Bariatric surgery in prospective obese living kidney donors: scoping review and management decision algorithm.

INTRODUCTION: Global chronic kidney disease is now epidemic, with substantial health and economic consequences. While scientific support for living donor renal transplants (LDRT) is strong, donor shortages necessitate consideration of expanded criteria, including obese individuals. Bariatric surgery (BS) may mitigate obesity-related risks, but research on living donor candidates is scarce. Our scoping review aims to compile evidence, identify gaps, and formulate an algorithm to guide healthcare professionals in evaluating BS for obese living donors. EVIDENCE ACQUISITION: We did a systematic search of studies on living kidney donors and obesity. We searched the MEDLINE Ovid, Embase Ovid, CENTRAL and Web of Science databases for studies from database inception to March 30, 2023. All English-language articles available in full text have been considered. Excluded are commentaries, editorials, letters, and abstracts. EVIDENCE SYNTHESIS: Obesity in LDRT raises long-term ESRD risk. Current high BMI donor admission raises ethical and clinical concerns. Encouraging timely weight loss can make obese candidates suitable donors, reducing risks. Sleeve gastrectomy is the most reported and preferable approach, since it minimizes hyperoxaluria risk. Re-evaluation for donation is possible 6-12 months post-BS, with BMI<35 for three months. Cost-benefit analysis favors BS over nephrectomy in obese donors (cost-benefit ratio: 3.64) when graft survival is equal. CONCLUSIONS: BS shows promise with short-term effectiveness and potential long-term outcomes. However, it should not be perceived as a means to expand the donor pool but rather as a personalized approach to address obesity and improve individuals' health.

How to Structure a Successful Organ Donation and Transplantation System in Eight (Not So Easy) Steps: An Italian Case Study.

Valuable information can be obtained from a systematic evaluation of a successful national transplant program. This paper provides an overview of Italy's solid organ transplantation program which is coordinated by the National Transplant Network (Rete Nazionale Trapianti) and The National Transplant Center (Centro Nazionale Trapianti). The analysis is based on a system-level conceptual framework and identifies components of the Italian system that have contributed to improving rates of organ donation and transplantation. A narrative literature review was conducted and the findings were validated iteratively with input from subject matter experts. The results were organized into eight critical steps, including 1) generating legal definitions of living and deceased donation, 2) taking steps to ensure that altruistic donation and transplantation become part of the national culture and a point of pride, 3) seeking out existing examples of successful programs, 4) creating a situation in which it is easy to become a donor, 5) learning from mistakes, 6) working to diminish risk factors that lead to the need for organ donation, 7) increasing the rate of donations and transplantations via innovative strategies and policies, and 8) planning for a system that supports growth.

The antigen CD300e drives T cell inflammation in adipose tissue and elicits an antibody response predictive of the insulin sensitivity recovery in obese patients.

Obesity and insulin resistance (IR), the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation. Bariatric surgery leads to a considerable reduction in the adipose tissue mass and systemic inflammation along with a reduction of IR, with a whole-body metabolic improvement. However, a sizable portion of people experience an IR relapse within few years of remission.Numerous studies have attempted to explore the best clinical predictors of the improvement of insulin sensitivity and the maintenance of glucose homeostasis after bariatric surgery, but no simple fasting blood test has been found to be effective in predicting the short and long-term beneficial effects on glycaemia.With the present study, we investigated T-cell and antibody responses against CD300e, an antigen highly expressed in the adipose tissue of patients with obesity before the bariatric surgery-induced weight loss. We found both in fat tissue and in peripheral blood anti-CD300e-specific T helper 1 responses. Moreover, we evidenced in the sera of individuals with obesity an antibody response towards CD300e and revealed the existence of a significant correlation between the level of antibodies before surgery and the maintenance of glucose control after the intervention.

Immunosuppressive treatment and radiotherapy in kidney transplant patients: A systematic review.

