomyces hygroscopicus that inhibits the mammalian target of rapamycin (mTOR)-mediated signal-transduction pathways, resulting in the arrest of cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus has been demonstrated to prolong graft survival in various animal models of transplantation, ranging from rodents to primates for both heterotopic, as well as orthotopic organ grafting, bone marrow transplantation and islet cell grafting. In human clinical renal transplantation, sirolimus in combination with ciclosporin (cyclosporine) efficiently reduces the incidence of acute allograft rejection. Because of the synergistic effect of sirolimus on ciclosporin-induced nephrotoxicity, a prolonged combination of the two drugs inevitably leads to progressive irreversible renal allograft damage. Early elimination of calcineurin inhibitor therapy or complete avoidance of the latter by using sirolimus therapy is the optimal strategy for this drug. Prospective randomised phase II and III clinical studies have confirmed this approach, at least for recipients with a low to moderate immunological risk. For patients with a high immunological risk or recipients exposed to delayed graft function, sirolimus might not constitute the best therapeutic choice--despite its ability to enable calcineurin inhibitor sparing in the latter situation--because of its anti-proliferative effects on recovering renal tubular cells. Whether lower doses of sirolimus or a combination with a reduced dose of tacrolimus would be advantageous in these high risk situations remains to be determined. Clinically relevant adverse effects of sirolimus that require a specific therapeutic response or can potentially influence short- and long-term patient morbidity and mortality as well as graft survival include hypercholesterolaemia, hypertriglyceridaemia, infectious and non-infectious pneumonia, anaemia, lymphocele formation and impaired wound healing. These drug-related adverse effects are important determinants in the choice of a tailor-made immunosuppressive drug regimen that complies with the individual patient risk profile. Equally important in the latter decision is the lack of severe intrinsic nephrotoxicity associated with sirolimus and its advantageous effects on arterial hypertension, post-transplantation diabetes mellitus and esthetic changes induced by calcineurin inhibitors. Mild and transient thrombocytopenia, leukopenia, gastrointestinal adverse effects and mucosal ulcerations are all minor complications of sirolimus therapy that have less impact on the decision for choosing this drug as the basis for tailor-made immunosuppressive therapy. It is clear that sirolimus has gained a proper place in the present-day immunosuppressive armament used in renal transplantation and will contribute to the development of a tailor-made immunosuppressive therapy aimed at fulfilling the requirements outlined by the individual patient profile.
Collapse
Affiliation(s)
- Dirk R J Kuypers
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, University of Leuven, B-3000 Leuven, Belgium.
| |
Collapse
|
|
17
|
Hardinger KL, Koch MJ, Brennan DC. Current and future immunosuppressive strategies in renal transplantation. Pharmacotherapy 2004; 24:1159-76. [PMID: 15460177 DOI: 10.1592/phco.24.13.1159.38094] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The past decade has witnessed the introduction of several new immunosuppressive agents. The availability of these new pharmacologic offerings has not diminished the challenge of achieving a balance of adequate graft protection while minimizing the consequences of excessive immunosuppression. For renal transplant recipients, maintenance immunosuppression generally consists of a calcineurin inhibitor in combination with an antiproliferative agent and a corticosteroid; more recently, mammalian target of rapamycin inhibitors have been used. Excellent results have been achieved at many transplant centers with combinations of these agents in a variety of protocols. Regimens designed to limit or eliminate calcineurin inhibitor and/or corticosteroid therapy are actively being pursued in the transplant community. Allograft tolerance and xenotransplantation are being studied, and the knowledge gained from the effort may help in the development of innovative strategies and new immunosuppressive agents.
Collapse
Affiliation(s)
- Karen L Hardinger
- Department of Pharmacy, Barnes-Jewish Hospital, Washington University School of Medicine, St Louis, Missouri 63110, USA.
| | | | | |
Collapse
|
|
18
|
Why inhibitors of mammalian target of rapamycin will be important in organ transplantation. Curr Opin Organ Transplant 2004. [DOI: 10.1097/01.mot.0000146560.58398.e4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|