Kidney Transplantation in the Obese Transplant Candidates: To Transplant or Not To Transplant?

The prevalence of obesity (body mass index ≥30 kg/m²) at the time of transplantation among kidney transplant recipients in the United States has doubled between 1987 and 2001 and continues to increase inexorably. Single‐center and large registry studies in kidney transplant recipients demonstrated that high body mass index (BMI) at transplant is associated with increased risk of wound and surgical site infections, delayed graft function (DGF), acute rejection episodes, and graft loss, among others. Hence, in many centers, obese transplant candidates are denied a transplant based on their body mass index (BMI) alone. The impact of obesity on short‐ and long‐term graft and patient outcomes after kidney transplantation are herein revisited, followed by the authors' proposed approach to evaluate and select obese transplant candidates for a kidney transplant. Suggested interventions to optimize the health of such candidates are also discussed.     

Abdominal Transplant Surgery and Transplant Coordination University Hospitals Leuven 1997–2007: an Overview

The transplant surgery and transplant coordination department was created in 1997 to meet up with the demand of the growing abdominal transplant surgery and organ procurement activity at the University Hospitals in Leuven. Since then, the procurement activity has increased and is currently distributed within the University Hospital Gasthuisberg and a network of ~25 collaborative hospitals. The profile of the donors has changed with older donors and more co-morbidity factors (obesity, hypertension, etc.). This donor activity represents ~30% of the national donor pool. Over the last 10 years, more than 1100 kidneys, more than 500 livers, ~50 pancreas, and 5 intestines have been transplanted in both adults and children. One year survival equal to-or exceeding 90% has been achieved for all abdominal organs and this compares favorably with international registries. More than 40 multi-visceral transplants {liver in combination with abdominal (kidney, pancreas, intestine) or thoracic (heart, double lung, heart-lung) organs} have been performed with results equivalent to isolated liver transplants and very little immunological graft loss (probably due to the immunoprotective effect of the liver). A live donation program was started for the kidney (40 cases) and for the liver (10 cases) in adults and children and no surgical graft loss has been seen so far. Introduction of new machine perfusion systems (and development of donor protocols) has made it possible to restart a non-heart-beating donor program for kidney transplantation. Experimental demonstration that livers tolerate short periods of warm ischemia has also allowed to start liver transplantation from non-heart-beating donors. In the future, machine perfusion of livers, viability testing, and biological modulation are likely to widen the use of marginal livers for transplantation and improve the results. An immunomodulatory protocol proven in the lab to induce the development of regulatory T cells has been applied clinically to 5 consecutive intestinal transplants. All 5 - at the time of writing - have been rejection-free and have achieved nutritional independence. Continuous research and development is warranted to increase the organ donor pool (currently the solely limiting factor of transplantation) and to optimize long-term graft and patient outcome.     

Kidney Transplant Recipients With Rheumatic Diseases: Epidemiological Data From the Polish Transplant Registries 1998–2015

Chronic kidney disease (CKD) is a common complication of rheumatic disorders. We analyzed the incidence of different rheumatic conditions as a primary diagnosis of end-stage renal disease (ESRD) in kidney transplant recipients in Poland.Data were received from the national waiting list for organ transplantation (Poltransplant) registries. Primary diagnosis leading to ESRD were analyzed in 15,984 patients who received kidney transplants between 1998 and 2015. There was no information about primary diagnosis in 4981 cases (31%) and in 1482 cases (9%) the diagnosis was described as unknown.Rheumatic diseases were specified in 566 (5.14%) kidney transplant recipients: lupus erythematosus, (systemic lupus erythematous nephritis) in 211 (1.92%), vasculitis in 176 (1.60%), amyloidosis AA in 82 (0.75%), hemolytic uremic syndrome in 59 (0.54%), secondary glomerulonephritis in 24 (0.22%), scleroderma in 9 (0.08%), rheumatoid arthritis in 4 (0.04%) and Sjögren syndrome in 1 (0.01%). Graft survival at 1 and 5 years were significantly better in the nonrheumatic versus rheumatic group (90 vs 87% and 76 vs 72% respectively, P = .04). Recipient survival at 5 years was significantly better in the nonrheumatic versus the rheumatic group (88 vs 84%, P = .02).Our study showed that systemic lupus erythematosus and systemic vasculitides are the major rheumatic causes of ESRD in the Polish population. Long-term graft and recipient survival were significantly better in the nonrheumatic versus the rheumatic group in the Poltransplant cohort.     