BACKGROUND: Immunosuppression (IS) therapy may contribute to cancer development. Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections, in immunosuppression-related diseases, and in patients undergoing radiotherapy. The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy. AIM: To define if it is necessary reduce immunosuppression drugs during radiotherapy. METHODS: The literature search was based on three electronic databases (Pubmed, Scopus, and Web of Science) using selected keywords linked through the "AND" and "OR" Boolean operators to build specific strings for each electronic search engine. Two researchers independently screened the citations, and disagreement was resolved by discussion or through the intervention of a third author. The review was conducted and reported according to the PRISMA statement. Extracted data were narratively synthesized, and, where possible, frequencies, percentages, and ranges were calculated. RESULTS: The literature search resulted in 147 citations. After abstracts screening, 21 records were selected for full-text evaluation. Fifteen of these were excluded, leaving six papers considered suitable for analysis. There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors, as opposed to continuing maintenance IS, improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy. Only few retrospective studies on small cancer patient cohorts are available in this setting, but without comparison of different immunosuppression treatments. Even where immunosuppression therapy was described, patient survival seemed to be correlated only with cancer stage and type. CONCLUSION: The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy.

Immune-checkpoint inhibitors in renal transplanted patients affected by melanoma: a systematic review.

Kidney transplantation leads to an increased risk of cancer. Melanoma is one of the most frequent neoplasms in kidney transplant recipients. Transplanted patients were excluded from trials with checkpoint inhibitors in melanoma. The authors performed a systematic review regarding the use of anti-PD1 and anti-CTLA4 agents in renal transplanted patients with melanoma. Thirty-four cases were included (24 progressive disease, eight partial responses and one stable disease) but no complete response were reported. Fourteen graft rejections were observed, especially with anti-PD1 agent. The median time from the start of immune-checkpoint inhibitor and rejection was 21 days. Response rate was similar between patients with rejection and patients without rejection. The benefit of immune-checkpoint inhibitors versus the risk of allograft rejection should be carefully weighted for each patient. A multidisciplinary approach should be considered to discuss the most appropriate treatment for every case, given the aggressiveness of melanoma in these subsets of patients.

Management of the kidney transplant patient with Cancer: Report from a Multidisciplinary Consensus Conference.

INTRODUCTION: Cancer is the second most common cause of mortality and morbidity in Kidney Transplant Recipients (KTRs). Immunosuppression can influence the efficacy of cancer treatment and modification of the immunosuppressive regimen may restore anti-neoplastic immune responses improving oncologic prognosis. However, patients and transplant physicians are usually reluctant to modify immunosuppression, fearing rejection and potential graft loss. Due to the lack of extensive and recognised data supporting how to manage the immunosuppressive therapy in KTRs, in the context of immunotherapy, chemotherapy, radiotherapy and loco-regional treatments, a Consensus Conference was organised under the auspices of the European Society of Organ Transplantation and the Italian Society of Organ Transplantation. The conference involved a multidisciplinary group of transplant experts in the field across Europe. METHODS: The overall process included a) the formulation of 12 specific questions based on the PICO methodology, b) systematic literature review and summary for experts for each question, c) a two-day conference celebration and the collection of experts' agreements. The conference was articulated in three sessions: "Immunosuppressive therapy and immunotherapy", "Systemic therapy", "Integrated Therapy", while the final experts' agreement was collected with a televoting procedure and defined according to the majority criterion. RESULTS: Twenty-six European experts attended the conference and expressed their vote. A total of 14 statements were finally elaborated and voted. Strong agreement was found for ten statements, moderate agreement for two, moderate disagreement for one and uncertainty for the last one. CONCLUSIONS: The consensus statements provide guidance to transplant physicians caring for kidney transplant recipients with cancer and indicate key aspects that need to be addressed by future clinical research.

Image-Guided Thermal Ablation in De Novo Renal Tumor Arising in Kidney Allograft: 3-Year Follow-Up. A Case Report.

