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Pancreas transplant (PTx) is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes types 1 and 2. The paper aims to review and analyze graft survival, patient survival, and the impact on diabetic complications. We describe that the graft survival was 82-98% at 1 year, 90% at 5 years, and 75-54% at 10 years for simultaneous pancreas-kidney recipient; 71% pancreas after kidney (PAK), and 62% PTx alone at 1 year. Patient survival: At 1 year for recipients was 96.9% simultaneous pancreas-kidney transplantation (SPK); for PAK transplantation recipients, 96.3%; and for PTx alone recipients, 98.3%. In general, the pancreas transplantation improves and reverses diabetic complications. Finally, the pancreatic transplant is a morbid procedure and emerges as a significant alternative in diabetes management, directly competing with conventional insulin therapies. Results so far suggest that the most effective transplant model is the SPK. While more patients could benefit from this procedure, surgical complications and the need for immunosuppression pose significant challenges.

El trasplante de páncreas es el único tratamiento que estabiliza los niveles normales de glucosa en los pacientes diagnosticados con diabetes tipo 1 o tipo 2. En esta revisión se analizan la supervivencia del injerto, la supervivencia del paciente y el impacto en las complicaciones diabéticas. Se describe la supervivencia del injerto: 82-98% al año para los receptores de trasplante simultáneo de páncreas y riñón, 71% para trasplante páncreas después de riñón y 62% para trasplante de páncreas solitario al año. Supervivencia de los pacientes a 1 año: 96.9% para los receptores de trasplante simultáneo de páncreas y riñón, 96.3% para los receptores de trasplante de páncreas después de riñón y 98.3% para los receptores de páncreas solitario. En general, el trasplante de páncreas mejora y revierte las complicaciones diabéticas. Finalmente, el trasplante de páncreas, un procedimiento mórbido, surge como una alternativa significativa en el manejo de la diabetes, compitiendo directamente con las terapias convencionales de insulina. Hasta ahora, los resultados indican que el modelo de trasplante más efectivo es el simultáneo de páncreas y riñón. Aunque más pacientes podrían beneficiarse de este procedimiento, las complicaciones quirúrgicas y la necesidad de inmunosupresión plantean desafíos significativos.

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INTRODUCTION: This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy. METHODS: A systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events. RESULTS: Thirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138). CONCLUSION: Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections.

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BACKGROUND: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.

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OBJECTIVE: To evaluate the etiology of and factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients. METHODS: This was a single-center case-control study conducted between December of 2017 and March of 2020 at a referral center for kidney transplantation in the city of Belo Horizonte, Brazil. The case:control ratio was 1:1.8. Cases included kidney or kidney-pancreas transplant recipients hospitalized with pulmonary infection. Controls included kidney or kidney-pancreas transplant recipients without pulmonary infection and matched to cases for sex, age group, and donor type (living or deceased). RESULTS: A total of 197 patients were included in the study. Of those, 70 were cases and 127 were controls. The mean age was 55 years (for cases) and 53 years (for controls), with a predominance of males. Corticosteroid use, bronchiectasis, and being overweight were associated with pulmonary infection risk in the multivariate logistic regression model. The most common etiologic agent of infection was cytomegalovirus (in 14.3% of the cases), followed by Mycobacterium tuberculosis (in 10%), Histoplasma capsulatum (in 7.1%), and Pseudomonas aeruginosa (in 7.1%). CONCLUSIONS: Corticosteroid use, bronchiectasis, and being overweight appear to be risk factors for pulmonary infection in kidney/kidney-pancreas transplant recipients, endemic mycoses being prevalent in this population. Appropriate planning and follow-up play an important role in identifying kidney and kidney-pancreas transplant recipients at risk of pulmonary infection.

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INTRODUCTION: Despite significant advancements in immunosuppressive regimens and surgical techniques, the prevalence of adverse events related to immunosuppression remains a major challenge affecting the long-term survival rates of pancreas and kidney allografts. AREAS COVERED: This article presents a comprehensive review of the literature and knowledge (Jan/2012-Feb/2023) concerning glucose metabolism disorders and nephrotoxicity associated with tacrolimus and mammalian target of rapamycin inhibitors (mTORi). Novel signaling pathways potentially implicated in these adverse events are discussed. Furthermore, we extensively examine the findings from clinical trials evaluating the efficacy and safety of tacrolimus, mTORi, and steroid minimization. EXPERT OPINION: Tacrolimus-based regimens continue to be the standard treatment following pancreas transplants. However, prolonged use of tacrolimus and mTORi may lead to hyperglycemia and nephrotoxicity. Understanding and interpreting experimental data, particularly concerning novel signaling pathways beyond calcineurin-NFAT and mTOR pathways, can offer valuable insights for therapeutic interventions to mitigate hyperglycemia and nephrotoxicity. Additionally, critically analyzing clinical trial results can identify opportunities for personalized safety-based approaches to minimize side effects. It is imperative to conduct randomized-controlled studies to assess the impact of mTORi use and steroid-free protocols on pancreatic allograft survival. Such studies will aid in tailoring treatment strategies for improved transplant outcomes.

