RESUMEN
In cyclosporine-based protocols, everolimus is more effective than azathioprine to reduce acute rejection. Ketoconazole may reduce cyclosporine and everolimus requirements. We compared kidney transplant patients treated with everolimus or azathioprine in a ketoconazole- and cyclosporine-based immunosuppressive regimen. This open-label, prospective trial of low immunologic risk patients. Included one group (n = 11) who received everolimus (target blood level, 3-8 ng/mL) and the other (n = 11) azathioprine (2.0-2.5 mg/kg/d). Both received steroids, ketoconazole, and cyclosporine with C(0) targets (ng/mL) in the everolimus group of 200-250, 100-125, and 50-65 for months 1 and 2 and thereafter and in the azathioprine group of 250-300 in month 1, 200-250 in month 2, 180-200 until month 6, and 100-125 thereafter. Their baseline characteristics were similar. Two biopsy-proven acute rejections occurred in each group. Three-year graft and patient survival in both groups was 100%. Creatinine clearances at months 6, 12, 24, and 36 were 63.7 +/- 25.4, 58.9 +/- 24.9, 56.0 +/- 22.9, and 57.0 +/- 27.6 in the everolimus group versus 72.6 +/- 20, 68.6 +/- 21.3, 71.4 +/- 23.2, and 68.4 +/- 19.2 in the azathioprine group (NS for every comparison). Major complications were rare and similar in both groups. Five patients in the everolimus group received simvastatin versus 4 in the azathioprine cohort (P = .53). The average cyclosporine doses to achieve targets were 0.8-1.2 mg/kg in the everolimus group and 1.6-2.2 mg/kg in the azathioprine group. The average everolimus dose after month 2 was 0.75-0.9 mg/d. We concluded that with cyclosporine, ketoconazole, and steroids, everolimus was as effective and safe as azathioprine. Cyclosporine reduction with everolimus did not influence graft survival or function at 3 years.
Asunto(s)
Azatioprina/uso terapéutico , Ciclosporina/uso terapéutico , Cetoconazol/uso terapéutico , Trasplante de Riñón/inmunología , Sirolimus/análogos & derivados , Corticoesteroides/uso terapéutico , Adulto , Colesterol/sangre , Creatinina/metabolismo , Quimioterapia Combinada , Everolimus , Femenino , Antígenos HLA-A/sangre , Antígenos HLA-B/sangre , Humanos , Inmunosupresores/uso terapéutico , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Sirolimus/uso terapéutico , Triglicéridos/sangreRESUMEN
Renal grafts suffer a progressive decrease in glomerular filtration rate (GFR) because of several factors including calcineurin inhibitor (CNI) nephrotoxicity. Switching CNIs to sirolimus may improve this adverse prognosis. We performed a prospective, open-label clinical trial among 18 kidney transplant patients with more than 12 months of evolution (range, 385-1826 days), showing progressive GFR decreases and biopsies with interstitial fibrosis and tubular atrophy (IFTA). Immunosuppressive treatment included cyclosporine, ketoconazole, and steroids associated with azathioprine or mycophenolate mofetil. After signing an Institutional Review Board-approved written consent, cyclosporine was switched to sirolimus seeking to achieve a trough blood sirolimus concentration of 6-15 ng/mL. Wilcoxon and Student's t-tests were used to compare the values in the annual periods before and after the switch. GFR was estimated by the Modification of Diet in Renal Disease formula. There were no acute rejection episodes. Estimated GFR on the day of the switch was 38.0 +/- 12.1 mL/min. After CNI switch, the slope of the estimated GFR significantly improved from -6.5 +/- 9.2 to 8.1 +/- 14.0 mL/min/year (P < .01). The estimated GFR 1 year after the switch was 47.2 +/- 16.9 mL/min (P = .003 vs baseline). Total expenditures increased. The ratio of post-switch versus baseline total expenditures was 1.93 (95% confidence interval, 1.54-2.31) and the ratio of sirolimus to CNI cost was 2.16 (95% confidence interval, 1.53-2.78). Switching from CNI to sirolimus for kidney transplants with decreasing GFR and a biopsy with IFTA changes, suggesting progressive graft nephropathy, almost doubled total expenses. It is necessary to conduct trials using clinical end points to definitively validate this therapeutic intervention.
