Simultaneous pancreas-kidney transplantation: evaluation of graft function, cholesterol, triglycerides, and immunosuppressive regimens.

AIMS: To evaluate pancreas graft function, use of insulin, cholesterol, triglyceride levels, prescription of lipid-lowering drugs, and immunosuppressive regimens among recipients of simultaneous pancreas-kidney transplants (SPKT), who had initial immunosuppression with tacrolimus, sirolimus, and corticosteroids. METHODS: From 2000 to 2007, we performed 73 SKPT, among which we conducted a retrospective data analysis on 51 medical records of patients who had been followed for at least 6 to 72 months. We excluded from the analysis eight recipients who died before 6 months: eight with early pancreas graft losses and six for continued follow-up in other centers. RESULTS: There were four pancreas graft losses after 6 months due in two diabetes mellitus recurrence, one posttuberculosis treatment, and one after use of nonsteroidal inflammatory medication. Mean plasma glucose levels ranged from 84 to 103 mg/dL, while glycosylated hemoglobin (HbA1) levels ranged from 5.7% to 6.2%. At 6, 12, 36, and 60 months, 80%, 91%, 86%, and 75% of recipients, respectively, had HbA1 lower than 6.5%. In the same period, 10%, 8%, 10%, and 11% of recipients became insulin-dependent. Mean cholesterol levels (mg/dL) at 6, 12, 36, and 60 month were 190, 180, 196 and 193, while triglyceride levels (mg/dL) were 162, 129, 106, and 113 respectively. Recipient's rate of lipid-lowering drug use was 18%, 21%, 20%, and 22% at 6, 12, 36, and 60 months. Mean serum creatinine levels (mg/dL) with standard deviations were 1.3 +/- 0.4, 1.5 +/- 0.4, 1.6 +/- 0.5, 1.8 +/- 0.9, at 6, 12, 36 and 60 months respectively. Nineteen recipients had sirolimus suspended and 14 recipients, tacrolimus suspended as well for various reasons. CONCLUSION: Mean plasma glucose levels were normal during the period. About 10% of recipients became insulin-dependent and 20% required lipid-lowering drugs. The immunosuppressive regimen protocol had to be changed in 60% of patients.

Parasitic infection in renal transplant recipients.

The purpose of this study was to evaluate the prevalence of symptomatic parasitic infections in adult renal transplant recipients. We retrospectively analyzed a sample of 657 adult renal transplant recipients performed from January 2001 to December 2005 for immunosuppression protocol, clinical manifestations, parasite diagnosis, treatments, and outcomes. The prevalence of symptomatic parasitosis infections was 2.4% (16/657). None of the infected patients received cyclosporine in their immunosuppression protocol. Most of the infections were caused by Strongyloids stercoralis (n = 11), followed by Giardia lamblia (n = 3), Toxoplasma gondii (n = 1), and Trypanosoma cruzi: (n = 1). Strongyloides stercoralis was the most frequent agent, causing three cases of hyperinfection including one fatal case. With the new immunosuppressive regimes there must be a suspicion of parasitic infection to avoid the diagnostic delay that can be fatal. Strategies, including empiric treatment for S. stercoralis, must be considered.

Expanding criteria for the use of living donors: what are the limits?

The cadaver organ shortage has pushed the transplant community to extend the boundaries beyond the traditional criteria used for living donor transplantation. This new liberal policy involves: (1) the type of donor, such as emotionally related individuals, the direct or indirect interchange of donors, anonymous as well as rewarded donation; (2) challenging immunological criteria, using incompatible ABO blood types and or transplantation across a positive cross-match; (3) relaxing clinical criteria related to elderly, hypertensive, or obese donors, or patients with nephrolithiasis, fibromuscular renal artery disease, hematuria, or renal cell carcinomas. However, these practices may be dangerous. They must be clearly validated to promote a liberal policy of donor acceptance since it may carry a risk for both the donor and the recipient as well as for society. It is crucial to ensure the physical integrity of the donor as well as to provide guarantees, for instance a 1-year policy of life insurance, an indefinite long-term medical follow-up and the assurance of going to the top of the waiting list if the donor becomes uremic in the future.