What Defines a Transplant Surgeon? A Needs Assessment for Curricular Development in Transplant Surgery Fellowship Training

This study compares the perceptions of transplant surgery program directors (PDs) and recent fellowship graduates (RFs) regarding the adequacy of training and relevancy to practice of specific curricular content items in fellowship training. Surveys were sent to all American Society of Transplant Surgery approved fellowship PDs and all RFs in practice <5 years. For operative procedures, the RFs considered the overall training to be less adequate than the PDs (p = 0.0117), while both groups considered the procedures listed to be relevant to practice (p = 0.8281). Regarding nonoperative patient care items, although RFs tended to rank many individual items lower, both groups generally agreed that the training was both adequate and relevant. For nonpatient care related items (i.e. transplant‐related ethics, economics, research, etc.), both groups scored them low regarding their adequacy of training although RFs scored them significantly lower than PDs (p = 0.0006). Regarding their relevance to practice, while both groups considered these items relevant, RFs generally considered them more relevant than PDs. Therefore, although there is consensus on many items, significant differences exist between PDs and RFs regarding their perceptions of the adequacy of training and the relevance to practice of specific curriculum items in transplant surgery fellowship training.     

Transplant tourism – a dangerous journey?

Polcari AJ, Hugen CM, Farooq AV, Holt DR, Hou SH, Milner JE. Transplant tourism – a dangerous journey?
Clin Transplant 2011: 25: 633–637. © 2010 John Wiley & Sons A/S. Abstract: Introduction: While the ethical aspects of transplant tourism have received much attention recently, less has been written about the medical safety of this practice. We retrospectively evaluated the outcomes of patients who purchased organs internationally and presented to our center for follow‐up care. Methods: Baseline demographic characteristics were recorded. Post‐operative outcomes including patient survival, graft survival, five‐yr graft function, and complications were assessed. Results: Eight patients who purchased international organs for transplant were identified. The country of transplant was China (n = 3), Pakistan (n = 3), India (n = 1), and the Philippines (n = 1). All patients were born in either Asia or the Middle East and traveled to the region of their ethnicity for transplantation. The mean time to presentation was 49 d post‐operatively. The overall one‐ and two‐yr patient survival rates were 87% and 75%, respectively. One patient died of miliary tuberculosis and another of Acinetobacter baumanii sepsis. There was one case of newly acquired hepatitis B infection. At last follow‐up, all six surviving patients had functioning grafts with a mean creatinine level of 1.26 mg/dL at five yr. Conclusion: Although intermediate‐term graft function is acceptable, the early morbidity and mortality among transplant tourists is high. These results suggest that the associated risks may not justify the trip.     

The Failed Renal Transplant: In or Out?

With the increased number of renal transplants being performed in the United States, there are also increasing numbers of early and long-term allograft failures. Patients with failed allografts require reentry into the end-stage renal disease (ESRD) system. If an allograft is producing little in the way of morbidity, it seems reasonable to continue the patient on low-dose immunosuppressive therapy to avoid sensitization while leaving the allograft in. This is particularly true if the allograft is providing enough renal function to keep the patient off dialysis. However, if the patient is having serious morbidity that may be due to the retained, failed kidney transplant, it may be necessary to remove the allograft kidney, which often shows ongoing inflammation. This may restore erythropoietin responsiveness and contribute to the overall benefit of the patient. The optimal protocol for withdrawal of immunosuppression in this circumstance has not been established by any scientific studies, and the effect of allograft nephrectomy on sensitization status and the ability to receive a crossmatch-negative retransplant are controversial. The author's personal approach is presented.     