De novo tumors in renal allograft recipients are a severe complication during long-term follow-up after transplantation and may require transplantectomy. Herein we present a case of de novo renal tumor arising in the renal allograft, treated with the less invasive image-guided radiofrequency ablation (RFA) with long-term follow-up. A tumor was detected during the routine annual follow-up in a patient with good renal function who underwent renal transplantation in 1989. Computed tomography (CT) showed a mass in the allograft whose shape, vascularization, and density suggested the presence of a solid, malignant mass, located in the upper renal pole, that measured 17 mm. CT-guided RFA was performed successfully, and the outcome was verified by an immediate control CT after the intervention. No residual pathologic tissue, major bleeding, or damage to the adjacent parenchyma was evidenced. The patient was discharged with stable renal function. CT scan and ultrasound were performed 3, 6, 12, 18, 24, and 36 months after RFA. No signs of change in renal function, recurrence, neovascularization, or damage to the adjacent microcirculation were observed during the 3-year follow-up. In conclusion, percutaneous RFA of small renal tumors occurring in renal allografts can be considered a function-sparing, safe, and effective therapeutic option when difficult surgical removal may be anticipated. Our experience also supports the need for yearly renal allograft ultrasound follow-up for early identification of small neoplasm than can be treated less invasively.

Behavioral and demographic factors associated with occurrence of non-melanoma skin cancer in organ transplant recipients.

BACKGROUND: Non-melanoma skin cancers (NMSC) are the most common epithelial malignancies in organ transplantation recipients (OTRs). In Italy, incidence rates of post-transplantation NMSC are approximately 5% after 5 years and 10% after 10 years since organ transplantation. The objective was to describe risk factors associated with NMSC in a cohort of renal and liver transplant recipients, in a single-center longitudinal study. METHODS: Renal and liver transplant patients, who underwent transplantation between June 1985 and December 2015, were visited for the first time or followed-up in a dedicated outpatient clinic every six months until July 2016. RESULTS: We included 356 renal and 76 liver transplant patients. 108 OTRs (25.6%) presented 299 NMSC. 74 patients developed actinic keratosis (17.1%), 36 patients squamous cell carcinoma (8.5%), and 52 patients basal cell carcinoma (12.3%). Time from transplantation and kidney transplant were the main risk factors for NMSC. Higher incidences of all NMSC were observed in patients >60 years, males and smokers, while decreased incidences were detected in individuals with higher educational levels. Multiple logistic regression models confirmed that male gender (RR 3.3, P=0.001), cigarette smoking (RR 2.0, P=0.026), light eye color (RR 2.9, P=0.001) and family history of cancer (RR 1.8, P=0.042) were independently associated with NMSC. CONCLUSIONS: Dermatological follow-up is important in OTRs, due to the higher risk of tumors and mainly NMSC. Clinical and environmental factors, including cigarette smoking, are useful in characterizing OTR with higher risk of NMSC.

Living Kidney Donation in a Type 1 Dent's Disease Patient from His Mother.

INTRODUCTION: Dent's disease is a rare X-linked recessive disorder that manifests in childhood or early adulthood and can lead to end-stage renal disease (ESRD). It occurs in males, who are hemizygous. In patients who develop ESRD, a deceased donor kidney transplant cures the disease. Females are obligate carriers of the mutated gene, and some show a mild Dent's disease phenotype. There may be reason for concern when considering a female obligate carrier (i.e., the mother) for kidney donation because of the risk of kidney function deterioration. CASE PRESENTATION: We describe the first successful kidney transplantation involving a patient with type 1 Dent's disease and ESRD given a kidney by an obligate carrier of the gene mutation, his mother. CONCLUSIONS: After careful assessment of the female obligate carriers, intrafamilial kidney donation in Dent's disease type 1 is feasible. No deteriorating renal function in the donor was observed.

Intrinsic factor recognition promotes T helper 17/T helper 1 autoimmune gastric inflammation in patients with pernicious anemia.

The intrinsic factor is the major humoral autoantigen in pernicious anemia/autoimmune gastritis. Although many studies have examined the autoantibody response to intrinsic factor and H+,K+-ATPase, no information is available on possible pathogenic mechanisms mediated by intrinsic factor - specific gastric T cells. Aim of this study was to investigate intrinsic factor-specific T cells in the gastric mucosa of pernicious anemia patients and define their functional properties. For the first time we provide evidence that gastric mucosa of pernicious anemia patients harbour a high proportion (20%) of autoreactive activated CD4+ T-cell clones that specifically recognize intrinsic factor. Most of these clones (94%) showed a T helper 17 or T helper 1 profile. All intrinsic factor-specific clones produced tumor necrosis factor-α, interleukin-21 and provided substantial help for B-cell immunoglobulin production. Most mucosa-derived intrinsic factor-specific T-cell clones expressed cytotoxicity against target cells. Our results indicate that activation of intrinsic factor-specific T helper 17 and T helper 1 T cells in the gastric mucosa represent a key effector mechanism in pernicious anemia suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Radiofrequency thermal ablation of renal graft neoplasms: A literature review.