Pregnancy outcome after renal transplantation.

AIMS: The aim of our study was to evaluate the frequency and the outcome of pregnancies in renal transplant recipients at our center. METHODS: This study involved the retrospective analysis of 405 childbearing female renal recipients for presence of risk factors, the outcome of pregnancy, and maternal and fetal complications. RESULTS: Fourty-four pregnancies occurred in 41 patients (10.8%). Mean age at transplantation was 23.6 +/- 6.3 years (range, 12-38 years). Only in 5 pregnancies were there no risk factors. In 13 (29.5%) pregnancies, the previous creatinine level was >1.5 mg/dL, in 16 (36.45%), proteinuria was >500 mg/24 hours; 29 (65.9%) were hypertensive; 14 (31.8%) had a time between transplantation and pregnancy less than 2 years (mean time, 35.5 +/- 30.9 months; range, 3-120 months). The outcomes were 27 (61.4%; 11 term and 16 premature delivery) successful pregnancies, 6 (13.6%) spontaneous abortions, 10 (22.7%) therapeutic abortions, and 1 (3.2%) fetal death. Pre-eclampsia occurred in 9 (20.4%) pregnancies and eclampsia in 1 (2.2%). The mean weight of the offspring was 2195 +/- 490 g (range, 1300- 2980 g). There were 2 cases of acute fetal distress and 1 oligodramnios. Median creatinine level was 1.0 (range, 0.4-3.0) mg/dL before conception and 1.2 (range, 0.7-9.0) mg/dL 6 month after pregnancy (P <.001). The long-term patient and graft survival rates were similar for pregnant versus nonpregnant recipients in the childbearing age. CONCLUSION: Most pregnancies were successful, although the premature delivery rate was high (36.4%). Only 5 conceptions occurred in the absence of risk factors. Pregnancy did not impair the patient and graft survival during long-term follow-up.

Immunosuppression in pancreas transplantation: mycophenolate mofetil versus sirolimus.

The use of mycophenolate mofetil (MMF) in pancreas transplantation has increased graft survival and decreased the incidence of acute rejections episodes (ARE), regardless of the choice of calcineurin inhibitor. The combination of MMF with tacrolimus (TAC) is the most common protocol, it is considered the gold standard for new protocols. In the last few years, there have been reports of a small number of patients treated with sirolimus (RAPA), usually combined with TAC. Patient and pancreas survival rates as well as the incidence of ARE were similar to protocols with TAC and MMF. Twenty simultaneous pancreas and kidney (SPK) transplantations were performed using an immunosuppressive protocol of TAC, RAPA, and steroids (STE) after 2000. The incidence of ARE was 25%; all episodes responded to STE. Only 2 patients (10%) displayed hypercholesterolemia requiring treatment with statins. The use of RAPA as an alternative to MMF is promising, although presently one with limited experience. The combination of MMF and RAPA with or without a calcineurin inhibitor is an option to be evaluated in the future.

Building bone tissue: matrices and scaffolds in physiology and biotechnology

Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies

Building bone tissue: matrices and scaffolds in physiology and biotechnology.

Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies.

Update of 156 episodes of central nervous system bleeding in hemophiliacs.

