RESUMEN
Many islet transplant recipients have medical conditions that could interfere with the accuracy of HbA1c measurements (e.g., anemia/dapsone use). Fructosamine is less prone to have clinical interferences and reflects glucose control in a shorter period of time than HbA1c. This study aimed to validate fructosamine use in islet transplant subjects and to evaluate its effectiveness as a predictor for islet graft dysfunction. Thirty-three islet transplant recipients who had concomitant fructosamine and HbA1c data available were retrospectively analyzed. HbA1c, fructosamine, mean capillary blood glucose, and islet graft function (fasting C-peptide/glucose ratio) were assessed. There was a significant and positive association between fructosamine and HbA1c (p < 0.0001). Both variables were also positively associated with mean overall and fasting capillary glucose. Neither fructosamine nor HbA1c was shown by ROC analysis to significantly discriminate between periods with and without subsequent graft dysfunction. HbA1c >6% was predictive of this outcome 1 month in advance (OR 2.95, p = 0.003). However, although significantly associated with graft dysfunction, use of this cutoff as a predictor of dysfunction has poor sensitivity (50%) and specificity (77.6%). Fructosamine above the normal range (>270 mumol/L Quest Diagnostics) was also predictive of ensuing dysfunction (OR 2.47, p = 0.03); however, it had similarly poor sensitivity (62%) and specificity (64%). Fructosamine can be used as an alternative to HbA1c for glycemic assessment in islet transplant recipients in situations with HbA1c assay interference. Neither HbA1c nor fructosamine are good predictors of islet graft dysfunction.
Asunto(s)
Fructosamina/sangre , Trasplante de Islotes Pancreáticos , Adulto , Biomarcadores/sangre , Glucemia/análisis , Femenino , Hemoglobina Glucada/análisis , Humanos , Islotes Pancreáticos/fisiopatología , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
BACKGROUND: To investigate whether changes of nutritional status and behavior are associated with islet transplantation (ITx) and to assess their possible mechanisms. METHODS: In this observational study, 52 subjects with type 1 diabetes, 30 of whom received ITx, underwent nutritional assessments. The study consisted of questionnaires complemented by a dietary intake recording, anthropometric measurements, and body composition analysis. Laboratory tests were also reviewed as part of the follow up. RESULTS: After ITx, significant reductions in body weight (3.7 kg; P<0.0001), body mass index (1.39 kg/m2; P<0.0001), waist circumference (3.96 cm; P=0.006), and fat weight (3.28 kg; P<0.01) were observed. The average consumption of carbohydrate and protein were also lower than pretransplant, together with some micronutrients (vitamins B12 and B6, zinc, and phosphorus). Insulin administration and changes in A1C were not associated with a significant change in anthropometric measurements. Subjects on exenatide after ITx showed significantly lower weight and body mass index than those not taking exenatide. CONCLUSIONS: ITx is associated with modifications in nutritional behavior and status. Drugs and health conditions are likely to be at least in part responsible for these changes, but a voluntary modification of eating habits by the patients also plays a role. Strict monitoring of nutritional parameters, counseling by experts in nutrition, and multivitamin/mineral supplement after ITx could be of benefit to the patients.
Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos/fisiología , Trasplante de Islotes Pancreáticos/psicología , Estado Nutricional , Adulto , Índice de Masa Corporal , Trasplante de Médula Ósea/fisiología , Trasplante de Médula Ósea/psicología , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/rehabilitación , Dieta para Diabéticos , Ingestión de Energía , Exenatida , Estudios de Seguimiento , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Entrevistas como Asunto , Trasplante de Riñón/fisiología , Trasplante de Riñón/psicología , Péptidos/uso terapéutico , Percepción , Encuestas y Cuestionarios , Ponzoñas/uso terapéuticoRESUMEN
BACKGROUND: A current limitation of islet transplantation is reduced long-term graft function. The glucagon-like peptide-1 receptor agonist, exenatide (Byetta, Amylin Pharmaceuticals, CA) has properties that could improve existing islet function, prevent further loss of islet mass and possibly even stimulate islet regeneration. METHODS: This prospective study evaluated the safety, efficacy, and metabolic effects of exenatide in subjects with type 1 diabetes mellitus and islet allograft dysfunction requiring exogenous insulin. RESULTS: Sixteen subjects commenced exenatide, 12 continue (follow-up 214+/-57 days; range 108-287), four (25%) discontinued medication because of side effects. At 6 months, exogenous insulin was significantly reduced with stable glycemic control (0.15+/-0.02 vs. 0.11+/-0.025 U/kg per day; P<0.0001); three subjects discontinued insulin from 4, 5, and 9 U/day, respectively, two sustained insulin independence with A1c reduction below graft dysfunction criteria. Postprandial capillary blood glucose was significantly decreased (129.4+/-3.8 vs. 118.7+/-4.6 mg/dL; P<0.001), C-peptide and C-peptide-to-glucose ratio increased significantly by 5th and 6th months of treatment (ratio, 1.09+/-0.15 vs. 1.52+/-0.18; P<0.05). Weight loss more than 3 kg occurred in 8 of 12 (67%) subjects. Stimulation testing demonstrated improved glucose disposal and C-peptide secretion (glucose area under the curve 52,332+/-3,219 vs. 42,072+/-1,965; P=0.002 mg x min x dL, mixed meal stimulation index 0.50+/-0.06 vs. 0.66+/-0.09; P=0.03 pmol x mL), with marked suppression of glucagon secretion and progressive increase in amylin secretion. Side effects were more frequent and severe compared with published reports in type 2 diabetes, tolerated doses were lower. CONCLUSIONS: Exenatide was tolerated in this patient population after appropriate dose titration and there appeared to be gradual but sustained positive effects on glycemic control and islet graft function.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Péptidos/uso terapéutico , Ponzoñas/uso terapéutico , Adulto , Amiloide/sangre , Glucemia/efectos de los fármacos , Péptido C/sangre , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/cirugía , Exenatida , Estudios de Factibilidad , Glucagón/sangre , Rechazo de Injerto/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Inmunosupresores/uso terapéutico , Insulina/uso terapéutico , Polipéptido Amiloide de los Islotes Pancreáticos , Trasplante de Islotes Pancreáticos , Persona de Mediana Edad , Péptidos/efectos adversos , Estudios Prospectivos , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Ponzoñas/efectos adversosRESUMEN
BACKGROUND: The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) have been recognized. METHODS: Herein, we present the clinical outcome of a single-center pilot trial of islet after kidney (IAK) transplantation in seven patients with T1DM. The immunosuppression protocol for the kidney graft was converted to sirolimus+tacrolimus regimen 6 months before islet transplantation to exclude negative effects on kidney graft function. Primary endpoint was achievement of insulin independence after transplantation. Clinical outcome, metabolic control, severe hypoglycemia, kidney function, Quality of Life (QOL) psychometric measures, and adverse events were monitored. RESULTS: Seven patients showed graft function with improved metabolic control (A1c, fasting glycemia, and metabolic tests) after IAK (14,779+/-3,800 IEQ/kg). One-year insulin independence was 30% with persistent graft function in 86% (C-peptide-positive). A1c reduction was 1.95+/-0.31% from baseline (P<0.0001). No episodes of severe hypoglycemia were observed, even after resuming insulin. The direct consequence of these benefits was a significant improvement in diabetes QOL. Adverse events included procedure-related pleural effusion (n=2), cholecystitis (n=1), and additional immunosuppression-related, all resolved without sequelae. Kidney function (by estimated glomerular filtration rate) remained stable during follow-up in six of seven patients. CONCLUSIONS: Islet transplantation represents a feasible therapeutic option for patients with T1DM bearing a stable kidney allograft. Insulin independence at 1 year is lower than what reported in islet transplant alone. Nevertheless, clear benefits in terms of optimal metabolic control and absence of severe hypoglycemia are invariably present.
Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Nefropatías Diabéticas/cirugía , Trasplante de Islotes Pancreáticos/fisiología , Trasplante de Riñón/fisiología , Calidad de Vida , Adulto , Glucemia/metabolismo , Femenino , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Islotes Pancreáticos/inmunología , Trasplante de Islotes Pancreáticos/psicología , Pruebas de Función Renal , Trasplante de Riñón/inmunología , Trasplante de Riñón/psicología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Allogeneic islet transplantation is becoming a treatment option for patients with unstable type 1 diabetes mellitus (T1DM). Around 80% of the islet recipients achieve insulin independence after one or two islet infusions under "Edmonton-like" immunosuppressive protocol, but only 10% will remain insulin independent over the long term. Islet transplantation leads to glucose stabilization, and severe hypoglycemia is prevented even in patients back on insulin injections. Thus, islet transplantation has achieved the proposed targets in patients with unstable T1DM: normalizing blood glucose and hemoglobin A(1c), preventing severe hypoglycemic episodes, and improving quality of life. The current aims of islet transplantation programs are to maintain the success achieved and to overcome remaining obstacles and limitations.
Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos/métodos , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Hemoglobina Glucada/metabolismo , Humanos , Trasplante de Islotes Pancreáticos/efectos adversos , Calidad de Vida , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Tacrolimus is an immunosuppressive agent used in solid organ and islet transplantation. Its topical form has shown benefit in the treatment of inflammatory skin conditions. Although tacrolimus has a wide spectrum of side effects, dermatological complications related to systemic tacrolimus therapy are limited in the literature. Atopic dermatitis (AD) is a chronic pruritic cutaneous condition that usually begins in infancy and is characterized by an increased Th2 response. We report the case of a patient with type 1 diabetes mellitus (T1DM) and history of AD latent for 10 years who developed severe dermatitis and alopecia 5 months after undergoing allogeneic islet transplantation and initiating a steroid-free immunosuppressive regimen with sirolimus and tacrolimus maintenance. After exclusion of other possible causes for the progression and exacerbation of the clinical presentation of AD, discontinuation of tacrolimus and introduction of mycophenolate mofetil resulted in full remission of the symptoms. The beneficial effects of tacrolimus withdrawal suggest a cause-effect relationship between this adverse event and the utilization of the drug. Islet graft function remained stable after modification of the therapeutic regimen (stable glycemic control and unchanged C-peptide).
Asunto(s)
Dermatitis Atópica/etiología , Diabetes Mellitus Tipo 1/cirugía , Inmunosupresores/efectos adversos , Trasplante de Islotes Pancreáticos , Tacrolimus/efectos adversos , Adulto , Alopecia Areata/patología , Alopecia Areata/prevención & control , Dermatitis Atópica/patología , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Inmunosupresores/uso terapéutico , Tacrolimus/uso terapéutico , Trasplante Homólogo , Resultado del TratamientoAsunto(s)
Bezoares/etiología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Gastroparesia/etiología , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/efectos adversos , Péptidos/efectos adversos , Ponzoñas/efectos adversos , Adulto , Bezoares/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/cirugía , Endoscopía Gastrointestinal , Exenatida , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Trasplante de Islotes Pancreáticos , Trasplante de Riñón , Péptidos/uso terapéutico , Ponzoñas/uso terapéuticoRESUMEN
BACKGROUND: The success of sirolimus and low-dose tacrolimus in islet cell transplantation has influenced many transplant centers to utilize this novel regimen. The long-term safety and tolerability of this steroid-free immunosuppressive protocol for allogeneic islet transplantation has yet to be determined. METHODS: We transplanted 26 adult patients with long standing type 1 diabetes mellitus between April 2000 and June 2004. Immunosuppression consisted of induction with daclizumab and maintenance therapy with tacrolimus and sirolimus. Adverse events (AEs) in patients were followed and graded using the Common Terminology Criteria for Adverse Events, version 3.0 (National Cancer Institute). RESULTS: To date, the majority of patients were able to remain on the immunosuppression combination for up to 22+/-11 months. Four patients were successfully converted to Mycophenolate Mofetil due to tacrolimus-related toxicity. Withdrawal from immunosuppression was decided in four patients due to hypereosinophilic syndrome, parvovirus infection, aspiration pneumonia, and severe depression, respectively. Six patients required filgrastim therapy for neutropenia. Transient elevation of liver enzymes was observed in most patients early after islet infusion. Increased LDL in 20 patients required medical treatment. CONCLUSION: There was a varying range of AEs, most of them mild and self-limiting; however, some required urgent medical attention. The majority of patients were able to tolerate and remain on this effective regimen. To date, no deaths, cytomegalovirus disease, graft-versus-host disease, or posttransplant lymphoproliferative disease has been observed.
Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Terapia de Inmunosupresión/efectos adversos , Trasplante de Islotes Pancreáticos/inmunología , Complicaciones Posoperatorias/inducido químicamente , Adulto , Péptido C/sangre , Femenino , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo/inmunologíaRESUMEN
OBJECTIVE: The association between parity and type 2 diabetes has been studied in developed countries and in Singapore and Chinese women but not in Hispanics. Herein we evaluated the association between parity (number of live births) with diabetes in a group of Hispanic postmenopausal women from Colombia. RESEARCH DESIGN AND METHODS: Herein we evaluated the association between parity and diabetes in a population of 1,795 women from Colombia. Women were divided in birth categories (0 [referent], 1 or 2, 3-5, 6 or > births). Medical history of diabetes and anthropometric characteristics were recorded. Logistic regressions were performed in order to find the association between parity and diabetes in bivariable and multivariable models after controlling for age, body mass index (BMI), waist hip ratio (WHR) and diabetes family history, among other variables. RESULTS: In our study, there was an association between parity and diabetes after adjusting for age, BMI and diabetes family history in the multiparous women groups when compared to the women with no births (Referent group) [1-2 births vs. referent OR 5.2 (95 CI 1.2-22.9), 3-5 births vs. referent OR 5.5 (1.3-23.0) and ≥6 births vs. referent OR 7.5 (1.8-31.8), respectively]. The association was maintained in two of the groups in the multivariable analysis [OR 5.0 (1.1-22.9) and 5.3 (1.2-23.5)], for 1 or 2 births and 6 or > births versus 0 births, respectively. Positive diabetes family history and WHR were also associated with an increased risk of diabetes [OR 4.6 (3.0-7.0) and 4.1 (2.0-8.1), respectively]. CONCLUSIONS: In postmenopausal Hispanic women, multiparity, as well as a positive family history of diabetes and a high waist-hip ratio were associated with higher diabetes risk.
RESUMEN
BACKGROUND: Transplantation of allogeneic tissues is becoming a wider practice for the replacement of organ function lost to congenital or acquired pathologies. Chronic immunosuppression remains a necessity to prevent organ rejection, despite increased risks of infection, organ toxicity, and malignancies. Abnormalities of female gonadal function in patients of reproductive age are recognized, however, pathological alterations of the reproductive system in patients treated with new generation immunosuppressive drugs are still poorly documented. METHODS: We report herein our observations of abnormalities of the reproductive system in 13 female recipients of allogeneic islets for type 1 diabetes, under immunosuppression therapy based on daclizumab induction and tacrolimus/sirolimus maintenance. RESULTS: Menstrual cycle alterations and clinically significant ovarian cysts were frequently observed in our patients, some requiring medical or surgical intervention. All ovarian cysts appeared of benign nature. CONCLUSIONS: Our findings suggest that pre- and posttransplant evaluation of female patients should include menstrual history, baseline pelvic ultrasound, and hormonal levels to assess the presence and monitor the progression of such alterations.
Asunto(s)
Trasplante de Islotes Pancreáticos/efectos adversos , Ciclo Menstrual , Ovario/fisiopatología , Adolescente , Adulto , Preescolar , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Inmunosupresores/efectos adversos , Hormona Luteinizante/sangre , Persona de Mediana Edad , Quistes Ováricos/etiología , Pelvis/diagnóstico por imagen , Progesterona/sangre , UltrasonografíaRESUMEN
Enhancing drug development for pediatric disease is a priority and a public responsibility. The Creating Hope Act of 2010 is important new proposed legislation that adds drugs and biologics for treating rare diseases in children to those for neglected tropical diseases as eligible for a priority review voucher from the U.S. Food and Drug Administration. The Act enhances existing incentive programs through specific financial benefits to companies who seek a pediatric indication for a new drug to treat an orphan disease that occurs specifically in children.