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Background: Simultaneous pancreas-kidney transplantation (SPKT) is a complex and demanding procedure with a considerable risk of morbidity and mortality. Advances in surgical techniques and organ preservation have introduced changes in care protocols. Two cohorts of patients receiving SPKT with two different protocols were compared to determine overall survival and pancreatic and renal graft failure-free survival. Methods: This retrospective observational study was conducted in two cohorts of SPKT recipient patients that underwent surgery between 2001 and 2021. Outcomes were compared in transplant patients between 2001 and 2011 (cohort 1; initial protocol) and 2012-2021 (cohort 2; improved protocol). In addition to the temporality, the cohorts were defined by a protocolization of technical aspects and medical management in cohort 2 (improved protocol), compared to a wide variability in the procedures carried out in cohort 1 (initial protocol). Overall survival and pancreatic and renal graft failure-free survival were the primary outcomes. These outcomes were determined using Kaplan-Meier survival analysis and the log-rank test. Results: Fifty-five SPKT were performed during the study period: 32 in cohort 1 and 23 in cohort 2. In the survival analysis, an average of 2546 days (95% CI: 1902-3190) was found in cohort 1, while in cohort 2, it was 2540 days (95% CI: 2100-3204) (p > 0.05). Pancreatic graft failure-free survival had an average of 1705 days (95% CI: 1037-2373) in cohort 1, lower than the average in cohort 2 (2337 days; 95% CI: 1887-2788) (p = 0.016). Similarly, renal graft failure-free survival had an average of 2167 days (95% CI: 1485-2849) in cohort 1, lower than the average in cohort 2 (2583 days; 95% CI: 2159-3006) (p = 0.017). Conclusions: This analysis indicates that pancreatic and renal graft failure-free survival associated with SPKT decreased significantly in cohort 2, with results related to improvements in the treatment protocol implemented in that cohort.

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BACKGROUND: The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney-pancreas transplantation. METHODS: Retrospective data analysis from confirmed TB cases in adult kidney/kidney-pancreas transplant recipients (2006-2019), treated "de novo" with non-rifampin-containing regimens. RESULTS: Fifty-seven patients had confirmed TB. Thirty patients were treated "de novo" with non-rifampin-containing regimens. These patients' mean age was 49.24 (±11.50) years. Induction immunosuppression was used in 22 patients. Maintenance immunosuppression was tacrolimus-mycophenolate-steroids in 13 (43%), sirolimus-mycophenolate-steroids in 6 (20%), and other immunosuppressive regimens in 11 (36%). Belatacept was used in four patients. TB localizations: pulmonary 43%; disseminated 23%; extrapulmonary 33%. Twenty-seven (90%) patients completed treatment with isoniazid, ethambutol, and levofloxacin (12 months, 23; 9 months, 3; 6 months, 1); 12 of these patients also received pyrazinamide for the first 2 months and were cured with functioning grafts. One patient (3%) lost the graft while on treatment. Two patients (7%) died while on TB treatment. Median (range) follow-up after completion of TB treatment was 32 (8-150) months. No TB relapses were observed. CONCLUSIONS: Results with non-rifampin-containing TB treatments in this case series were better (in terms of mortality and graft dysfunction) than those previously described with rifampin-containing regimens in transplanted patients.

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PURPOSE: Simultaneous pancreas-kidney transplantation (SPKT) brings several benefits for insulin-dependent type-1 diabetic patients associated with end-stage renal disease (ESRD). However, data on psychological outcomes for the waiting list and the transplanted patients are still lacking. METHODS: Using the psychological Beck inventories of anxiety (BAI) and depression (BDI), 39 patients on the waiting list were compared to 88 post-transplanted patients who had undergone SPKT. RESULTS: Significant differences were found regarding depression (p = 0.003) but not anxiety (p = 0.161), being the pretransplant patients more vulnerable to psychological disorders. Remarkable differences were observed relative to the feeling of punishment (p < 0.001) and suicidal thoughts (p = 0.008) between the groups. It was observed that patients who waited a longer period for the transplant showed more post-transplant anxiety symptoms due to the long treatment burden (p = 0.002). CONCLUSIONS: These results demonstrated the positive impact of SPKT on psychological aspects related to depression when comparing the groups. The high number of stressors in the pretransplant stage impacts more severely the psychosocial condition of the patient.

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Purpose: Simultaneous pancreas-kidney transplantation (SPKT) brings several benefits for insulin-dependent type-1 diabetic patients associated with end-stage renal disease (ESRD). However, data on psychological outcomes for the waiting list and the transplanted patients are still lacking. Methods: Using the psychological Beck inventories of anxiety (BAI) and depression (BDI), 39 patients on the waiting list were compared to 88 post-transplanted patients who had undergone SPKT. Results: Significant differences were found regarding depression (p = 0.003) but not anxiety (p = 0.161), being the pretransplant patients more vulnerable to psychological disorders. Remarkable differences were observed relative to the feeling of punishment (p < 0.001) and suicidal thoughts (p = 0.008) between the groups. It was observed that patients who waited a longer period for the transplant showed more post-transplant anxiety symptoms due to the long treatment burden (p = 0.002). Conclusions: These results demonstrated the positive impact of SPKT on psychological aspects related to depression when comparing the groups. The high number of stressors in the pretransplant stage impacts more severely the psychosocial condition of the patient.

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