Late Conversion to Sirolimus or Everolimus After Pancreas Transplant.

BACKGROUND: Pancreas transplant is an effective treatment for insulin-dependent diabetic individuals with end-stage renal disease, yet immunosuppression-associated adverse events may adversely affect patient and graft survival. The aim of the study was to document whether mammalian target of rapamycin inhibitors (mTORi) are safe and effective as a second-line drug after pancreas transplant. METHODOLOGY: An observational single-center study was performed in a cohort of 490 simultaneous pancreas-kidney transplant and 45 pancreas-after-kidney transplant individuals after conversion to mTORi (n = 13) owing to adverse events of either tacrolimus or mycophenolate. RESULTS: mTORi conversion was performed 11.5 ± 10.1 (range, 1-28) months after pancreas transplant, mainly owing to cytomegalovirus infection and gastrointestinal intolerance. We frequently observed clinical complications after mTORi conversion, yet creatinine, eGFR, proteinuria, fasting plasma glucose, HbA1c, and C-peptide remained stable throughout the study (mean follow-up 8.2 ± 5, range 1-17) years, as did the lipid profile (P > .05). However, graft loss occurred in almost 20% of patients owing to chronic alterations. LIMITATIONS: The small number of patients and a single-center cohort were limitations of the study. CONCLUSIONS: Late mTORi conversion is a safe and effective approach when tacrolimus or mycophenolate-mediated adverse events occur after pancreas transplant.

The quality of life in type I diabetic patients with end-stage kidney disease before and after simultaneous pancreas-kidney transplantation: a single-center prospective study.

Simultaneous pancreas-kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end-stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life-Short-Form Health Survey (KDQOL-SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (<1, 1-3, and >3 years). Mean KDQOL-SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients' stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL.

Liver transplantation for carcinoma hepatocellular in Aão Paulo: 414 cases by the Milan/Brazil criteria / O transplante hepático por hepatocarcinoma na era meld em São Paulo: análise de 414 casos transplantados pelo critério de Milão/Brasil

ABSTRACT Background: The criterion of Milan (CM) has been used as standard for indication of liver transplantation (LTx) for hepatocellular carcinoma (HCC) worldwide for nearly 20 years. Several centers have adopted criteria expanded in order to increase the number of patients eligible to liver transplantation, while maintaining good survival rates. In Brazil, since 2006, the criterion of Milan/Brazil (CMB), which disregards nodules <2 cm, is adopted, including patients with a higher number of small nodules. Aim: To evaluate the outcome of liver transplantation within the CMB. Methods: The medical records of patients with HCC undergoing liver transplantation in relation to recurrence and survival by comparing CM and CMB, were analyzed. Results: 414 LTx for HCC, the survival at 1 and 5 years was 84.1 and 72.7%. Of these, 7% reached the CMB through downstaging, with survival at 1 and 5 years of 93.1 and 71.9%. The CMB patient group that exceeded the CM (8.6%) had a survival rate of 58.1% at five years. There was no statistical difference in survival between the groups CM, CMB and downstaging. Vascular invasion (p<0.001), higher nodule size (p=0.001) and number of nodules >2 cm (p=0.028) were associated with relapse. The age (p=0.001), female (p<0.001), real MELD (p<0.001), vascular invasion (p=0.045) and number of nodes >2 cm (p<0.014) were associated with worse survival. Conclusions: CMB increased by 8.6% indications of liver transplantation, and showed survival rates similar to CM.

RESUMO Racional: O critério de Milão (CM) vem sendo utilizado como padrão para indicação do transplante hepático (TxH) por hepatocarcinoma (HCC) em todo mundo há quase 20 anos. Diversos centros têm adotado critérios expandidos com intuito de aumentar o número de pacientes candidatos ao transplante, mantendo bons índices de sobrevida. No Brasil, desde 2006, o critério de Milão/Brasil (CMB), que desconsidera nódulos <2 cm, é adotado, incluindo pacientes com maior número de nódulos pequenos. Objetivo: Avaliar o resultado do transplante hepático dentro do CMB. Métodos: Foram analisados os prontuários dos pacientes com HCC submetidos ao TxH em relação à recidiva e sobrevida através da comparação entre CM e CMB. Resultados: Em 414 TxH por HCC, a sobrevida em 1 e 5 anos foi de 84,1 e 72,7%. Destes, 7% atingiram o CMB através de downstaging, com sobrevida em 1 e 5 anos de 93,1 e 71,9%. O grupo de pacientes do CMB que excederam o CM (8,6%) teve sobrevida de 58,1% em cinco anos. Não houve diferença estatística na sobrevida entre os grupos CM, CMB e downstaging. A invasão vascular (p<0,001), tamanho do maior nódulo (p=0,001) e número de nódulos >2 cm (p=0,028) associaram-se com recidiva. A idade (p=0,001), sexo feminino (p<0,001), MELD real (p<0,001), invasão vascular (p=0,045) e o número de nódulos >2 cm (p<0,014) estiveram associados com a piora na sobrevida. Conclusões: O CMB aumentou em 8,6% as indicações de TxH e apresentou índices de sobrevida semelhantes ao CM.

LIVER TRANSPLANTATION FOR CARCINOMA HEPATOCELLULAR IN SÃO PAULO: 414 CASES BY THE MILAN/BRAZIL CRITERIA.

Background: The criterion of Milan (CM) has been used as standard for indication of liver transplantation (LTx) for hepatocellular carcinoma (HCC) worldwide for nearly 20 years. Several centers have adopted criteria expanded in order to increase the number of patients eligible to liver transplantation, while maintaining good survival rates. In Brazil, since 2006, the criterion of Milan/Brazil (CMB), which disregards nodules <2 cm, is adopted, including patients with a higher number of small nodules. Aim: To evaluate the outcome of liver transplantation within the CMB. Methods: The medical records of patients with HCC undergoing liver transplantation in relation to recurrence and survival by comparing CM and CMB, were analyzed. Results: 414 LTx for HCC, the survival at 1 and 5 years was 84.1 and 72.7%. Of these, 7% reached the CMB through downstaging, with survival at 1 and 5 years of 93.1 and 71.9%. The CMB patient group that exceeded the CM (8.6%) had a survival rate of 58.1% at five years. There was no statistical difference in survival between the groups CM, CMB and downstaging. Vascular invasion (p<0.001), higher nodule size (p=0.001) and number of nodules >2 cm (p=0.028) were associated with relapse. The age (p=0.001), female (p<0.001), real MELD (p<0.001), vascular invasion (p=0.045) and number of nodes >2 cm (p<0.014) were associated with worse survival. Conclusions: CMB increased by 8.6% indications of liver transplantation, and showed survival rates similar to CM.

Racional: O critério de Milão (CM) vem sendo utilizado como padrão para indicação do transplante hepático (TxH) por hepatocarcinoma (HCC) em todo mundo há quase 20 anos. Diversos centros têm adotado critérios expandidos com intuito de aumentar o número de pacientes candidatos ao transplante, mantendo bons índices de sobrevida. No Brasil, desde 2006, o critério de Milão/Brasil (CMB), que desconsidera nódulos <2 cm, é adotado, incluindo pacientes com maior número de nódulos pequenos. Objetivo: Avaliar o resultado do transplante hepático dentro do CMB. Métodos: Foram analisados os prontuários dos pacientes com HCC submetidos ao TxH em relação à recidiva e sobrevida através da comparação entre CM e CMB. Resultados: Em 414 TxH por HCC, a sobrevida em 1 e 5 anos foi de 84,1 e 72,7%. Destes, 7% atingiram o CMB através de downstaging, com sobrevida em 1 e 5 anos de 93,1 e 71,9%. O grupo de pacientes do CMB que excederam o CM (8,6%) teve sobrevida de 58,1% em cinco anos. Não houve diferença estatística na sobrevida entre os grupos CM, CMB e downstaging. A invasão vascular (p<0,001), tamanho do maior nódulo (p=0,001) e número de nódulos >2 cm (p=0,028) associaram-se com recidiva. A idade (p=0,001), sexo feminino (p<0,001), MELD real (p<0,001), invasão vascular (p=0,045) e o número de nódulos >2 cm (p<0,014) estiveram associados com a piora na sobrevida. Conclusões: O CMB aumentou em 8,6% as indicações de TxH e apresentou índices de sobrevida semelhantes ao CM.

Charcot neuroarthropathy after simultaneous pancreas-kidney transplant.

BACKGROUND: Immunosuppressive regimen is associated with several metabolic adverse effects. Bone loss and fractures are frequent after transplantation and involve multifactorial mechanisms. METHODS: A retrospective analysis of 130 patients submitted to simultaneous pancreas-kidney transplantation (SPKT) and an identification of risk factors involved in de novo Charcot neuroarthropathy by multivariate analysis were used; P<0.05 was considered significant. RESULTS: Charcot neuroarthropathy was diagnosed in 4.6% of SPKT recipients during the first year. Cumulative glucocorticoid doses (daily dose plus methylprednisolone pulse) during the first 6 months both adjusted to body weight (>78 mg/kg) and not adjusted to body weight were associated with Charcot neuroarthropathy (P=0.001 and P<0.0001, respectively). Age, gender, race, time on dialysis, time of diabetes history, and posttransplantation hyperparathyroidism were not related to Charcot neuroarthropathy after SPKT. CONCLUSIONS: Glucocorticoids are the main risk factors for de novo Charcot neuroarthropathy after SPKT. Protocols including glucocorticoid avoidance or minimization should be considered.

Islet versus pancreas transplantation in Brazil: Defining criteria for pancreas allocation decision.

BACKGROUND: Many studies have evaluated whether there are characteristics related to pancreas donors and the islet isolation process that can influence pancreatic islet yield. However, this analysis has not yet been performed in Brazil, one of the world leaders in whole pancreas organ transplantation (WOPT), where pancreas allocation for pancreatic islet transplantation (PIT) has no officially defined criteria. Definition of parameters that would predict the outcome of islet isolation from local pancreas donors would be useful for defining allocation priority in Brazil. OBJECTIVE: To analyze the relationship between multiple donor-related and islet isolation variables with the total number of isolated pancreatic islet equivalents (IEQ) in a brazilian sample of pancreas donors. METHODS: Several variables were analyzed in 74 pancreata relative to the outcome of total IEQs obtained at the end of the process. RESULTS: In univariate analysis, body mass index (BMI) (p = 0.003), the presence of fatty infiltrates in the pancreas as observed during harvesting (p = 0.042) and pancreas digestion time (p = 0.046) were identified as variables related to a greater IEQ yield. In a multivariate analysis a statistically significant contribution to the variability of islet yield was found only for the BMI (p = 0.017). A ROC curve defined a BMI = 30 as a cut-off point, with pancreata from donors with BMI > 30 yielding more islets than donors with BMI < 30 (p< 0.001). CONCLUSION: These data reinforce the importance of the donor BMI as a defining parameter for successful islet isolation and establishes this variable as a potential pancreas allocation criterion in Brazil, where there is unequal competition for good quality organs between WOPT and PIT.

Family history of diabetes as a new determinant of insulin sensitivity and secretion in patients who have undergone a simultaneous pancreas-kidney transplant.

OBJECTIVES: We used homeostasis model assessment to investigate insulin sensitivity and secretion after a simultaneous pancreas-kidney transplant or kidney transplant alone. In that model, fasting plasma glucose and C-peptide levels are used to evaluate insulin sensitivity and beta-cell function. MATERIALS AND METHODS: Factors (eg, age, sex, race, delayed kidney allograft function) were correlated with homeostasis model assessment of beta-cell function and homeostasis model assessment of insulin sensitivity values after simultaneous pancreas-kidney transplant (n=89) or kidney transplant alone (n=68), and the results were compared with those in healthy subjects (n=49). RESULTS: Homeostasis model assessment of beta-cell function values were similar in patients who underwent kidney transplant alone or a simultaneous pancreas-kidney transplant, and were higher than homeostasis model assessment of beta cell function values in healthy subjects. The homeostasis model assessment of insulin sensitivity showed intermediate values for patients who underwent a simultaneous pancreas-kidney transplant and correlated with prednisone dosages (in those who underwent kidney transplant alone) and tacrolimus levels (in patients who underwent a simultaneous pancreas-kidney transplant). Homeostasis model assessment of beta-cell function values correlated with prednisone dosages in both groups and with tacrolimus levels in only those who underwent a simultaneous pancreas-kidney transplant. The body mass index of subjects who underwent kidney transplant alone correlated with both homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results. A family history of diabetes in subjects who underwent a simultaneous pancreas-kidney transplant correlated with homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results. CONCLUSIONS: Immunosuppressive regimen and body mass index were linked with reduced insulin sensitivity after kidney transplant. A family history of diabetes was linked with higher values of insulin secretion and lower insulin sensitivity in patients who underwent a simultaneous pancreas-kidney transplant.

The evolution of diabetic chronic complications after pancreas transplantation.

Pancreas transplantation is an invasive procedure that can restore and maintain normoglycemic level very successfully and for a prolonged period in DM1 patients. The procedure elevates the morbimortality rates in the first few months following the surgery if compared to kidney transplants with living donors, but it offers a better quality of life to patients.Although controversial, several studies have shown the stabilization or the improvement of some of the chronic complications related to diabetes, as well as the extra number of years of life that patients submitted to a double pancreas-kidney transplantation may gain.Recent studies have demonstrated clashing outcomes regarding isolated pancreas transplantations, a fact which reinforces the need for a more discerning selection of patients for this procedure.

Kidney transplant in diabetic patients: modalities, indications and results.

BACKGROUND: Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy. CONCLUSION: Type 1 and 2 diabetic patients present higher survival rates after transplant in comparison to the dialysis therapy, although the prevalence of cardiovascular events and infectious complications remain higher than in the general population.

O impacto da função do enxerto renal e da ocorrência de infecção intra-abdominal na sobrevida em 1 ano do paciente após o transplante simultâneo de pâncreas-rim (TSPR) / The impact of kidney function and intra-abdominal infection on patient 1-yr survival after simultaneous pancreas-kidney transplantation (SPKT)

O transplante de pâncreas-rim (TSPR) é um dos tratamentos mais efetivos para o paciente com diabetes melito e insuficiência renal crônica. Métodos: Foram realizadas análises retrospectivas da sobrevida de 150 pacientes submetidos ao TSPR pela regressão de COX e determinação das curvas de Kaplan-Meier, além das análises uni - e multivariadas para identificação dos fatores de risco tradicionais e aqueles relacionados ao transplante. Resultados: As taxas de sobrevidas em um ano dos pacientes, dos enxertos renais e pancreáticos foram de 82,0%, 80,0% e 76,7%, respectivamente. Função retardada do enxerto renal (FRR) (P = 0,001, RR 5,41), rejeição aguda renal (P = 0,016, RR 3,36) e infecção intra-abdominal (IIA) (P < 0,0001, RR 4,15) foram os principais fatores de risco que influenciaram a sobrevida do paciente em um ano. A sobrevida do paciente em um ano esteve relacionada à ocorrência de FRR (P = 0,013, RC 3,39), à rejeição aguda renal (P = 0,001, RC 4,74) e à IIA (P = 0,003, RC 6,29). A sobrevida do enxerto pancreático em um ano esteve relacionada à IIA (P < 0,0001, RC 12,83), à trombose vascular (P = 0,002, RC 40,55), à rejeição aguda renal (P = 0,027, RC 3,06), ao sódio do doador > 155 mEq/L (P = 0,02, RC 3,27) e ao uso de dopamina > 7,6 µcg/kg/min (P = 0,046, RC 2,85). Discussão: A ocorrência de função retardada do enxerto renal e infecção intraabdominal teve impacto na sobrevida em um ano tanto do paciente quanto dos enxertos renal e pancreático

Simultaneous pancreas-kidney transplantation (SPKT) is one of the treatments for insulin-dependent patients with chronic renal failure. Methods: One-year patient and kidney allograft survival rates of 150 patients submitted to SPKT analyzed by COX regression and Kaplan-Meier. Uni- and multivariate analysis identified the risk factors involved with either allograft or patient survival. Results: One-year patient and kidney allograft survival rates were 82% and 80%, respectively. Delayed graft function from kidney (DGF) (P = 0.001, HR 5.41), acute kidney rejection (P = 0.016, HR 3.36) and intra-abdominal infection (IAI) (P < 0.0001, HR 4.15) were related to the 1-yr patient survival. One-year kidney allograft survival was also related to DGF (P = 0.013, OR 3.39), acute rejection (P = 0.001, OR 4.74) and IAI (P = 0.003, OR 6.29). Main risk factors for DGF: time on dialysis > 27 months (P = 0.046, OR 2.59), kidney cold ischemia time > 14 hours (P = 0.027, OR 2.94), donor age > 25 years (P = 0.03, OR 2.82) and donor serum sodium > 155 mEq/l (P < 0.0001, OR 1.09). Conclusions: Delayed kidney allograft function and IAI had an important impact on either patient or kidney allograft survival rates. Improving deceased donor care may reduce DGF occurrence.

Impact of pancreatic allograft function on 1-year survival rates after simultaneous pancreatic-renal transplant.

OBJECTIVES: Simultaneous pancreatic-renal transplant is an effective treatment for insulin-dependent patients with chronic renal failure. We sought to identify the main influences on pancreatic and patient survival rates after simultaneous pancreas-kidney transplants. PATIENTS AND METHODS: The 1-year patient and pancreas survival rates of 150 patients who had undergone simultaneous pancreas-kidney transplant were analyzed by the Cox proportional hazards regression model and the Kaplan-Meier method. Uni and multivariate analyses were performed in terms of transplant-, recipient-, and donor-related risk factors. RESULTS: At 1 year, patient and pancreatic allograft survival rates were 82% and 76.7%, respectively. Delayed graft function in the kidney (P = .001, HR 5.41), acute kidney rejection (P = .016, HR 3.36), and intra-abdominal infection (P < .0001, HR 4.15) were the main factors related to 1-year patient survival. Pancreatic allograft survival at 1 year was related to intra-abdominal infection (P < .0001, OR 12.83), vascular thrombosis (P = .002, OR 40.55), acute kidney rejection (P = .027, OR 3.06), donor sodium greater than 155 mEq/L (P = .02, OR 3.27), and dopamine administration exceeding 7.6 microg/kg/min (P = .046, OR 2.85). CONCLUSIONS: Delayed kidney allograft function and intra-abdominal infection had an important effect on both patient and pancreatic allograft survival rates.

Thrombotic microangiopathy after simultaneous pancreas-kidney transplantation.

Thrombotic microangiopathy (TMA) is rare after transplantation and is associated with a high incidence of kidney graft dysfunction. Between December 2000 and March 2006, 136 simultaneous pancreas-kidney transplantations were performed with an incidence of TMA of 5.1% (71.4% localized to kidney allograft). All cases were diagnosed during the first three months and were attributed to tacrolimus; 74% were women. Systemic TMA presented higher values of lactate dehydrogenase (2658 +/- 659 U/L vs. 1331 +/- 473 U/L, p = 0.04) and a greater decrease in hematocrit (45.8 +/- 17.7% vs. 19.2 +/- 6%, p = 0.02) than in localized TMA. Acute kidney rejection complicated almost 90% of the cases with 43% of kidney graft lost. Tacrolimus was switched to sirolimus and fresh-frozen plasma was administered. Creatinine clearance after a mean follow-up of two yr was 100.7 mL/min/1.73 m(2) and 57.9 mL/min/1.73 m(2) in patients with systemic and localized TMA, respectively. In conclusion, sirolimus is an alternative to TMA associated with tacrolimus.

Effects of Eurocollins solution as aortic flush for the procurement of human pancreas.

BACKGROUND: Belzer solution is considered to be the best preservation media used for pancreas transplantation; however, its high cost accounts for approximately 14.5% of all resources allocated by the Brazilian government toward each pancreatic transplant. The objective of the present study was to test a reduction of Belzer solution during pancreas harvest, thereby lowering procedural cost. METHODS: The patients received pancreas-kidney transplantations during the period from January 2003 to August 2004. Patients were divided into two groups. Patients assigned to Group A (n=30) received only Belzer solution (2 L through the aorta artery), whereas patients in Group B (n=16) were perfused first with 1 L of Eurocollins solution followed by 1 L of Belzer solution. The two groups were assessed for differences in the following clinical parameters: the need for insulin replacement or antifungal and anticytomegalovirus treatment, pancreatitis, acute cellular rejection, graft vascular thrombosis, fistulas, intra-abdominal collection, graft loss, deaths, pancreatic ischemia time, and average hospitalization time. RESULTS: No statistically significant differences were observed in any of the parameters analyzed (P<0.05). The use of Eurocollins solution, followed by Belzer solution during pancreas harvesting, did not result in differences in graft survival or functionality, postsurgical complications, or patient survival and hospitalization time, when compared to the use of Belzer solution alone. CONCLUSIONS: Perfusion with 1 L of Eurocollins solution followed by 1 L of Belzer solution during pancreas harvesting seems to be a simple and efficient alternative for reducing the costs of the harvesting process.