Asunto(s)
Industria Farmacéutica/tendencias , Producción de Medicamentos sin Interés Comercial/legislación & jurisprudencia , Niño , Aprobación de Drogas/economía , Aprobación de Drogas/legislación & jurisprudencia , Diseño de Fármacos , Industria Farmacéutica/economía , Política de Salud , Humanos , Enfermedades Desatendidas , Producción de Medicamentos sin Interés Comercial/economía , Pediatría/métodos , Enfermedades Raras/tratamiento farmacológico , Estados Unidos , United States Food and Drug AdministrationRESUMEN
The aim of this study was to evaluate the importance of nonalbumin-predominant proteinuria on kidney function (KF) after islet transplantation (ITx). Twenty-four-hour proteinuria and albuminuria were available in 27 recipients. KF was assessed by serum creatinine and estimated glomerular filtration rate (eGFR) was calculated by Modification of Diet in Renal Disease formula. Correlations between eGFR and albuminuria (r = -0.422, p < 0.001) were higher than with proteinuria (r = -0.223, p < 0.001; p = 0.006 for comparison between correlations). Nineteen (70%) subjects had proteinuria >or= 300 mg/24 h during the follow-up. Subjects were divided into three groups according to urinary protein excretion patterns: no proteinuria (n = 8), nonalbumin-predominant (n = 8), and albumin-predominant (n = 11) proteinuria. Proteinuria >or= 500 mg/24 h was observed only among patients with albumin-predominant proteinuria (64%; p = 0.002) and these patients had the lowest eGFR means post-ITx (no proteinuria: 84.2 +/- 16.4 vs. nonalbumin: 69.1 +/- 13.8 vs. albumin-predominant proteinuria: 65.5 +/- 16.6 ml/min/1.73 m(2), p = 0.044 for first vs. last group). In conclusion, high frequency of proteinuria was observed after ITx. However, it seems to be milder and have less impact on KF when albumin is not the major source of proteinuria. Prospective evaluation of proteinuria, including tubular function markers, should be performed to elucidate the mechanisms of kidney damage in this population.
Asunto(s)
Diabetes Mellitus/terapia , Inmunosupresores/efectos adversos , Trasplante de Islotes Pancreáticos/efectos adversos , Enfermedades Renales/fisiopatología , Complicaciones Posoperatorias/fisiopatología , Proteinuria/fisiopatología , Adulto , Albúminas/metabolismo , Causalidad , Células Cultivadas , Estudios de Cohortes , Creatinina/sangre , Complicaciones de la Diabetes/fisiopatología , Complicaciones de la Diabetes/orina , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Trasplante de Islotes Pancreáticos/inmunología , Enfermedades Renales/inducido químicamente , Pruebas de Función Renal , Túbulos Renales/efectos de los fármacos , Túbulos Renales/fisiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/prevención & control , Proteinuria/inducido químicamente , Proteinuria/prevención & control , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE To evaluate if baseline serum lipids are associated with islet graft survival in type 1 diabetes islet transplant (ITx) recipients. RESEARCH DESIGN AND METHODS Baseline fasting lipid profile was collected from 44 ITx recipients. Comparisons were performed between subjects below and above the median values of each lipid fraction. Differences in outcomes were compared by Kaplan-Meier curves and Cox regression analysis. RESULTS Subjects with baseline fasting plasma triglycerides and VLDL cholesterol above the median had shorter islet graft survival (triglycerides: 39.7 +/- 6.1 vs. 61.3 +/- 6.6 months, P = 0.029, and VLDL: 41.5 +/- 5.7 vs. 62.8 +/- 7.3 months, P = 0.032). Total, LDL, and HDL cholesterol did not influence islet function. Triglycerides (odds ratio 2.97 [95% CI 1.03-8.52], P = 0.044) maintained its association with graft failure after adjustments for confounders. CONCLUSIONS Higher baseline triglycerides are associated with earlier decline in islet graft function. Prospective clinical trials should address whether it is directly caused by lipotoxicity and if strategies focusing on lowering serum lipids may prolong islet graft survival.
Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Supervivencia de Injerto , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos/patología , Lípidos/efectos adversos , Lípidos/sangre , Adulto , Estudios de Cohortes , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/patología , Estudios de Seguimiento , Supervivencia de Injerto/efectos de los fármacos , Humanos , Trasplante de Islotes Pancreáticos/rehabilitación , Lípidos/farmacología , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
BACKGROUND: Body fat accumulation decreases insulin sensitivity. It has being associated with earlier onset of type 1 diabetes mellitus (DM) and islet graft failure. The aim of this study was to evaluate whether insulin resistance, characterized by risk factors for type 2 DM, can predict islet graft survival in type 1 DM islet transplant (ITx) recipients. METHODS: Demographic, anthropometrical, and laboratory data, as well as family history of type 2 DM (first degree relatives), were collected from 44 ITx recipients. Risk factors for type 2 DM, such as positive family history of type 2 DM (n=11) and overweight (body mass index >25 kg/m2; n=14), were analyzed separately and in combination, which was designated as "type 2 DM phenotype" (n=5). Differences in outcomes (time-to-graft dysfunction and failure) were compared using Kaplan-Meier curves. Cox regression analysis was performed to control for possible confounding factors. RESULTS: Neither positive family history of type 2 DM nor overweight at baseline could predict islet function outcomes after ITx. However, when both risk factors were grouped, the "type 2 DM phenotype" was associated with earlier islet graft failure (mean estimate graft survival 25.7+/-9.1 vs. 54.1+/-5.2 months, P=0.022). These results were sustained after adjustments for confounding variables (OR 5.20, 95% CI 1.12-24.0). CONCLUSIONS: Predisposition for type 2 DM can coexist with the type 1 DM phenotype and is associated with earlier decline in islet graft function. Prospective clinical trials should address whether it is associated with decreased insulin sensitivity and if insulin sensitizers play a role in prolonging islet graft survival.
Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Diabetes Mellitus Tipo 2/metabolismo , Supervivencia de Injerto , Resistencia a la Insulina , Trasplante de Islotes Pancreáticos , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Proteinuria development and decrease in glomerular filtration rate (GFR) have been observed after successful islet transplantation. The aim of this study was to determine clinical, laboratory, and immunosuppressant-related factors associated with kidney dysfunction in islet transplant recipients. METHODS: A retrospective cohort study was conducted in 35 subjects submitted to pancreatic islet transplantation for treatment of unstable type 1 diabetes mellitus. Demographic, anthropometrical, and laboratory data, as well as immunosuppressive and antihypertensive therapy were recorded. Kidney function was assessed by albuminuria and estimated GFR (eGFR), calculated by modification of diet in renal disease formula. RESULTS: Age was the only independent risk factor for low eGFR (<60 mL/min/1.73 m2) (odds ratio [OR]=1.78 [1.22-2.61]). Low-density lipoprotein cholesterol (OR=2.90 [1.37-6.12]) and previous microalbuminuria (OR=6.42 [1.42-29.11]) were risk factors for transient macroalbuminuria. Interestingly, tacrolimus was a protective factor for macroalbuminuria (OR=0.12 [0.06-0.26]). Six of 30 (20%) normoalbuminuric subjects at baseline progressed to microalbuminuria. No subject developed sustained macroalbuminuria. Surprisingly, overall eGFR remained stable during follow-up (before transplant: 74.0+/-2.0; during immunosuppressive therapy: 75.4+/-2.8; and after withdrawal: 76.3+/-5.3 mL/min/1.73 m2; P>0.05). Even subjects with low eGFR and microalbuminuria at baseline (n=10) maintained stable values posttransplantation (61.13+/-3.25 mL/min/1.73 m2 vs. 63.32+/-4.36 mL/min/1.73 m2, P=0.500). CONCLUSIONS: Kidney function remained stable after islet transplantation alone. The unchanged kidney function found in this sample may be attributed to healthier kidney status at baseline and possibly to prompt treatment of modifiable risk factors. Aggressive treatment of risk factors for nephropathy, such as blood pressure, low-density lipoprotein cholesterol, and careful tacrolimus levels monitorization, should be part of islet transplant recipient care.