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BACKGROUND: Metabolomics can be used to identify novel metabolites related to renal function and that could therefore be used for estimating GFR. We evaluated metabolites replicated and related to eGFR in 3 studies (CKD and general population). METHODS: Metabolomics was performed by GC-MS. The Progredir Cohort (nâ¯=â¯454, class 3 and 4 CKD) was used as the derivation study and adjusted linear regression models on eGFR-CKDEPI were built. Bonferroni correction was applied for selecting metabolites to be independently validated in the Diabetic Nephropathy Study (nâ¯=â¯56, macroalbuminuric DN) and in the Baependi Heart Study (BHS, nâ¯=â¯1145, general population). RESULTS: In the Progredir Cohort, 72 metabolites where associated with eGFR. Of those, 11 were also significantly associated to eGFR in the DN Study and 8 in the BHS. Four metabolites were replicated and significantly associated to eGFR in all 3 studies: d-threitol, myo-inositol, 4-deoxierythronic acid and galacturonic acid. In addition, pseudouridine was strongly correlated to eGFR only in the 2 CKD populations. CONCLUSIONS: Our results demonstrate metabolites that are potential biomarkers of renal function: d-threitol, myo-inositol, 4-deoxierythronic acid, galacturonic acid and pseudouridine. Further investigation is needed to determine their performance against otherwise gold-standard methods, most notably among those with normal eGFR.
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Tasa de Filtración Glomerular , Metabolómica , Insuficiencia Renal Crónica/metabolismo , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatologíaAsunto(s)
Eliminación de Componentes Sanguíneos/métodos , Preeclampsia/diagnóstico , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Biomarcadores/sangre , Femenino , Humanos , Proteínas de la Membrana/sangre , Proyectos Piloto , Preeclampsia/clasificación , Embarazo , Ultrasonografía PrenatalRESUMEN
BACKGROUND AND AIMS: 1,25(OH)2Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown. METHODS AND RESULTS: Eighty-eight stage G3-4 CKD patients randomly received 2 µg paricalcitol (PCT)/day (n = 44) or placebo (n = 44) for 12 weeks. Sclerostin, a major AGE compound like pentosidine, and bone mineral disorder biomarkers were measured at baseline, at 12 weeks and 2 weeks after stopping the treatments. At baseline, in the whole study population sclerostin correlated with male gender (P = 0.002), BMI (P < 0.001), waist circumference (P < 0.001), serum pentosidine (P = 0.002) and to a weaker extent, with diabetes (P = 0.04), 1,25(OH)2Vitamin D (r = 0.22, P = 0.04) and serum phosphate (r = -0.26, P = 0.01). Sclerostin increased during PCT treatment (average + 15.7 pg/ml, 95% CI: -3.0 to +34.3) but not during placebo (P = 0.03) and the PCT effect was abolished 2 weeks after stopping this drug. The increase in sclerostin levels induced by PCT was modified by prevailing pentosidine levels (P = 0.01) and was abolished by statistical adjustment for simultaneous changes in PTH but not by FGF23 changes. CONCLUSIONS: VDRA by paricalcitol causes a moderate increase in serum sclerostin in CKD patients. Such an effect is abolished by adjustment for PTH, suggesting that it may serve to counter PTH suppression. The sclerostin rise by PCT is attenuated by pentosidine, an observation in keeping with in vitro studies showing that AGEs alter the functioning of the VDRA.
