Predictability of adverse outcomes in hypertensive disorders of pregnancy: a multicenter prospective cohort study.

OBJECTIVES: To explore variables associated with adverse maternal/fetal/neonatal outcomes among pregnant/postpartum patients admitted to ICU for hypertensive disorders of pregnancy (HDP). METHODS: Multicenter, prospective, national cohort study. RESULTS: Variables independently associated with maternal/fetal/neonatal mortality among 172 patients were as follows: Acute Physiology and Chronic Health Evaluation-II (APACHE-II)(OR1.20[1.06-1.35]), gestational age (OR0.698[0.59-0.82]) and aspartate aminotransferase (AST)(OR1.004[1.001-1.006]). Positive likelihood ratio for headache, epigastric pain, and visual disturbances to predict composite adverse outcomes were 1.23(1.16-1.30), 0.76(0.59-1.02), and 1.1(0.98-1.2), respectively. CONCLUSIONS: Maternal/fetal mortality due to HDP was independently associated with severity of illness on admission, gestational age, and elevated AST. Accuracy of clinical symptoms to predict composite adverse outcomes was low.

Calcifilaxis luego del trasplante renal. Reporte de 3 casos clínicos / Calciphylaxis after renal transplant. Three clinical cases report

INTRODUCCIÓN: La calcifilaxis (CFX) es un síndrome caracterizado por depósito de calcio en la capa íntima y media de los vasos, proliferación, fibrosis y trombosis luminal, isquemia y necrosis tisular. Su reporte inicial y descripciones posteriores estuvieron asociados a la insuficiencia renal crónica terminal (IRCT). Hay poca información sobre el efecto que la recuperación de la función renal secundaria al trasplante renal produce en la incidencia de esta patología. MATERIAL Y MÉTODOS: Estudio retrospectivo unicéntrico. Se realizó un análisis retrospectivo de la cohorte de los 448 pacientes trasplantados de riñón y riñón y páncreas entre el 1 de enero de 2001 y el 1 de enero de 2014 en nuestro Servicio. RESULTADOS: Tres pacientes presentaron CFX confirmada por biopsia. En los 3 pacientes la CFX se asoció a hipercalcemia (calcemia promedio 11.5 mg/dl), en 2 de ellos al momento del diagnóstico. La Paratohormona intacta (PTHi) al momento del diagnóstico fue 2pg/ml, 62,3pg/ml y 3561pg/ml respectivamente. Dos pacientes eran diabéticos. Se halló hipoalbuminemia en los 3 pacientes. Sólo un paciente presentó obesidad, hiperfosfatemia y anticoagulación como factores de riesgo agregados. En todos los casos la biopsia proporcionó el diagnóstico de certeza para CFX. La mediana de la creatininemia en el momento del diagnóstico de CFX fue de 1,5 mg/dl (1,2mg/dl; 1,2mg/dl y 2mg/dl respectivamente) y el promedio de tiempo entre el trasplante y el desarrollo de CFX fue de 32 meses. En todos los casos se realizó un estricto control del fósforo, la hipercalcemia, las lesiones dérmicas y se administró tiosulfato de sodio IV durante 7 meses promedio. Se observó hipercalcemia al año post trasplante en el 19,59 % de los 448 pacientes estudiados, la evolución fue favorable dos pacientes, con control de la calcemia y mejoría de las manifestaciones cutáneas, y conservación de la función renal. CONCLUSIONES: La prevalencia de CFX luego de un TxR sobre un total de 448 pacientes trasplantados de riñón y de riñón y páncreas para el periodo 2001/2014 fue del 0,66%, inferior a los reportes de incidencia de CFX en diálisis. Los factores asociados a CFX en nuestros pacientes fueron la hipercalcemia al año post trasplante y al momento del evento, la hipoalbuminemia, la diabetes y los desórdenes de la glándula paratiroidea. La persistencia de la hipercalcemia al año post-trasplante renal debe ser un elemento de alta sospecha clínica de esta complicación

