Asunto(s)
Enfermedades de la Médula Ósea , Estomatitis , Humanos , Metotrexato/efectos adversos , Médula ÓseaAsunto(s)
Toxinas Bacterianas/efectos adversos , Síndrome de Fuga Capilar/inducido químicamente , Exotoxinas/efectos adversos , Síndrome Hemolítico-Urémico/inducido químicamente , Leucemia de Células Pilosas/tratamiento farmacológico , Anciano , Toxinas Bacterianas/uso terapéutico , Síndrome de Fuga Capilar/fisiopatología , Terapia Combinada , Exotoxinas/uso terapéutico , Femenino , Estudios de Seguimiento , Síndrome Hemolítico-Urémico/terapia , Humanos , Leucemia de Células Pilosas/diagnóstico , Metilprednisolona/uso terapéutico , Multimorbilidad , Transfusión de Plaquetas/métodos , Diálisis Renal/métodos , Medición de Riesgo , Resultado del TratamientoAsunto(s)
Hiperpotasemia , Insuficiencia Renal Crónica , Anciano , Humanos , Polímeros , RecurrenciaRESUMEN
Calbindin-D28k (CBD-28k) is a calcium binding protein located in the distal convoluted tubule (DCT) and plays an important role in active calcium transport in the kidney. Loop and thiazide diuretics affect renal Ca and Mg handling: both cause Mg wasting, but have opposite effects on Ca excretion as loop diuretics increase, but thiazides decrease, Ca excretion. To understand the role of CBD-28k in renal Ca and Mg handling in response to diuretics treatment, we investigated renal Ca and Mg excretion and gene expression of DCT Ca and Mg transport molecules in wild-type (WT) and CBD-28k knockout (KO) mice. Mice were treated with chlorothiazide (CTZ; 50 mg · kg(-1) · day(-1)) or furosemide (FSM; 30 mg · kg(-1) · day(-1)) for 3 days. To avoid volume depletion, salt was supplemented in the drinking water. Urine Ca excretion was reduced in WT, but not in KO mice, by CTZ. FSM induced similar hypercalciuria in both groups. DCT Ca transport molecules, including transient receptor potential vanilloid 5 (TRPV5), TRPV6, and CBD-9k, were upregulated by CTZ and FSM in WT, but not in KO mice. Urine Mg excretion was increased and transient receptor potential subfamily M, member 6 (TRPM6) was upregulated by both CTZ and FSM in WT and KO mice. In conclusion, CBD-28k plays an important role in gene expression of DCT Ca, but not Mg, transport molecules, which may be related to its being a Ca, but not a Mg, intracellular sensor. The lack of upregulation of DCT Ca transport molecules by thiazides in the KO mice indicates that the DCT Ca transport system is critical for Ca conservation by thiazides.
Asunto(s)
Calbindina 1/metabolismo , Calcio/metabolismo , Clorotiazida/farmacología , Furosemida/farmacología , Túbulos Renales Distales/efectos de los fármacos , Magnesio/metabolismo , Eliminación Renal/efectos de los fármacos , Inhibidores de los Simportadores del Cloruro de Sodio/farmacología , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacología , Animales , Western Blotting , Calbindina 1/deficiencia , Calbindina 1/genética , Calcio/orina , Canales de Calcio/genética , Canales de Calcio/metabolismo , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Genotipo , Túbulos Renales Distales/metabolismo , Magnesio/orina , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína G de Unión al Calcio S100/genética , Proteína G de Unión al Calcio S100/metabolismo , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismoRESUMEN
The success of organ transplantation allows many transplant recipients to return to life similar to nontransplant patients. Their need for regular health care, including preventive medicine, has switched the majority of responsibilities for their health care from transplant specialists to primary care physicians. To take care of transplant recipients, it is critical for primary care physicians to be familiar with immunosuppressive medications, their side effects, and common complications in transplant recipients. Ten subjects are reviewed here in order to assist primary care physicians in providing optimal care for transplant recipients.