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Arginina/análogos & derivados , Proteínas Morfogenéticas Óseas/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/tratamiento farmacológico , Ergocalciferoles/administración & dosificación , Lisina/análogos & derivados , Insuficiencia Renal Crónica/tratamiento farmacológico , Vitaminas/administración & dosificación , Proteínas Adaptadoras Transductoras de Señales , Anciano , Arginina/sangre , Biomarcadores/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , Método Doble Ciego , Ergocalciferoles/efectos adversos , Femenino , Factor-23 de Crecimiento de Fibroblastos , Marcadores Genéticos , Humanos , Italia , Lisina/sangre , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/metabolismo , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Vitaminas/efectos adversosRESUMEN
BACKGROUND AND AIMS: Vitamin D receptor activation (VDRA) ameliorates endothelial dysfunction in CKD patients but also increases phosphate and FGF-23, which may attenuate the beneficial effect of VDRA on endothelial function. METHODS AND RESULTS: This is a pre-specified secondary analysis of the PENNY trial (NCT01680198) testing the effect of phosphate and FGF-23 on the flow mediated vasodilatory (FMD) response to paricalcitol (PCT, 2 µg/day) and placebo over a 12-weeks treatment period. Eighty-eight stage G3-4 CKD patients were randomized to PCT (n = 44) and Placebo (n = 44). Endothelial function was assessed by measuring endothelium dependent forearm blood flow (FBF) response to ischemia. The FMD response was by the 61% higher in PCT treated patients than in those on placebo (P = 0.01). Phosphate (+11%, P = 0.039), calcium (+3%, P = 0.01) and, particularly so, FGF23 (+164%, P < 0.001) increased in PCT treated patients. Changes in FMD by PCT associated inversely with phosphate (r = -0.37, P = 0.01) but were independent of FGF-23, calcium and PTH changes. The response to PCT was maximal in patients with no changes in phosphate (1st tertile), attenuated in those with mild-to-moderate rise in phosphate (2nd tertile) and abolished in those with the most pronounced phosphate increase (3rd tertile) (effect modification P = 0.009). No effect modification by FGF-23 and other variables was observed. CONCLUSIONS: The beneficial effect of PCT on endothelial function in CKD is maximal in patients with no or minimal changes in phosphate and it is abolished in patients with a pronounced phosphate rise. These findings generate the hypothesis that the endothelium protective effect by VDRA may be potentiated by phosphate lowering interventions.
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Arteria Braquial/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Ergocalciferoles/uso terapéutico , Antebrazo/irrigación sanguínea , Fosfatos/sangre , Receptores de Calcitriol/agonistas , Insuficiencia Renal Crónica/tratamiento farmacológico , Vasodilatación/efectos de los fármacos , Vasodilatadores/uso terapéutico , Anciano , Biomarcadores/sangre , Arteria Braquial/metabolismo , Arteria Braquial/fisiopatología , Método Doble Ciego , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Ergocalciferoles/efectos adversos , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/metabolismo , Flujo Sanguíneo Regional , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Resultado del Tratamiento , Vasodilatadores/efectos adversosRESUMEN
INTRODUCTION: Preeclampsia is a disorder related to an imbalance in the angiogenesis axis manifesting as endothelial dysfunction. Animal and human studies have shown that sFLT-1 (soluble fms like tyrosine kinase 1) is increased and PlGF (placental growth factor) reduced during the disease state. There are a paucity of studies investigating the clinical significance of normalising angiogenic axis. OBJECTIVES: To use a non-human primate uteroplacental ischemic (UPI) model of preeclampsia to assess if reversing the angiogenic imbalance, by increasing circulating PlGF, is able to ameliorate the hypertension and proteinuria. METHODS: Hypertensive proteinuria was induced in a non-human primate (Papio hamadryas) by ligation of a unilateral uterine artery at 130days of an 182day pregnancy. After two weeks of UPI, PlGF was administered by subcutaneous injection (100mg/kg/day) for 5 days (n=3) or normal saline in an equivalent volume (n=3). Blood pressure was monitored via intra-arterial radiotelemetry, sFLT-1 measured via ELISA and spot urinary protein:creatinine ratios were measured to monitor proteinuria. Data was analysed using SPSS by t-tests and analysis of repeated measures. Significance was set at p<0.05 and data expressed as the mean ±SEM. RESULTS: After two weeks of UPI both groups demonstrated a significant elevation in blood pressure, proteinuria (p<0.05) and sFLT-1 (p<0.001). The systolic BP increased by 12.4±2.3mmHg and 11.7±2.9mmHg in the PlGF and control groups respectively compared to baseline (p<0.005). After PlGF administration, there was a significant reduction in blood pressure in the treated group (-5.2s±0.8mmHg) compared to the increase in BP in the control group (+6.5±3mmHg). Proteinuria also reduced in the treated group from 112±51mg/mmol to 38±12mg/mmol whilst proteinuria in the control group was unchanged. The total circulating sFLT-1 was not significantly affected by the administration of PlGF after 5days. Although this study was not designed to assess fetal safety or outcomes, there was no adverse fetal outcome attributable to the administration of the PlGF. CONCLUSION: Administration of PlGF resulted in a reduction in BP and proteinuria without significantly affecting total sFLT-1 levels. Correcting the angiogenic axis imbalance may improve the clinical parameters in a non-human primate animal model of preeclampsia.