Neoplasms occurring in renal grafts represent a relatively novel and rare condition, whose treatment has not been standardized yet. Radiofrequency thermal ablation (RFA) of renal graft neoplasms is a nephron-sparing treatment, reported to be safe and effective. However, even in the RFA field, there is no procedural standardization. In this review of the literature, mostly composed by case reports and case series, we aim to assess efficacy and complication rates of RFA in the treatment of kidney graft neoplasms, and summarize the various procedural protocols found in the literature, using an easy-to-read point format. We performed a literature search in PubMed/MEDLINE with an overall description of 66 renal graft lesion treated with RFA, with a mean follow-up of 16.3 months (range 3-54.3). Technical success was achieved in all cases, with only one recurrence reported (1/66; 1.5%), occurring at 6-months follow-up. Complications occurred in 11 (11/66; 16.7%) patients. Based on literature review, RFA of renal graft neoplasms seems to be a feasible, safe, and effective treatment.

Interleukin-17/Interleukin-21 and Interferon-γ producing T cells specific for ß2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome.

Systemic lupus erythematosus is frequently associated with antiphospholipid syndrome. Patients with lupus-antiphospholipid syndrome are characterized by recurrent arterial/venous thrombosis, miscarriages, and persistent presence of autoantibodies against phospholipid-binding proteins, such as ß2-Glycoprotein I. We investigated the cytokine production induced by ß2-Glycoprotein I in activated T cells that infiltrate in vivo atherosclerotic lesions of lupus-antiphospholipid syndrome patients. We examined the helper function of ß2-Glycoprotein I-specific T cells for tissue factor production, as well as their cytolytic potential and their helper function for antibody production. Lupus-antiphospholipid syndrome patients harbor in vivo activated CD4+ T cells that recognize ß2-Glycoprotein I in atherosclerotic lesions. ß2-Glycoprotein I induces T-cell proliferation and expression of both Interleukin-17/Interleukin-21 and Interferon-γ in plaque-derived T-cell clones. ß2-Glycoprotein I-specific T cells display strong help for monocyte tissue factor production, and promote antibody production in autologous B cells. Moreover, plaque-derived ß2-Glycoprotein I-specific CD4+ T lymphocytes express both perforin-mediated and Fas/FasLigand-mediated-cytotoxicity. Altogether, our results indicate that ß2-Glycoprotein I is able to elicit a local Interleukin-17/Interleukin-21 and Interferon-γ inflammation in lupus-antiphospholipid syndrome patients that might lead, if unabated, to plaque instability and subsequent arterial thrombosis, suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Inferior Long-Term Outcomes for Kidney Transplant Recipients With an Immunologically Mediated Primary Renal Disease.

OBJECTIVES: Recurrent glomerulonephritis can negatively affect kidney allograft survival. However, how primary renal disease affects transplant outcomes in the new era of immunosuppression remains unclear. MATERIALS AND METHODS: We categorized 426 kidney transplant recipients (performed from 1996 to 2007) into 4 disease groups: (1) 99 recipients with biopsy-proven immunologically mediated kidney disease, (2) 40 recipients with urologic disease, (3) 67 recipients with polycystic kidney disease, and (4) 220 recipients with other causes of terminal renal failure/uncertain kidney disease. Long-term transplant outcomes were compared between groups at 1, 5, and 10 years of follow-up. RESULTS: Compared with the urologic, polycystic, and other diseases groups, the immunologic group showed significantly lower time of graft survival (9.5 ± 4 vs 8 ± 4 vs 8.5 ± 4 vs 7 ± 4 years, respectively) and estimated glomerular filtration rate (52.5 ± 32 vs 49 ± 22 vs 50 ± 32 vs 35.5 ± 30 mL/min; P < .05). Relative risk of 10-year graft loss for the immunologic group was 2.8 (95% confidence interval, 1.6-4.9). Recurrence rate was 12% in the immunologic group versus 1% and 0% in the other diseases and remaining groups (P < .05). The relative risk of 10-year graft loss for patients with recurrence was 2.7 (95% confidence interval, 1.2-6.3). Ten-year graft loss rates for patients with biopsy-proven acute rejection, chronic allograft nephropathy, and recurrent glomerulonephritis were 30%, 23%, and 42% (P < .05). For those with biopsy-proven recurrent glomerulonephritis, 10-year estimated glomerular filtration rate was significantly lower than for those with biopsy-proven acute rejection or chronic allograft nephropathy (14 ± 6 vs 18 ± 7 vs 30 ± 10 mL/min; P < .05). CONCLUSIONS: Kidney transplant recipients with immunologically mediated kidney diseases have inferior long-term allograft survival and function versus patients with other causes of renal failure. Recurrence represents the strongest risk factor for premature loss of function and transplant failure.