INTRODUCTION: Calciphylaxis (CFX) is a syndrome characterized by deposition of calcium in the intima and media of vessels, intimal proliferation, fibrosis, luminal thrombosis, tissue ischemia and necrosis. Its initial report and subsequent descriptions were associated with chronic renal failure. There is little information regarding the possible effect of the recovery of renal function secondary to kidney transplantation in the incidence of this disease. METHODS: Center retrospective study. We analyze in this report the three cases of patients who developed CFX after a renal transplant within a cohort of 448 kidney and kidney-pancreas transplant patients from January 1th 2001 to January 1th 2014 in our Hospital. RESULTS: Three patients were found to have CFX. All of them had hypercalcemia (serum calcium average 11.5 mg/dl) at first year post transplant and 2 patients at diagnosis of CFX. PTHi in the three CFX patients was 2 pg/ml, 62,3pg/ml and 3561pg/ml respectively. Hypoalbuminemia was found in all patients. Two patients were diabetic. Only one patient was obese and under anticoagulation treatment. In all cases a biopsy provided the diagnosis of certainty for calciphylaxis. Median serum creatinine at diagnosis was 1.5 mg/dl (1.2 mg/dl 1.2 mg/dl and 2 mg/dl, respectively) and the average time between transplantation and calciphylaxis diagnosis was 32 months. In all cases, strict control of phosphorus and hypercalcemia and sodium IV thiosulfate treatment was performed. The evolution was successful in two patients, controlling blood calcium and improving cutaneous manifestations with preservation of renal function. CONCLUSIONS: CFX prevalence in a cohort of 448 kidney and kidney-pancreas transplant patients from 2001 to 2014 was 0.66%, less than reported in dialysis patients. Factors associated with CFX in our patients were hypercalcemia in the first year after renal transplant and at the time of the event, hypoalbuminemia, diabetes and disorders of the parathyroid gland. The persistence of hypercalcemia in the first year after renal transplant should be an element of high clinical suspicion of this complication in the kidney transplant recipients

Kidney transplant recipients infected with blaKPC-2-producingKlebsiella pneumonia / Pacientes trasplantados renales con infección por Klebsiella pneumoniae productora de blaKPC-2

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Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: a proof-of-concept study.

Belatacept provides effective immunosuppression while avoiding the nephrotoxicities associated with calcineurin inhibitors (CNIs). However, existing belatacept-based regimens still have high rates of acute rejection. We hypothesized that therapy with belatacept, mycophenolic acid (MMA), steroids and induction therapy with rabbit anti-thymocyte globulin Fresenius (ATGF), rejection rate could be reduced. Prospective, single center, proof-of-concept study including males and females aged ≥18years, Epstein-Barr virus (EBV)-seropositive recipients of a first, HLA non-identical, live or deceased donor kidney allograft. Only patients with a calculated panel reactive antibody score of 0% were included. Three donors were positive for Chagas disease. Six of twelve patients had at least one infection and five were readmitted to the hospital for treatment. One patient had a Trypanosoma cruzi infection via the graft treated successfully. Median cold ischemia time for the transplant patients with a deceased donor was 21.5h. Mean serum creatinine levels at 1, 3 and 6months were 1.76±0.59, 1.55±0.60 and 1.49±0.60mg/dl, respectively. Two of twelve patients experienced clinical, biopsy-proven rejection, successfully treated with methylprednisolone. No patient developed post-transplant lymphoproliferative disorder (PTLD) or any other malignancy and no patient lost their graft or died during follow-up. The potential of this approach makes it worthy of further investigation.

[Kidney transplantation in patients with donor specific antibodies]. / Trasplante renal en pacientes con anticuerpos dirigidos contra donante.

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex® but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex® should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.

Trasplante renal en pacientes con anticuerpos dirigidos contra donante

En trasplante renal, los anticuerpos donante-específicos por ensayos de fase sólida predicen el rechazo temprano mediado por anticuerpos, incluso con resultados negativos de citometría de flujo o citotoxicidad dependiente del complemento. Aquí se describen los protocolos de inmunosupresión y los resultados a diez meses de cuatro pacientes en los que se detectó anticuerpos donante-específicos anti-antígenos leucocitarios humanos (HLA) por Luminex®, pero no detectados por el método de citotoxicidad dependiente de complemento (CDC) ni por citometría de flujo. Los cuatro pacientes recibieron tratamiento de inducción con 5 dosis de timoglobulina de 1.25 mg/kg y 5 dosis de inmunoglobulina intravenosa (IVIG) de 400 mg/kg. Además, uno recibió 20 mg de basiliximab el mismo día del trasplante y el día 4 postrasplante; otro recibió 3 sesiones de plasmaféresis en los días -5, -3, y -1 y eculizumab en dosis de 1200 mg antes del trasplante, 900 mg el día 1, and 600 mg por semana durante un mes. En todos los casos, la inmunosupresión de mantenimiento consistió en tacrolimus, micofenolato y deltisona. Todos presentaron buenos resultados en el corto plazo. Nuestra experiencia sugiere que los pacientes con anticuerpos donante-específicos anti-HLA detectados solo por Luminex® deben recibir un seguimiento estricto y que en esta población se pueden obtener buenos resultados a partir del uso de terapia de inducción con timoglobulina e IVIG.

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex® but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex® should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.

Trasplante renal en pacientes con anticuerpos dirigidos contra donante

En trasplante renal, los anticuerpos donante-específicos por ensayos de fase sólida predicen el rechazo temprano mediado por anticuerpos, incluso con resultados negativos de citometría de flujo o citotoxicidad dependiente del complemento. Aquí se describen los protocolos de inmunosupresión y los resultados a diez meses de cuatro pacientes en los que se detectó anticuerpos donante-específicos anti-antígenos leucocitarios humanos (HLA) por Luminex«, pero no detectados por el método de citotoxicidad dependiente de complemento (CDC) ni por citometría de flujo. Los cuatro pacientes recibieron tratamiento de inducción con 5 dosis de timoglobulina de 1.25 mg/kg y 5 dosis de inmunoglobulina intravenosa (IVIG) de 400 mg/kg. Además, uno recibió 20 mg de basiliximab el mismo día del trasplante y el día 4 postrasplante; otro recibió 3 sesiones de plasmaféresis en los días -5, -3, y -1 y eculizumab en dosis de 1200 mg antes del trasplante, 900 mg el día 1, and 600 mg por semana durante un mes. En todos los casos, la inmunosupresión de mantenimiento consistió en tacrolimus, micofenolato y deltisona. Todos presentaron buenos resultados en el corto plazo. Nuestra experiencia sugiere que los pacientes con anticuerpos donante-específicos anti-HLA detectados solo por Luminex« deben recibir un seguimiento estricto y que en esta población se pueden obtener buenos resultados a partir del uso de terapia de inducción con timoglobulina e IVIG.(AU)

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex« but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex« should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.(AU)

Trasplante renal en pacientes con anticuerpos dirigidos contra donante. / [Kidney transplantation in patients with donor specific antibodies].

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex« but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex« should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.

Use of belatacept as alternative immunosuppression in three renal transplant patients with de novo drug-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA), a severe complication of renal transplantation, is a pathological process involving microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. It generally appears within the first weeks after transplantation, when immunosuppressive drugs are used at high doses. De novo TMA may also be drug-induced when calcineurin inhibitors or proliferation signal inhibitors are used. We report three cases of de novo drug-induced TMA in renal transplant patients who were managed by replacing calcineurin inhibitors or proliferation signal inhibitors with belatacept, a primary maintenance immunosuppressive drug, which blocks the CD28 costimulation pathway, preventing the activation of T lymphocytes. To identify the cause of TMA, we ruled out HUS, hepatitis C serology, HIV serology, parvovirus B19, cytomegalovirus, anti-HLA antibodies, and prolonged activated partial thromboplastin time. We suspect that the TMA was caused by the calcineurin inhibitors or proliferation signal inhibitors. Belatacept treatment was initiated at a dose of 10 mg/kg on days 1, 5, 14, 28, 60, and 90; maintenance treatment was 5 mg/kg once a month for 1 year. Belatacept, in combination with other agents, prevented graft rejection in three patients.

Use of bortezomib to treat anti-HLA antibodies in renal transplant patients: a single-center experience.

Donor-specific human leukocyte antigen (HLA) antibodies (DSA) are associated with decreased graft survival and may cause graft rejection. Bortezomib, a selective inhibitor of the 26S proteasome developed to treat multiple myeloma, has been used for its anti-plasma cell activity in patients undergoing transplantation. We describe our experience with bortezomib used to reduce anti-HLA antibodies in eight renal transplant patients. Patients received bortezomib (1.3mg/m(2)) on days 1, 4, 8, and 11 beginning when antibodies were detected. It was used alone in one patient and was complemented with plasmapheresis in five patients, with IVIG in one patient, and with IVIG and plasmapheresis in another patient. De novo DSA class II were detected in all eight patients and two also had DSA class I. Antibodies were entirely eliminated in five (62.5%) patients 90 days after treatment but only reduced in the other three (62.5%). Notably, they later increased in one patient. Five (62.5%) patients had AMR, two (25%) had mixed rejection, and one had no rejection. our results suggest that bortezomib is effective for reducing DSA avoiding chronic graft injury.

Clinical experience with thymoglobulin and antithymocyte globulin-Fresenius as induction therapy in renal transplant patients: a retrospective study.

OBJECTIVES: We describe our experiences with, and compare the outcomes of, 2 groups of renal transplant patients treated with thymoglobulin or antithymocyte globulin-Fresenius as induction therapy at transplant to reduce the incidence of acute rejection and prevent delayed allograft function. MATERIALS AND METHODS: Twenty-four recipients of deceased-donor or living-donor kidney transplants received thymoglobulin, and 23 patients received antithymocyte globulin-Fresenius. Patient and graft survival and efficacy and safety were assessed at 3 months. RESULTS: The demographic characteristics of both groups were comparable, but the predominant donor type was significantly different. Incidence of complications, delayed graft function, and creatinine concentrations were comparable in both groups. At 3 months after the transplant, patient survival rate was 92% in the thymoglobulin group and 96% in the antithymocyte globulin-Fresenius group (P > .05), and death-censored graft survival rate for both groups was not significantly different. Average hematocrit and lymphocyte, neutrophil, and platelet counts were comparable in both groups at 3 months' follow-up. Average white blood count at 1 month was significantly different between the groups: at 5.62 ± 2.45 × 103 cells/mm³ in the thymoglobulin group and 7.85 ± 4.10 × 103 cells/mm³ in the ATG-F group (P < .05). CONCLUSIONS: Considering the study design limitations, we observed that our group of treated patients, safety, and efficacy of thymoglobulin and antithymocyte globulin-Fresenius were generally comparable.

Utilización de Eculizumab en un receptor de trasplante renal con altos títulos de anticuerpos preformados anti-HLA donante específico / Use of Eculizumab in a kidney transplant receptor with high levels of donor-specific anti-HLA preformed antibodies

Presentamos un caso en el que, por primera vez en América latina, se utilizó eculizumab, un anticuerpo que inhibe la activación terminal del complemento, para la prevención de rechazo mediado por anticuerpos (RMA) en un receptor de trasplante renal con títulos altos de anticuerpos anti-HLA específico de donante preformados. El paciente, un hombre de 51 años de edad, trasplantado por segunda vez, receptor de un injerto de donante vivo relacionado, recibió, antes del trasplante, cuatro sesiones de plasmaféresis y terapia con tacrolimus y micofenolato sódico hasta el día del trasplante. La terapia de inducción fue con inmunoglobulina antitimocítica e inmunoglobulina intravenosa(IVIg). La administración de eculizumab fue del siguiente modo: 1200 mg. dos horas antes del trasplante; 600mg dentro de las primeras 24 horas posteriores al trasplante; durante un mes, una vez por semana, 600 mg. Al día 30, una dosis de 1200 mg. A un mes del trasplante, el paciente muestra buena función del injerto.

Utilización de Eculizumab en un receptor de trasplante renal con altos títulos de anticuerpos preformados anti-HLA donante específico / Use of Eculizumab in a kidney transplant receptor with high levels of donor-specific anti-HLA preformed antibodies

Presentamos un caso en el que, por primera vez en América latina, se utilizó eculizumab, un anticuerpo que inhibe la activación terminal del complemento, para la prevención de rechazo mediado por anticuerpos (RMA) en un receptor de trasplante renal con títulos altos de anticuerpos anti-HLA específico de donante preformados. El paciente, un hombre de 51 años de edad, trasplantado por segunda vez, receptor de un injerto de donante vivo relacionado, recibió, antes del trasplante, cuatro sesiones de plasmaféresis y terapia con tacrolimus y micofenolato sódico hasta el día del trasplante. La terapia de inducción fue con inmunoglobulina antitimocítica e inmunoglobulina intravenosa(IVIg). La administración de eculizumab fue del siguiente modo: 1200 mg. dos horas antes del trasplante; 600mg dentro de las primeras 24 horas posteriores al trasplante; durante un mes, una vez por semana, 600 mg. Al día 30, una dosis de 1200 mg. A un mes del trasplante, el paciente muestra buena función del injerto.(AU)