RESUMEN
In uncomplicated pregnancies, first trimester androgen, oestrogen and prolactin concentrations were higher in nulliparous (n=160) than parous (n=260) mothers. Androgens and estrogens were higher in younger than older mothers. These data are consistent with elevated hormone concentrations mediating the breast cancer protection from a first pregnancy and pregnancies occurring at younger ages.
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Hormonas Esteroides Gonadales/sangre , Primer Trimestre del Embarazo , Femenino , Humanos , EmbarazoRESUMEN
Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. To investigate the relation between blood levels of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) with hemodialysis outcomes, we measured baseline vitamin D levels in a cross-sectional analysis of 825 consecutive patients from within a prospective cohort of incident US hemodialysis patients. Of these patients, 78% were considered vitamin D deficient with 18% considered severely deficient. Calcium, phosphorus, and parathyroid hormone levels correlated poorly with 25D and 1,25D concentrations. To test the association between baseline vitamin D levels and 90-day mortality, we selected the next 175 consecutive participants who died within 90 days and compared them to the 750 patients who survived in a nested case-control analysis. While low vitamin D levels were associated with increased mortality, significant interaction was noted between vitamin D levels, subsequent active vitamin D therapy, and survival. Compared to patients with the highest 25D or 1,25D levels who received therapy, untreated deficient patients were at significantly increased risk for early mortality. Our study shows that among incident hemodialysis patients, vitamin D deficiency is common, correlates poorly with other components of mineral metabolism and is associated with increased early mortality.
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Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Diálisis Renal/mortalidad , Deficiencia de Vitamina D/complicaciones , Vitamina D/metabolismo , Anciano , Calcio/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Hiperparatiroidismo/tratamiento farmacológico , Hiperparatiroidismo/etiología , Hiperparatiroidismo/metabolismo , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Hormona Paratiroidea/metabolismo , Fósforo/metabolismo , Estudios Prospectivos , Factores de Riesgo , Análisis de Supervivencia , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/metabolismoRESUMEN
The soluble VEGF receptor, sFlt-1 (otherwise referred to as sVEGFR-1), has been implicated in the pathogenesis of preeclampsia. The preeclamptic placenta has been previously demonstrated to produce high levels of the soluble VEGF receptor. Here we tested the hypothesis that peripheral blood mononuclear cells (PBMCs) may also represent an additional source for circulating sFlt-1 during normal and preeclamptic pregnancies. We first demonstrate that preeclamptic placentae show five-fold increased Flt-1 and sFlt-1 mRNA levels. We also show that the Flt-1 and sFlt-1 levels are eight-fold higher in preeclamptic placentae if we collect biopsies without rinsing them in saline to remove excess blood. Cultured villous explants from women with preeclampsia failed to show the increased amount of Flt-1 and sFlt-1 mRNA that was observed in the placental biopsies of normal pregnancy and preeclampsia. Under normoxic conditions the Flt-1 and sFlt-1 mRNA levels in the explants were 3.11+/-0.6 fold in normal pregnancy and 3.6+/-0.4 fold in women with preeclampsia (p = NS by ANOVA). However, the same villous explants showed hypoxic induction of Flt-1 mRNA (NP 3.96+/-0.4 fold, p = NS and PE 5.24+/-0.6 fold, p < 0.05 by ANOVA). We analyzed Flt-1 and sFlt-1 protein levels in the peripheral blood mononuclear cells (PBMCs) to analyze the possibility of an extra-placental sFlt-1 source. Our results indicate that PBMCs of pregnant women are capable of expressing variable amounts of Flt-1 proteins. PBMCs from pregnant women exposed to hypoxia show up-regulation of HIF-1alpha and Flt-1 proteins. PBMCs obtained from women with preeclampsia (n = 9) produced significantly higher amounts of sFlt-1 under normal tissue culture conditions (104.6+/-14.3 pg/ml vs. 46.23+/-5.03 pg/ml, p < 0.05 by ANOVA) and much higher concentrations under hypoxia (196.74+/-26.3pg/ml vs. 83.3+/-13.6pg/ml, p < 0.05 by ANOVA) than PBMCs from normal pregnant women (n = 11). Moreover, analysis of PBMCs from a different group of women with a history of preeclampsia showed persistent abnormality of Flt-1 women one year post-partum. The present study indicates that Flt-1 dysregulation in PBMCs of pregnant women resulting in over-expression of sFlt-1 could be an additional (extra-placental) source of sFlt-1 that contributes to the pathogenesis of preeclampsia.