Between 1960 and 1991, 156 episodes of central nervous system (CNS) bleeding were documented in 106 patients from a total population of 1,410 hemophiliacs (7.5%). Ninety-one hemophilia A patients presented 131 bleeding episodes; 15 hemophilia B patients had 25 episodes. 32% of these episodes took place in patients less than 5 years of age. 46% were age 10 or less, and 72% were age 20 or less. The mean age was 14.8 years in hemophilia A and 9 years in hemophilia B patients. A significant increase in the mean age of hemophilia A patients has been observed over the last 10 years; this may be related to HIV infection. A history of recent trauma was documented in 39.7% of the episodes. Spontaneous CNS bleeding was predominant in severe hemophilia (85.2%). One hundred and fifty-four CNS bleeding episodes were intracranial and 2 intraspinal. Of the intracranial episodes, 37.7% were subarachnoid, 29.8 subdural, and 22.7% intracerebral. Factor VIII or IX inhibitors were present in 11.3% of the patients; this figure is slightly lower than that observed in our total hemophilic population. Over 50% of the patients had psychoneurological sequelae; the most frequent were seizure disorders and motor impairment. The overall mortality rate was 29.2%. The mortality was more closely related to the CNS bleeding site than to the severity of hemophilia. Treatment should be based on prompt and prolonged replacement therapy to ensure hemostatic levels of antihemophilia factors.

Resultados de los estudios seroepidemiologicos y cultivo de virus HIV en pacientes hemofílicos / Results of seroepidemiologic studies and culture of HIV virus in hemophilic patients

Del estudio realizado en nuestra población de pacientes hemofílicos, concluimoss que la incidência de seroprevalencia Anti-HIV es de 34,3%, y que el porcentaje de SIDA en la población estudiada es del 7,25% (33/455). Teniendo presente que el número de enfermos declarados en la República Argentina al 30/7/88 es de 197 casos, el porcentaje de pacienes hemofílicos en este grupo es del 16,7%, lo que constituye una cifra muy superior a las de otras estadísticas mundiales. Interpretamos que este resultado es debido, en primer término, a que la población de enfermos hemofílicos ha sido más homogéneamente estudiada que el resto de personas que integran las otras poblaciones de riesgo para contraer la enfermedad, y en segundo lugar, a que la prevalencia del virus en estas poblaciones (drogadictos y homosexuales) no ha tenido o no demuestra en la actualidad la mismo difusión o velocidad de difusión que en otras comunidades del resto del mundo. La trasmisión comprobada en parejas sexuales estables de pacientes hemofílicos es del 22%, cifra que no difiere de la incidencia de transmisión referida por otros estudios

Detección de portadores de hemofilia A: complementación de los estudios convencionales con el análisis de ADN / Detection of haemophilia A patients: complementation of the conventional study with DNA analysis

Con el propósito de evaluar la utilidad de complementar los estudos convencionales mediante el análisis del ADN con sondas extragénicas, para la detección de portadoras, estudiamos 60 individuos pertenecientes a 15 familias argentinas con uno (9) o más (6) miembros afectados de hemofilia. A severa. Realizamos el análisis de segregación de los enfermos polimórficos (RFLP), luego del tratamiento del ADN con TaqI/ST14, en 21 varones (15 hemofílicos) y 39 mujeres - 6 portadoras obligadas (PO) y 33 potenciales (PP) -, además de la determinación de la actividad del factor VIII (FVIII) y del antígeno del factor von Willebrand (vWFAg). La probabilidad de ser portadora de cada consultante, fue asignada según los métodos convencionales (antecedentes familiares y niveles de FVIII y vWFAg) y combinada con los resultados del análisis de los RFLP, expresados en términos de probabilidad. ST14 fue informativa en el 67% de las PO y en el 79% de las PP. El análisis de los RFLP permitió definir el estado portador (4,5% de riesgo de recombinación) en el 53% de las familias. En los casos con antecedentes previos, pudimos clasificar 5 de las 10 PP (1 portadora, 4 no-portadoras). El estado portador pudo ser excluido en 5 de 23 mujeres, parientes de hemofílicos esporádicos. En ciertos casos (5/10) observamos una falta de coincidencia entre el genotipo asignado y el fenotipo, probablemente por efecto del fenómeno de Lyon (inactivación al azar de uno de los cromosomas X), aunque no puede excluirse una recombinación entre el locus ST14 y el gen del FVIII. Los resultados del análisis de los RFLP fueron expresados en términos de probabilidad y combinados con los datos fenotípicos; las probabilidades así estimadas fueron bajas (< 0,13) o altas (> 0,95), contrariamente o lo obtenido al considerar exclusivamente los métodos convencionales (0,01 a 0,99). el análisis de segregación de los RFLP disminuye pues, considerablemente la incertidumbre sobre la probabilidad de ser portadora de cada consultante