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Monitoreo de Drogas/normas , Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Trasplante de Órganos/efectos adversos , Atención Primaria de Salud/normas , Receptores de Trasplantes , Corticoesteroides/efectos adversos , Corticoesteroides/inmunología , Corticoesteroides/uso terapéutico , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/normas , Ciclosporina/efectos adversos , Ciclosporina/inmunología , Ciclosporina/uso terapéutico , Diarrea/inducido químicamente , Diarrea/complicaciones , Diarrea/inmunología , Interacciones Farmacológicas/inmunología , Monitoreo de Drogas/métodos , Procedimientos Quirúrgicos Electivos/efectos adversos , Procedimientos Quirúrgicos Electivos/normas , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/inmunología , Masculino , Cumplimiento de la Medicación , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/inmunología , Ácido Micofenólico/uso terapéutico , Osteonecrosis/inducido químicamente , Osteonecrosis/tratamiento farmacológico , Policitemia/tratamiento farmacológico , Policitemia/etiología , Embarazo , Complicaciones del Embarazo/inducido químicamente , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/prevención & control , Atención Primaria de Salud/métodos , Sirolimus/efectos adversos , Sirolimus/inmunología , Sirolimus/uso terapéutico , Tacrolimus/efectos adversos , Tacrolimus/inmunología , Tacrolimus/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/etiología , Infecciones Urinarias/inmunologíaRESUMEN
OBJECTIVES: In a multicenter, open-label, treatment protocol (HGT-REP-059; NCT01031173), clinical effects and tolerability of agalsidase alfa (agalα; 0.2 mg/kg every other week) were evaluated in patients with Fabry disease who were treatment naïve or switched from agalsidase beta (switch). Over 24 months, data were collected on the safety profile; renal and cardiac parameters were assessed using estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and midwall fractional shortening (MFS). RESULTS: Enrolled patients included 71 switch (median [range] age, 46.6 [5-84] years; male to female [M:F], 40:31) and 29 treatment naïve (38.7 [12-74] years; M:F, 14:15). Adverse events (AEs) were consistent with the known safety profile of agalα. Two switch patients had hospitalization due to possibly/probably drug-related serious AEs (one with transient ischemic attack, one with infusion-related AEs). One switch and two treatment-naïve patients discontinued treatment because of AEs. Three patients (one each switch, treatment naïve, and previous agalα) died; no deaths were considered drug-related. There was no significant change from baseline in LVMI or MFS in either group. Similarly, eGFR remained stable; mean ± standard error annualized change in eGFR (mL/min/1.73 m(2)) was -2.40 ± 1.04 in switch and -1.68 ± 2.21 in treatment-naïve patients. CONCLUSIONS: This is the largest cohort of patients with Fabry disease who were started on or switched to agalα in an FDA-accepted protocol during a worldwide supply shortage of agalsidase beta. Because this protocol was primarily designed to provide access to agalα, there were limitations, including not having stringent selection criteria and the lack of a placebo group.
RESUMEN
BACKGROUND: Signs and symptoms of the X-linked disorder, Fabry disease (FD), can occur early during childhood with heterogeneous clinical manifestations including potential cardiac and renal dysfunction. Several studies support the efficacy of the enzyme replacement therapy (ERT) agalsidase alfa, in adults with FD, though published data on the long-term safety and efficacy of agalsidase alfa in children are limited. As early treatment with ERT has the potential to reduce complications arising from disease progression, children in particular could benefit. The objective of this study was to evaluate the safety and efficacy of long-term agalsidase alfa ERT in children with FD. METHODS: TKT029 was a 6.5-year open-label, multicenter, extension study of children who completed TKT023 (26-week, open-label, every-other-week, intravenous 0.2 mg/kg agalsidase alfa). TKT029 was divided into two phases (before and after an agalsidase alfa manufacturing process change); only patients who participated in both phases were included in the analysis. Primary endpoints included safety, tolerability, and heart rate variability (HRV). Additional efficacy parameters included left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and plasma/urine globotriaosylceramide (Gb3). RESULTS: Eleven patients participated (phase 1 baseline median [range] age: 10.8 [8.6-17.3] years; 10 [90.9%] males). During TKT029 (6.5 years), all patients experienced ≥1 treatment-emergent adverse event (AE); eight patients had ≥1 possibly/probably drug-related AE. Six patients experienced infusion-related AEs, but none discontinued due to AEs. Eight serious AEs arose (two patients); none were deemed drug-related. No deaths occurred. Three patients developed anti-agalsidase alfa antibodies, with IgG antibodies in one patient that were agalsidase alfa neutralizing, but without apparent clinical impact. Renal (eGFR) endpoints remained generally in normal range. Cardiac endpoints remained stable within normal range for LVMI and a trend towards improved HRV, although some patients experienced a reduction in heart rate. Plasma and urinary Gb3 reductions were maintained. CONCLUSIONS: TKT029 represents the longest assessment of ERT in children with FD in a clinical trial setting. Overall, agalsidase alfa was well tolerated and demonstrated a stabilizing clinical effect. Agalsidase alfa may be a useful clinical therapeutic option for long-term treatment initiated during childhood in patients with FD. TRIAL REGISTRATION: http://ClinicalTrials.gov identifier NCT00084084 .
Asunto(s)
Terapia de Reemplazo Enzimático/métodos , Enfermedad de Fabry/tratamiento farmacológico , alfa-Galactosidasa/uso terapéutico , Adolescente , Niño , Terapia de Reemplazo Enzimático/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Isoenzimas/efectos adversos , Isoenzimas/uso terapéutico , Masculino , Proteínas Recombinantes , Resultado del Tratamiento , alfa-Galactosidasa/efectos adversosRESUMEN
BACKGROUND: Tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) is a diagnosis of exclusion based on the presence of uveitis and acute tubulointerstitial nephritis in the absence of other disease entities known to cause both of these disorders. The proximal tubule is frequently affected by this syndrome, resulting in a wide range of presentations that vary from proteinuria to full picture of Fanconi syndrome. However, distal tubular involvement is not common. CASE REPORT: A 32-year-old female patient presented with polyuria, polydipsia and painful red eyes. Her water deprivation test and desmopressin test results were consistent with nephrogenic diabetes insipidus. Her kidney biopsy showed acute tubulointerstitial nephritis. Her eye exam was consistent with uveitis. To our knowledge, this is the first reported case of nephrogenic diabetes insipidus due to tubulointerstitial nephritis and uveitis syndrome. CONCLUSIONS: Tubulointerstitial nephritis and uveitis syndrome (TINU) syndrome can present with multiple renal tubular defects, including nephrogenic diabetes insipidus.