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Leucocitos Mononucleares/metabolismo , Placenta/metabolismo , Preeclampsia/sangre , Embarazo/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Presión Sanguínea , Hipoxia de la Célula/fisiología , Células Cultivadas , Vellosidades Coriónicas/metabolismo , Proteínas de Unión al ADN/metabolismo , Femenino , Expresión Génica , Edad Gestacional , Humanos , Factor 1 Inducible por Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteínas Nucleares/metabolismo , Placenta/patología , ARN Mensajero/metabolismo , Factores de Transcripción/metabolismo , Regulación hacia Arriba , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVE: Systemic inflammation might contribute to the pathogenesis of preeclampsia. In addition, the association between obesity and inflammation in preeclampsia has not been examined in detail. We determined whether first-trimester elevation of serum C-reactive protein, an index of systemic inflammation, was associated with preeclampsia. METHODS: We conducted a prospective, nested case-control study among women enrolled in the Massachusetts General Hospital Obstetrical Maternal Study cohort. High-resolution C-reactive protein assays were performed on first-trimester (11 +/- 2 weeks' gestation) serum samples in 40 women in whom preeclampsia developed (blood pressure [BP] greater than 140/90 mmHg, and proteinuria, either 2+ or more by dipstick or greater than 300 mg per 24 hours), and in 80 matched controls. This sample size had greater than 80% power to detect a difference in C-reactive protein levels between cases and controls. We used nonparametric tests to compare C-reactive protein levels and conditional logistic regression to control for confounding variables. RESULTS: First-trimester C-reactive protein levels were significantly higher among women in whom preeclampsia subsequently developed compared with controls (4.6 compared with 2.3 mg/L, P =.04). When women were subdivided into C-reactive protein quartiles, the odds ratio (OR) of being in the highest quartile of C-reactive protein was 3.2 (95% confidence interval [CI] 1.1, 9.3, P =.02) among cases of preeclampsia compared with controls. When body mass index (BMI) was added to the multivariable model, the highest quartile of C-reactive protein was no longer associated with increased risk of preeclampsia (OR 1.1, 95% CI.3, 4.3, P =.94). In the same model without BMI, the highest quartile of C-reactive protein was associated with increased risk of preeclampsia (OR 3.5, 95% CI 1.3, 9.5, P =.01). CONCLUSION: In women with preeclampsia, there was evidence of increased systemic inflammation in the first trimester. Inflammation might be part of a causal pathway through which obesity predisposes to preeclampsia.
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Proteína C-Reactiva/análisis , Obesidad/epidemiología , Preeclampsia/epidemiología , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Obesidad/sangre , Paridad , Preeclampsia/sangre , Preeclampsia/etiología , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: To find whether pulse pressure, a measure of arterial compliance, is associated early in pregnancy with increased risk of developing preeclampsia. METHODS: In a prospective cohort of 576 nulliparas, we examined blood pressures throughout pregnancy and at 6-8 weeks postpartum. Measurements during weeks 7-15, 16-24, and 25-38 of gestation were pooled to find averages for each period. Outcomes assessed were gestational hypertension and preeclampsia. Logistic regression analysis was used to develop relative risks and 95% confidence intervals. RESULTS: We confirmed 34 (5.9%) cases of preeclampsia, 32 (5.6%) cases of gestational hypertension, and 510 normotensive women. Mean systolic and diastolic blood pressures and mean arterial pressures were elevated throughout pregnancy in women who developed hypertensive disorders of pregnancy compared with normotensive women. Pulse pressure at 7-15 weeks was significantly higher in women who developed preeclampsia (45 +/- 6 mmHg) than in those who developed gestational hypertension (41 +/- 7 mmHg, P =.03) and normotensive women (41 +/- 8 mmHg, P =.01). Examined in tertiles, increasing pulse pressure was associated with increasing risk of developing preeclampsia (P for trend =.01) but not gestational hypertension (P for trend =.95). After adjustment for potential confounders, a 1-mmHg rise in early pregnancy pulse pressure was associated with a 6% (95% confidence interval: 1, 10) increase in risk for developing preeclampsia but not gestational hypertension (relative risk: 1%; 95% confidence interval: -1, 6). Beyond 15 weeks' gestation, differences between groups diminished, but women with any hypertensive disorder had higher pulse pressures than women with uncomplicated pregnancies. CONCLUSION: Elevated pulse pressure, indicating poor arterial compliance, was evident early in pregnancies of women who subsequently developed preeclampsia.