Resultados de los estudios seroepidemiologicos y cultivo de virus HIV en pacientes hemofílicos / Results of seroepidemiologic studies and culture of HIV virus in hemophilic patients

Del estudio realizado en nuestra población de pacientes hemofílicos, concluimoss que la incidÛncia de seroprevalencia Anti-HIV es de 34,3%, y que el porcentaje de SIDA en la población estudiada es del 7,25% (33/455). Teniendo presente que el número de enfermos declarados en la República Argentina al 30/7/88 es de 197 casos, el porcentaje de pacienes hemofílicos en este grupo es del 16,7%, lo que constituye una cifra muy superior a las de otras estadísticas mundiales. Interpretamos que este resultado es debido, en primer término, a que la población de enfermos hemofílicos ha sido más homogéneamente estudiada que el resto de personas que integran las otras poblaciones de riesgo para contraer la enfermedad, y en segundo lugar, a que la prevalencia del virus en estas poblaciones (drogadictos y homosexuales) no ha tenido o no demuestra en la actualidad la mismo difusión o velocidad de difusión que en otras comunidades del resto del mundo. La trasmisión comprobada en parejas sexuales estables de pacientes hemofílicos es del 22%, cifra que no difiere de la incidencia de transmisión referida por otros estudios (AU)

Detección de portadores de hemofilia A: complementación de los estudios convencionales con el análisis de ADN / Detection of haemophilia A patients: complementation of the conventional study with DNA analysis

Con el propósito de evaluar la utilidad de complementar los estudos convencionales mediante el análisis del ADN con sondas extragénicas, para la detección de portadoras, estudiamos 60 individuos pertenecientes a 15 familias argentinas con uno (9) o más (6) miembros afectados de hemofilia. A severa. Realizamos el análisis de segregación de los enfermos polimórficos (RFLP), luego del tratamiento del ADN con TaqI/ST14, en 21 varones (15 hemofílicos) y 39 mujeres - 6 portadoras obligadas (PO) y 33 potenciales (PP) -, además de la determinación de la actividad del factor VIII (FVIII) y del antígeno del factor von Willebrand (vWFAg). La probabilidad de ser portadora de cada consultante, fue asignada según los métodos convencionales (antecedentes familiares y niveles de FVIII y vWFAg) y combinada con los resultados del análisis de los RFLP, expresados en términos de probabilidad. ST14 fue informativa en el 67% de las PO y en el 79% de las PP. El análisis de los RFLP permitió definir el estado portador (4,5% de riesgo de recombinación) en el 53% de las familias. En los casos con antecedentes previos, pudimos clasificar 5 de las 10 PP (1 portadora, 4 no-portadoras). El estado portador pudo ser excluido en 5 de 23 mujeres, parientes de hemofílicos esporádicos. En ciertos casos (5/10) observamos una falta de coincidencia entre el genotipo asignado y el fenotipo, probablemente por efecto del fenómeno de Lyon (inactivación al azar de uno de los cromosomas X), aunque no puede excluirse una recombinación entre el locus ST14 y el gen del FVIII. Los resultados del análisis de los RFLP fueron expresados en términos de probabilidad y combinados con los datos fenotípicos; las probabilidades así estimadas fueron bajas (< 0,13) o altas (> 0,95), contrariamente o lo obtenido al considerar exclusivamente los métodos convencionales (0,01 a 0,99). el análisis de segregación de los RFLP disminuye pues, considerablemente la incertidumbre sobre la probabilidad de ser portadora de cada consultante (AU)