γδT Cells Are Involved in Liver Transplant Tolerance

The role of nonconventional T cells in innate and adaptive immunity is just emerging; γδT cells play important roles in anti-tumor and anti-infectious diseases. The involvement of γδT cells in immunologic responses to hematopoietic cell transplantation remains controversial; divergent results have been reported depending on the murine strains and model systems. Whether γδT cells are involved in solid organ transplantation is understudied. We have characterized the γδT cells in mouse livers and spleens to evaluate their contributions to liver transplant tolerance posttransplantation using a murine allogeneic liver transplant model which induces spontaneous T regulatory cell (Treg)-dependent tolerance. Our studies revealed that γδT cells comprised about 20% of the population of liver nonparenchymal cells (NPCs). In naïve C3H mice they were CD4, CD8, and NK1.1 negative. The percentage of γδT cells decreased in spontaneously tolerated liver grafts posttransplantation from 20% in naïve C3H livers to <10% in allografts throughout the time course. In contrast, they increased in liver grafts with rejection induced by anti-CTLA4 plus anti-CD25 mAb administration. CD4 and CD8 expression on γδT cells dramatically increased in the tolerated but not rejected livers posttransplantation to >20% of CD4⁺ and 30% of CD8⁺. Our results suggested that γδT cells are involved in allogeneic immune responses. Whether γδT cells function as the causal or the effector cells in allograft tolerance rejection warrants further investigation.     

Transplant surgeons in training: is anybody out there?

There is a long-standing recognition that there is an organ donor shortage in the United Kingdom and Ireland (UK&E) that limits transplant activity. However, the fact that, at present, there are several unfilled consultant vacancies would suggest that a shortage of trained surgeons may soon be an equally important limiting factor. The aim of this current study was to identify all transplant trainees in the UK&E and to determine their career aspirations. A list of all trainees intending to practice as transplant surgeons was compiled. A combination of postal questionnaire and telephone interview was used to construct a database on past and present training in transplantation, and preferred type of consultancy was assessed both by direct questioning and by using a visual analogue scale to grade desirability of various posts. Of 110 potential trainees identified, 50 (45%) replied and indicated a desire to pursue a career in transplant surgery. Thirty-one intended practising in the UK&E (19 UK&E graduates and 12 overseas). The preferred consultancy (27/31) was transplantation (Tx) together with a second specialty while only four wanted a multivisceral practice. The mean score (0-10) for desirability of a multivisceral transplant post was 4.7, for renal transplant and vascular access it was 3.6 and for transplantation and a second specialty it was 8.4. We conclude that the majority of trainees do not wish to apply for pure transplant posts, either single organ or multivisceral, and that the majority wish to practice transplantation with a second specialty. In addition, there is still a major shortage of trainees and further studies are required to identify reasons why trainees fail to pursue a career in transplantation.     

Sildenafil Monotherapy to Treat Portopulmonary Hypertension Before Liver Transplant

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Patients with severe PPHTN are contraindicated for liver transplant because of the associated risk of intraoperative acute right heart failure during reperfusion phase or massive volume infusion. Therefore, it has been recommended that patients with moderate to severe PPHTN undergo medical treatment to lower the pulmonary artery pressure before undergoing transplant. Herein, we report 3 patients with severe PPHTN who underwent sildenafil monotherapy before living donor liver transplant. None of the patients experienced associated adverse effects during sildenafil treatment, and the pulmonary artery pressure was effectively reduced before transplant. The first patient was diagnosed during anesthesia prior to transplant, and the mean pulmonary artery pressure was reduced by 34% after treatment. The second and third patients were followed-up with echography, and the estimated pulmonary artery systolic pressure were reduced by 34% and 47%, respectively. Pretransplant right heart catheterization also confirmed the reduction of the mean pulmonary artery pressure. Intraoperative hemodynamic parameters were stable, and the 3 patients were discharged uneventfully. After transplant, sildenafil was discontinued, and all patients remained in a stable clinical and functional status during follow-up.     