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Presión Sanguínea , Hipertensión/fisiopatología , Preeclampsia/fisiopatología , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Hipertensión/diagnóstico , Modelos Logísticos , Preeclampsia/diagnóstico , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Diagnóstico Prenatal , Estudios Prospectivos , Flujo Pulsátil , Factores de RiesgoRESUMEN
OBJECTIVE: To examine the relationship between pregravid body mass index (BMI), elevated cholesterol level, and the development of hypertensive disorders of pregnancy. METHODS: We studied 15,262 women who gave birth between 1991 and 1995. Pregravid exposures including BMI and self-reported history of elevated cholesterol were ascertained by biennial mailed questionnaires. Gestational hypertension or preeclampsia was confirmed by medical record review according to standard criteria. Proportional hazards analysis was used to adjust for potential confounding variables. RESULTS: We confirmed 216 cases of gestational hypertension and 86 cases of preeclampsia. The risk of gestational hypertension increased as pregravid BMI increased (P < .01). Compared with women with a pregravid BMI of 21-22.9 kg/m2, the relative risk (RR) of gestational hypertension was 1.6 (95% confidence interval [CI] 1.0, 2.3) for women with BMI of 23-24.9 kg/m2, 2.0 (95% CI 1.3, 3.0) for BMI 25-29.9 kg/m2, and 2.6 (95% CI 1.6, 4.4) for BMI over 30 kg/m2. Leaner women (BMI less than 21 kg/m2) had a reduced risk (RR 0.7, 95% CI 0.4, 1.0). For preeclampsia, the RR of women with pregravid BMI over 30 kg/m2 was 2.1 (95% CI 1.0, 4.6) (P for trend 0.09). A history of elevated cholesterol was not associated with the risk of gestational hypertension (RR 0.9, 95% CI, 0.6, 1.4). In contrast, the RR of preeclampsia in women with a history of elevated cholesterol was 2.0 (95% CI 1.2, 3.3). CONCLUSION: Pregravid BMI and hypercholesterolemia could identify women at higher risk for hypertensive disorders during pregnancy.
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Índice de Masa Corporal , Hipercolesterolemia/complicaciones , Hipertensión/etiología , Preeclampsia/etiología , Complicaciones Cardiovasculares del Embarazo/etiología , Complicaciones Hematológicas del Embarazo , Adulto , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Preeclampsia/epidemiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Estudios Prospectivos , Riesgo , Factores de RiesgoRESUMEN
Oral contraceptive use is associated with hypertension, dyslipidemias, and insulin resistance, all of which also characterize hypertensive disorders of pregnancy. In this prospective cohort study, the association of oral contraceptive use before pregnancy and the risk of gestational hypertension and preeclampsia was assessed. Between 1991 and 1995, 3973 nulliparous women who reported their first pregnancy lasting > or = 6 months were studied. Pregravid exposures were collected by biennial mailed questionnaires, and cases were confirmed by medical record review. Recent oral contraceptive use was defined as use within 2 years of pregnancy. Proportional hazards analysis was used to adjust for potential confounding variables. During the 4 years of follow-up, 133 (3.3%) women with gestational hypertension and 62 (1.6%) with preeclampsia were identified. Twenty-five percent of women who did not develop these disorders were recent users of oral contraceptives, compared with 19% (p = 0.11) of women who developed gestational hypertension and 30% (p = 0.38) who developed preeclampsia. Mean duration of prior oral contraceptive use was similar for cases and noncases. Compared with never and past users, the multivariate relative risk among recent users for developing gestational hypertension was 0.7 (95% confidence interval (CI), 0.4-1.0) and for preeclampsia was 1.3 (95% CI, 0.8-2.4). Among recent users who had used oral contraceptives for > or = 8 years, the relative risk for gestational hypertension was 0.6 (95% CI, 0.3-1.2) and for preeclampsia was 2.1 (95% CI, 1.1-4.2). When the analysis was restricted to women who had never smoked, the risk for gestational hypertension was 0.2 (95% CI, 0.1-0.9) and for preeclampsia was 4.1 (95% CI, 1.9-8.7). Thus, recent use of oral contraceptives was associated with a reduced risk for developing gestational hypertension. In contrast, there was a suggestion that recent use was associated with an increased risk of developing preeclampsia, but only among women who had used these agents for > or = 8 years.