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.

Thymoglobuline plus basiliximab a mixed cocktail to start?

Recent results reported by Ciancio et al. have demonstrated the long term successful use of dual induction therapy in kidney transplant recipients. Our experience using an "induction cocktail", thymoglobuline plus basiliximab, started in 2007 and we have treated 235 patients through the past 10years. In our population, we used a combination of CNIs and MMF or mTORi as maintenance therapy. Our results in term of patient and graft survival, acute rejection rate, renal function and incidence of post-transplant lymphoproliferative disorder support the data reported by Ciancio. We believe that double induction therapy allows on one hand to delay the CNIs introduction, reducing delayed graft function, and on the other hand protects the patient while building the targeted drugs exposures, so reducing the incidence of acute rejection.

ß2 Glycoprotein I Recognition Drives Th1 Inflammation in Atherosclerotic Plaques of Patients with Primary Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is characterized by recurrent arterial/venous thrombosis and miscarriages in the persistent presence of autoantibodies against phospholipid-binding proteins (aPLs), such as ß2 glycoprotein I (ß2GPI). In addition to the aPL thrombophilic effect, arterial thrombosis was related to accelerated atherosclerosis in animal models; however, contrasting findings were reported in primary APS patients with regard to the increased number of plaques or abnormal arterial wall thickness. We investigated the cytokine production induced by ß2GPI in activated T cells that infiltrate in vivo atherosclerotic lesions of primary APS patients with atherothrombosis. We also examined the helper function of ß2GPI-specific T cells for monocyte matrix metalloproteinase-9 and tissue factor production, as well as their cytolytic potential and their helper function for Ab production. APS patients with atherothrombosis harbor in vivo-activated CD4+ T cells that recognize ß2GPI in atherothrombotic lesions. ß2GPI induces T cell proliferation and IFN-γ expression in plaque-derived T cell clones. ß2GPI-specific T cells display helper function for monocyte matrix metalloproteinase-9 and tissue factor production and promote Ig production in autologous B cells. Moreover, plaque-derived ß2GPI-specific CD4+ T lymphocytes express perforin-mediated and Fas/Fas ligand-mediated cytotoxicity. ß2GPI, and especially the DI domain, drive a local Th1 inflammatory response, with subsequent plaque instability that eventually favors atherothrombosis. This finding may explain the association between aPLs and arterial thrombosis, despite the lack of evidence of surrogate markers for atherosclerosis in primary APS.

Emotional management and quality of life in mother living versus multi-organ donor renal transplant recipients.

The aim of this study was to evaluate psychological differences and quality of life between kidney recipients from living (mother) and multi-organ donor. Overall, 40 patients who had undergone both living (mother) and multi-organ kidney transplantation 3-6 months before were asked to complete four self-report instruments: Toronto Alexithymia Scale, Short Form Health Survey, Regulatory Emotional Self-efficacy, and Attachment Style Questionnaire. A greater difficulty in emotional, social, and mental health functioning was found in recipients receiving kidney from mother living donor. Moreover, in these patients, higher levels of avoidant attachment dimensions were associated with a worse quality of life.

[Surgical overview on kidney and pancreas transplantation]. / Problemi chirurgici nel trapianto di rene e di pancreas - Position paper.

The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed.