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      Impacto da função retardada do enxerto pancreático no transplante simultâneo pâncreas-rim Translated title: Impact of delayed pancreatic graft function in simultaneous pancreas-kidney transplantation

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          Abstract

          OBJETIVO: O transplante pâncreas-rim é efetivo para pacientes com doença renal crônica terminal e diabetes mellitus insulino-dependente. A função retardada do enxerto pancreático é condição frequente exercendo impacto significativo nos resultados em curto prazo dos transplantes pâncreas-rim. O objetivo foi analisar o impacto da função retardada do enxerto pancreático no transplante pâncreas-rim. MÉTODOS: Análise retrospectiva de 180 receptores de transplante pâncreas-rim, incluindo dados demográficos dos doadores e dos receptores, a reatividade contra painel, a incidência de rejeição aguda e as sobrevidas do paciente e dos enxertos pancreático e renal. RESULTADOS: A incidência de função retardada do enxerto pancreático foi 11%. A idade do receptor superior a 45 anos apresentou associação com o risco de desenvolvimento de função retardada do enxerto pancreático (Razão de chances 2,26; p < 0,05). Os pacientes com função retardada do enxerto pancreático apresentaram maior incidência de rejeição aguda renal (47 versus 24%; p < 0,05), glicemia de jejum alterada (25 versus 5%; p < 0,05) e média de hemoglobina glicada (5,8 versus 5,4%; p < 0,05) ao final do primeiro ano de acompanhamento em relação aos pacientes sem função retardada do enxerto pancreático. Não houve diferenças estatisticamente significativas entre os grupos de pacientes com e sem função retardada do enxerto pancreático quanto à sobrevida do paciente (95 versus 88,7%; p = 0,38), do enxerto pancreático (90 versus 85,6%; p = 0,59) e do enxerto renal (90 versus 87,2%; p = 0,70), respectivamente, nesse mesmo período. CONCLUSÃO: A função retardada do enxerto pancreático não exerceu impacto significativo nos resultados em curto prazo dos transplantes pâncreas-rim desta casuística. Embora a função retardada do enxerto pancreático não tenha influenciado a sobrevida do enxerto pancreático ao final do primeiro ano após o transplante, contribuiu para a disfunção pancreática precoce, indicando maior necessidade de uso de insulina e hipoglicemiantes orais.

          Translated abstract

          OBJECTIVE: Simultaneous pancreas-kidney transplantation is an effective treatment for patients with type 1 diabetes melli>tus and end-stage chronic kidney disease. Delayed pancreatic graft function is a common and multifactor condition with significant impact in short-term outcome of simultaneous pancreas-kidney transplantations. The aim of this study was to analyze the impact of pancreatic delayed pancreatic graft function on simultaneous pancreas-kidney transplantation. METHODS: Donor and recipient's demographic data, percentage of panel reactivity, acute rejection incidence, and patient and grafts survivals were retrospectively analyzed in 180 SPKT performed between 2002 and 2007. RESULTS: The incidence of pancreatic delayed pancreatic graft function was 11%. Donors older than 45 years had significant risk of pancreatic delayed pancreatic graft function (OR 2.26; p < 0,05). Patients with pancreatic delayed pancreatic graft function had higher rates of acute renal rejection (47 versus 24%; p < 0.05), altered fasting plasma glucose (25 versus 5%; p < 0.05) and mean glycated hemoglobin (5.8 versus 5.4%; p < 0.05), than patients without pancreatic delayed pancreatic graft function at the end of the first year of follow up. There were no significant differences between patients with and without pancreatic delayed pancreatic graft function regarding patient survival (95 versus 88.7%; p = 0.38), pancreatic graft survival (90 versus 85.6%; p = 0.59) and renal graft survival (90 versus 87.2%; p = 0.70), respectively at the sample period of time. CONCLUSION: Pancreatic delayed pancreatic graft function had no significant impact in the short-term outcome of simultaneous pancreas-kidney transplantations. Although delayed pancreatic graft function had no impact on 1-year pancreas graft survival, it contributed to early pancreas graft dysfunction, as assessed by enhanced insulin and oral anti-diabetic drugs requirements.

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          Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.

          Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft-Gault equations. Comparison of estimated and measured GFR. 15 clinical centers participating in a randomized, controlled trial. 1628 patients with chronic kidney disease participating in the MDRD Study. Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate. Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft-Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m2 or greater. The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a separate study sample. The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates.
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            Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease.

            Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
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              Aging and insulin secretion.

              Glucose tolerance progressively declines with age, and there is a high prevalence of type 2 diabetes and postchallenge hyperglycemia in the older population. Age-related glucose intolerance in humans is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people. Under some conditions of hyperglycemic challenge, insulin levels are lower in older people, suggesting beta-cell dysfunction. When insulin sensitivity is controlled for, insulin secretory defects have been consistently demonstrated in aging humans. In addition, beta-cell sensitivity to incretin hormones may be decreased with advancing age. Impaired beta-cell compensation to age-related insulin resistance may predispose older people to develop postchallenge hyperglycemia and type 2 diabetes. An improved understanding of the metabolic alterations associated with aging is essential for the development of preventive and therapeutic interventions in this population at high risk for glucose intolerance.
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                Author and article information

                Journal
                jbn
                Brazilian Journal of Nephrology
                Braz. J. Nephrol.
                Sociedade Brasileira de Nefrologia (São Paulo, SP, Brazil )
                0101-2800
                2175-8239
                June 2011
                : 33
                : 2
                : 180-188
                Affiliations
                [01] orgnameUniversidade Federal de São Paulo orgdiv1Departamento de Medicina
                [02] orgnameUNIFESP orgdiv1Departamento de Cirurgia
                Article
                S0101-28002011000200010 S0101-2800(11)03300200010
                10.1590/S0101-28002011000200010
                878d9116-94ea-4332-9234-0edbcf7cbb0c

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 07 April 2011
                : 31 January 2011
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 23, Pages: 9
                Product

                SciELO Brazil

                Categories
                Artigos Originais

                Logistic models,Graft rejection,Survival analysis,Pancreas transplantation,Transplante de rim,Transplante de pâncreas,Rejeição de enxerto,Análise de sobrevida,Modelos logísticos,Kidney transplantation

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