PIP: This article presents a prospective study on the relationship between pregravid oral contraceptive use and the risk of pregnancy-related hypertensive disorders. Oral contraceptives have been known to increase the risk to hypertension, dyslipidemias and insulin resistance, which characterize hypertensive disorders of pregnancy. This study examines this presumption by employing 3973 nulliparous women with pregnancies lasting 6 months during 1991-95. Data were taken from the results of biennial questionnaires and examination of prenatal records. Follow-up for the past 4 years identified 133 (3.3%) women with gestational hypertension and 62 (1.6%) with preeclampsia. Recent oral contraceptive use within 2 years of pregnancy was inversely associated with the development of gestational hypertension but was directly associated with preeclampsia. Compared with never users and past users, multivariate relative risk among recent users for the development of gestational hypertension was 0.7 (95% CI, 0.4-1.0) and of preeclampsia was 1.3 (95% CI, 0.8-2.4). Recent use of oral contraceptives (8 or more years) predisposes to a 0.6 risk for gestational hypertension and a 2.1 risk for preeclampsia. Thus, recent use of oral contraceptives was associated with a reduced risk for developing gestational hypertension. In contrast, there was a suggestion that recent use was associated with an increased risk of developing pre-eclampsia, but only among women who had used these agents for 8 or more years.
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Anticonceptivos Orales/efectos adversos , Hipertensión/etiología , Preeclampsia/etiología , Complicaciones Cardiovasculares del Embarazo , Adulto , Estudios de Cohortes , Anticonceptivos Orales/administración & dosificación , Femenino , Humanos , Análisis Multivariante , Embarazo , Estudios Prospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
PURPOSE: The intra-aortic balloon pump has become an important tool in the management of patients with severe coronary artery disease. Although pump-induced thrombocytopenia was described more than 20 years ago, there has been no prospective study of this condition. PATIENTS AND METHODS: In a prospective study of consecutive adult intensive care patients admitted with acute coronary syndromes, we compared serial platelet counts in 58 patients treated with an intra-aortic balloon pump with 51 patients who were not. All patients received intravenous heparin. RESULTS: Clinical characteristics of the two groups were similar, except that unstable angina was more frequent among balloon pump patients. On each of 6 consecutive days, the mean platelet counts of patients treated with a balloon pump were significantly lower than those of non-pump patients. Platelet counts (mean +/- SD) of balloon pump patients decreased to a nadir of 63% +/- 4% of the initial count on day 4, but subsequently stabilized. There was only a slight, transient decrease in the platelet counts of non-pump patients. Overall, 47% of balloon pump patients developed thrombocytopenia (platelet count <150,000/mm3) compared with 12% of non-pump patients (P <0.01). Platelet counts dropped by at least half of initial counts in 26% of balloon pump patients compared with 4% of non-pump patients (P <0.01). Multivariate analysis demonstrated that the use of an intra-aortic balloon pump was independently associated with a substantial (> or =50%) decline in platelet count (odds ratio 7.2, 95% confidence interval 1.4 to 40, P = 0.03). Removal of the balloon pump was associated with a rapid increase in platelet count. CONCLUSIONS: The use of an intra-aortic balloon pump led to a steady and predictable decrease in platelet count, which recovered rapidly if the balloon pump was removed or slowly if the device remained in place.
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Contrapulsador Intraaórtico/efectos adversos , Trombocitopenia/etiología , Anciano , Cuidados Críticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Prospectivos , Trombocitopenia/sangreRESUMEN
BACKGROUND: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. METHODS: We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. RESULTS: A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. CONCLUSIONS: Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.
Asunto(s)
Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Boston , Dieta , Femenino , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Factores de Riesgo , Luz Solar , Vitamina D/administración & dosificación , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
BACKGROUND: Hepatic artery thrombosis (HAT) remains a devastating complication after liver transplantation. Various factors have been implicated in the pathogenesis of HAT, such as clotting abnormalities, increased hematocrit, and technical complications, but the role of anticardiolipin antibodies has not been evaluated. We investigated the possible association between HAT and anticardiolipin antibodies in adult patients who underwent liver transplantation. METHODS: Seven patients with HAT after orthotopic liver transplantation, 28 liver recipients without HAT, and 35 normal blood donors were evaluated. Determination of IgM and IgG anticardiolipin antibodies was performed by enzyme-linked immunosorbent assay using pretransplant serum from all allograft recipients. Clinical information was obtained from chart review. Fisher's exact test and Wilcoxon rank sum test were used for statistical analysis, and all P-values were two-tailed. RESULTS: Overall, 22 of 35 (63%) liver recipients had a positive anticardiolipin antibody test (either IgG or IgM titer >4 SD from the normal controls). The test was positive in 7 liver recipients (100%) with HAT compared with 15 out of 28 patients (54%) without HAT (P=0.031). As compared with liver recipients without HAT, patients with HAT also tended to have a higher mean anticardiolipin titer of IgG and IgM and a lower pretransplant platelet count; however, these differences were not significant. CONCLUSIONS: Our findings indicate that anticardiolipin antibodies are frequently elevated in patients with liver failure and may contribute to the pathogenesis of HAT after liver transplantation. Other potential consequences of anticardiolipin antibodies in end-stage liver disease remain to be determined.
Asunto(s)
Cardiolipinas/inmunología , Arteria Hepática , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Trasplante de Hígado/efectos adversos , Trombosis/sangre , Trombosis/etiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In recent years, hepatitis C virus infection has been reported to be typically associated with membranoproliferative glomerulonephritis and less frequently with membranous nephropathy. Treatment of hepatitis C with interferon-alpha can reduce viremia and improve renal disease. After liver transplantation for hepatitis C virus-associated liver failure, standard immunosuppressive protocols result in a significant increase in hepatitis C viremia. In this report we describe a patient with end-stage liver disease and biopsy-proven hepatitis C-associated glomerulonephritis who underwent liver transplantation. Within 1 month after transplantation, he developed a severe nephrotic syndrome that paralleled a marked increase in viremia. We discuss the possible pathogenic relationship between hepatitis C virus infection and the nephrotic syndrome that followed liver transplantation.
Asunto(s)
Glomerulonefritis/complicaciones , Hepatitis C/complicaciones , Trasplante de Hígado , Síndrome Nefrótico/etiología , Complicaciones Posoperatorias , Viremia/complicaciones , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Creatinina/sangre , Enalapril/uso terapéutico , Femenino , Glomerulonefritis/virología , Hepacivirus/aislamiento & purificación , Hepatitis C/cirugía , Hepatitis C/terapia , Humanos , Trasplante de Riñón , Trasplante de Hígado/fisiología , Persona de Mediana Edad , Proteinuria , ARN Viral/sangre , Reoperación , Factores de TiempoRESUMEN
BACKGROUND: Primary and secondary forms of focal segmental glomerulosclerosis (FSGS) are common causes of glomerular proteinuria. Secondary forms of FSGS seem to be the result of adaptive changes that follow a reduction in renal mass. We saw an elderly patient with severe bilateral renal vascular disease (RVD) who had FSGS on percutaneous biopsy. To find out whether elderly patients with atherosclerotic RVD are predisposed to the development of FSGS, we reviewed all cases of FSGS at our institution between 1990 and 1995. METHODS: We identified 59 cases of biopsy-proven FSGS and examined clinical, histological, and radiographic records. FINDINGS: Of the 59 patients, 24 were older than 50 years; eight of these had RVD. No patient under the age of 50 had RVD. Seven of the eight patients with RVD and FSGS had substantial proteinuria at presentation. All had typical glomerular lesions with focal segmental tuft collapse and synechiae; other glomeruli were hypertrophic. All patients showed further decline in renal function on follow-up. INTERPRETATION: The association of FSGS and RVD may represent an under-recognised aetiology of significant proteinuria in elderly patients.