Asunto(s)
Inmunosupresores/uso terapéutico , Cetoconazol/economía , Cetoconazol/uso terapéutico , Trasplante de Riñón/inmunología , Sirolimus/economía , Sirolimus/uso terapéutico , Antihipertensivos/uso terapéutico , Azatioprina/economía , Azatioprina/uso terapéutico , Presión Sanguínea , Chile , Colesterol/sangre , Análisis Costo-Beneficio , Costos y Análisis de Costo , Ciclosporina/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Inmunosupresores/economía , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/economía , Ácido Micofenólico/uso terapéutico , Proteinuria/epidemiología , Insuficiencia Renal/patología , Triglicéridos/sangreRESUMEN
INTRODUCTION: This study reviewed the course of pregnancies in terms of impact on renal function and delivery-related data among women who received kidney transplants in our unit. METHODS: We reviewed the medical records of women transplanted between 1982 and 2002 who became pregnant. We recorded the data of medical, obstetrical, and transplant-related complications, plasma creatinine levels, and blood pressures at baseline, delivery, and 12 months after delivery. RESULTS: Thirty women had 37 pregnancies. Immunosuppressive protocols included cyclosporine, ketoconazole, azathioprine, and prednisone in 22 patients or azathioprine and prednisone in 15. Renal function decreased significantly: mean creatinine levels at baseline, delivery, and after 1 year were: 1.19 +/- 0.38 mg/dL; 1.44 +/- 0.70 mg/dL; and 1.38 +/- 0.53 mg/dL, respectively (P = .023 and P = .004 vs baseline respectively). Systolic and diastolic blood pressures at delivery were higher than at baseline (134 +/- 19 and 86 +/- 14 mm Hg vs 126 +/- 21 and 79 +/- 13 mm Hg (P = .029 and P = .053, respectively). These values normalized 1 year later (128 +/- 21 and 80 +/- 16). Decreased use of antihypertensive drugs were the cause of poor blood pressure control (1.8 +/- 1.3 vs 0.9 +/- 0.7, P < .01). Blood pressure control improved following delivery. The most frequent complications were preeclampsia (18.9%), intrahepatic cholestasis (13.5%), and urinary tract infections (13.5%). There were five rejection episodes. Seven miscarriages took place and one mole. Eleven pregnancies were uncomplicated. CONCLUSION: Renal transplantation is the best treatment for fertile women with end-stage renal disease who want to become pregnant. However, pregnancy is risky for the mother, fetus, newborn, and allograft.
Asunto(s)
Trasplante de Riñón/fisiología , Complicaciones del Embarazo/fisiopatología , Embarazo/fisiología , Presión Sanguínea , Creatinina/sangre , Parto Obstétrico , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Resultado del Embarazo , Estudios RetrospectivosAsunto(s)
Ciclosporina/farmacocinética , Ciclosporina/uso terapéutico , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Antifúngicos/uso terapéutico , Creatinina/sangre , Ciclosporina/sangre , Interacciones Farmacológicas , Supervivencia de Injerto , Humanos , Inmunosupresores/sangre , Cetoconazol/uso terapéutico , Trasplante de Riñón/patología , Trasplante de Riñón/fisiología , Tasa de Depuración Metabólica , Potasio/sangre , Sodio/sangreAsunto(s)
Trasplante de Riñón/fisiología , Donantes de Tejidos/estadística & datos numéricos , Adulto , Presión Sanguínea , Índice de Masa Corporal , Creatinina/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Estudios de Seguimiento , Hematuria , Humanos , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Proteinuria , Factores de Riesgo , Factores de TiempoRESUMEN
A case of hantavirus pulmonary syndrome (HPS) was serologically confirmed in a critically ill patient in Santiago, Chile. The patient's clinical course had many similarities to that of other HPS patients in North and South America but was complicated by acute severe renal failure. The patient's history included self-reported urban and probable rural rodent exposure during travel in Bolivia. Comparison of a viral sequence from an acute-phase serum sample with other known hantaviruses showed that the hantavirus nucleic acid sequence from the patient was very similar to a virus recently isolated from rodents associated with HPS cases in Paraguay.