How Do Hepatologists Gain Access to Liver Transplant Units?

Liver transplantation has evolved from an experimental treatment to be considered as the most effective therapy for end-stage liver disease and selected cases of hepatocellular carcinoma. Transplant hepatologists must have specific knowledge and abilities to treat those patients who receive a liver transplant. In Spain, approximately 1100 liver transplants are performed each year, and most centers assume both postoperative care and long-term follow-up, which has led to a significant work load in liver transplant units. Despite previous attempts to establish an official training program in hepatology, the Spanish health system does not presently have a specific liver transplant training program to guarantee that future needs of physicians are covered. Collaboration between health authorities and scientific societies is required to guarantee adequate assistance to liver transplant recipients in the future.     

Treatment of Immunoglobulin A Nephropathy Recurrence Post–Renal Transplant

Immunoglobulin A nephropathy (IgAN) is the most commonly occurring glomerulonephritis. Recurrence of disease in the transplanted kidney can significantly reduce allograft survival rates. Currently, there is no definitive management plan for IgAN recurrence in a transplant that reduces the rate of decline of allograft function and prolongs time to dialysis or re-transplantation. Herein we present a 48-year-old man who had received a renal transplantation in 2006 following his diagnosis of IgAN. In 2015, the patient was noted to have an elevated blood pressure and proteinuria (urinary protein:creatinine ratio [uPCR] 170 mg/mmol). A transplant biopsy confirmed recurrent IgAN. A year later, he presented with dipstick hematuria, nephrotic-range proteinuria (uPCR 820 mg/mmol), and a serum creatinine of 90 to 140 μmol/L. A second biopsy revealed mesangioproliferative glomerulopathy consistent with crescentic IgAN. An optimal management plan is currently unknown for recurrent crescentic IgAN in the transplanted kidney. We decided to treat this patient with oral cyclophosphamide daily and high-dose prednisolone. The treatment has so far yielded a positive response and managed to preserve allograft function without significant adverse effects for our patient. Our case illustrates the importance of timely biopsies to identify recurrence of disease and highlights an effective therapeutic option for recurrent IgAN with crescent formation in a transplant.     

Transforming Growth Factor-β1 Gene Polymorphism in Renal Transplant Recipients

Background. Cytokine transforming growth factor (TGF) is involved in regulation of tissue repair after injury. More recently, TGF–β1 codon 10 gene polymorphism has been shown to be associated with circulating TGF-β levels. We tested whether TGF-β1 genotype polymorphism was predictive of renal allograft function decline. Patients and Methods. The study population consisted of 129 consecutive cadaveric or living related renal transplant recipients at our center between 1985 and 2001. The recipient TGF-β1 genotype polymorphism was determined from peripheral blood leucocytes DNA. The primary endpoint was rate of glomerular filtration rate decline between the first year and the third year of transplant. Results. Baseline glomerular filtration rate as estimated by MDRD study equation at 1 year measured 50 ± 17 mL/min/1.73 m². At the end of the 3-year follow-up period, 52 patients (40%) experienced biopsy-confirmed acute rejections. Frequency and severity of allograft rejection did not differ with TGF-β genotypes. However, the decline in glomerular filtration rate was significantly greater in Leu/Leu (TT) than Leu/Pro (CT) recipients, 6.3 ± 16.9 mL/min/1.73 m² versus 0.1±10.2 mL/min/1.73 m², p = 0.04. Conclusion. Our results demonstrate that recipient TGF-β1 codon 10 Leu/Leu homozygosity is a potential risk factor of kidney allograft function decline.