Asunto(s)
Síndrome Pulmonar por Hantavirus/virología , Viaje , Adulto , Animales , Bolivia , Chile , Resultado Fatal , Síndrome Pulmonar por Hantavirus/mortalidad , Síndrome Pulmonar por Hantavirus/fisiopatología , Humanos , Masculino , ARN ViralRESUMEN
OBJECTIVE: To determine whether bacteremia can be detected more rapidly and completely by (1) obtaining two blood cultures instead of one and/or (2) collecting a larger volume of blood. STUDY DESIGN: Prospective comparison of different strategies in 300 patients undergoing blood culture for suspected bacteremia. Each patient had two samples of blood, A (2 ml) and B (9.5 ml), obtained sequentially from separate sites. The B sample was divided into three aliquots: B1 (2 ml), B2 (6 ml), and ISO (1.5 ml, quantitative culture). RESULTS: A pathogen was isolated from one or more blood cultures in 30 patients (10% of cases). When measured at 24 hours, the pathogen recovery rate for the B2 sample (72%) was higher than that for the individual small-volume samples (A = 37%, B1 = 33%; p < 0.01 for each comparison) and for the combination of the two small-volume samples (A + B1 = 47%; p = 0.04). At final (7-day) reading the pathogen recovery rate for the B2 sample (83%) was higher than that for B1 (60%; p = 0.02) and similar to the recovery rate observed with the combination of the two small-volume cultures (A + B1 = 73%; p = 0.55). CONCLUSIONS: Increasing the volume of blood inoculated into blood culture bottles improves the timely detection of bacteremia in pediatric patients and spares the patients the cost and pain of an additional venipuncture.
Asunto(s)
Bacteriemia/microbiología , Bacterias/aislamiento & purificación , Adolescente , Bacteriemia/sangre , Bacteriemia/diagnóstico , Bacterias/crecimiento & desarrollo , Técnicas Bacteriológicas , Sangre/microbiología , Recolección de Muestras de Sangre , Niño , Preescolar , Escherichia coli/crecimiento & desarrollo , Escherichia coli/aislamiento & purificación , Haemophilus influenzae/crecimiento & desarrollo , Haemophilus influenzae/aislamiento & purificación , Humanos , Lactante , Flebotomía , Estudios Prospectivos , Salmonella/crecimiento & desarrollo , Salmonella/aislamiento & purificación , Streptococcus pneumoniae/crecimiento & desarrollo , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
Results of urinalysis and culture of 2181 urine specimens obtained by catheter from febrile children aged less than 24 months were analyzed to determine the following: (1) an optimal cutoff point in considering a bacterial colony count clinically "significant," (2) the accuracy of leukocyte esterase and nitrite tests in identification of pyuria and bacteriuria, and (3) the utility of pyuria (defined as > or = 10 leukocytes/mm3) in the discrimination of urinary tract infection from asymptomatic bacteriuria. Among 110 urine cultures with > or = 10,000 colony-forming units per milliliter, 92 (84%) had > or = 100,000 CFU/ml, 10 (9%) had 50,000 to 99,000 CFU/CFU/ml and 8 (7%) had 10,000 to 49,000 CFU/ml. Urine specimens with 1000 to 49,000 CFU/ml were more likely than specimens with > or = 50,000 CFU/ml to yield Gram-positive or mixed organisms (36/60 vs 7/109; p < 0.001). A count of < 10 leukocytes/mm3 was almost invariably associated with a sterile culture; a count of > or = 10 leukocytes/mm3 was found in 93 of 102 patients with > or = 50,000 CFU/ml. The dipstick leukocyte esterase test had sensitivities of 52.9% and 66.7% in detecting > or = 10 leukocytes/mm3 and > or = 20 leukocytes/mm3, respectively. The dipstick nitrite test had a sensitivity of 31.4% in detecting bacteriuria (> or = 50,000 CFU/ml). Acute pyelonephritis was diagnosed by a renal scan with dimercaptosuccinic acid labeled with technetium 99m in 50 (77%) of 65 patients with > or = 10 leukocytes/mm3 but in none of five patients with < 10 leukocytes/mm3 (p < 0.01). The findings in these five patients were consistent with colonization of the urinary tract rather than infection. For urine specimens obtained by catheter, we believe that urinary tract infection is best defined by both a leukocyte count > or 10/mm3 and a CFU count > or = 50,000/ml. This definition almost always discriminates among true urinary tract infection, bacteriuria resulting from contamination of the urine specimen, and asymptomatic bacteriuria.