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OBJECTIVE: Chronic kidney disease (CKD) pregnancies are at high risk of developing adverse outcomes. In non-pregnant subjects with CKD, higher urinary IgM levels are associated with poor renal survival and higher rates of cardiovascular deaths. In this study, we assessed whether urinary IgM levels are associated with an increased risk of adverse pregnancy outcomes (APO) in CKD pregnancies. METHODS: We performed a nested case-control study within a cohort of CKD patients with singleton pregnancies attended at a tertiary care hospital. The study included 90 CKD patients who eventually developed one or more APO and 77 CKD patients who did not. Urinary IgM excretion was determined from the 24-h urine samples at enrollment by an ultrasensitive enzyme immunoassay. RESULTS: The risk for combined APO and for preeclampsia (PE) was higher among women with urinary IgM and proteinuria levels values in the highest quartile or with CKD stages 4-5 (odds ratios, OR ≥ 2.9), compared with the lowest quartile or with CKD stage 1. Urinary IgM levels were more closely associated with the risk of either combined or specific APO (PE, preterm birth, and for having a small-for-gestational-age infant; OR ≥ 5.9) than either the degree of total proteinuria or CKD stages. Among patients with CKD stage 1, the risk of combined APO, PE, and preterm birth was higher in women with urinary IgM levels values in the highest quartile (OR ≥ 4.8), compared with the three lower quartiles, independently of proteinuria. CONCLUSION: In CKD pregnancies, at the time of initial evaluation, proteinuria and CKD stage are associated with increased risk of combined APO. However, urinary IgM concentrations appear to be better predictors of an adverse outcome and may be useful for risk stratification in CKD pregnancies.
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Imunoglobulina M/urina , Complicações na Gravidez/etiologia , Proteinúria/diagnóstico , Eliminação Renal , Insuficiência Renal Crônica/diagnóstico , Adulto , Biomarcadores/urina , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia/etiologia , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Nascimento Prematuro/etiologia , Proteinúria/etiologia , Proteinúria/urina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/urina , Medição de Risco , Fatores de Risco , Urinálise , Adulto JovemRESUMO
Aim. To determine the frequency of macroprolactinemia, its etiology, and the clinical manifestations in patients with hyperprolactinemia presenting with menstrual irregularities, galactorrhea, and/or infertility who were attended by the gynecology-endocrinology service. Methods. In a cross-sectional study, 326 hyperprolactinemic women were tested for serum prolactin (PRL) concentrations before and after chromatographic separation (gel filtration and affinity with protein G) and extraction of free PRL with polyethylene glycol (PEG). Results. Sera from 57 patients (17.5%) were found to have macroprolactinemia. The presence of macroprolactinemia was attributable to anti-PRL autoantibodies in 54 (94.7%) patients. The median serum PRL levels were similar in patients with or without macroprolactinemia (42.0 versus 38.1 ng/mL). In contrast, patients with macroprolactinemia had lower serum-free PRL levels (median 9.2 versus 31.7 ng/mL, P < 0.001). Patients without macroprolactinemia had a higher frequency of galactorrhea and abnormal pituitary imagine findings (P < 0.002). Conclusions. We can conclude that macroprolactinemia should be considered as a benign variant, and it must be ruled out in women presenting with menstrual irregularities, galactorrhea, and/or infertility in order to investigate other causes different than hyperprolactinemia. Serum PRL precipitated with PEG is a convenient and simple procedure to screen for the presence of macroprolactinemia.
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Preeclampsia is characterized by an imbalance in angiogenic factors. Urinary prolactin (PRL) levels and its antiangiogenic PRL fragments have been associated with disease severity. In this study, we assessed whether these biomarkers are associated with an increased risk of adverse maternal and perinatal outcomes in preeclamptic women. We studied 501 women with preeclampsia attended at a tertiary care hospital. Serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), as well as urinary PRL levels, were measured by enzymed-linked immunosorbent assay. Antiangiogenic PRL fragments were determined by immunoblotting. The risk for any adverse maternal outcome and for having a small-for-gestational-age infant was higher among women with sFlt-1/PlGF ratios, sEng, and urinary PRL level values in the highest quartile (odds ratios ≥ 2.7), compared with the lowest quartile. Both urinary PRL levels and the presence of antiangiogenic PRL fragments were more closely associated with the risk of specific adverse maternal outcomes (placental abruption, hepatic hematoma or rupture, acute renal failure, pulmonary edema, maternal death, and need for endotracheal intubation, positive inotropic drug support, and hemodialysis; odds ratios ≥ 5.7 and ≥ 4.7, respectively) than either sFlt-1/PlGF ratio or sEng alone. We concluded that in preeclamptic women at the time of initial evaluation, sFlt-1/PlGF ratio and sEng are associated with increased risk of combined adverse maternal outcomes. However, urinary PRL concentrations and its antiangiogenic fragments appear to be better predictors of an adverse maternal outcome and may be useful for risk stratification in preeclampsia.
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Antígenos CD/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/metabolismo , Proteínas da Gravidez/sangue , Prolactina/urina , Receptores de Superfície Celular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Injúria Renal Aguda/epidemiologia , Adulto , Biomarcadores/metabolismo , Endoglina , Feminino , Humanos , Morte Materna , Fator de Crescimento Placentário , Valor Preditivo dos Testes , Gravidez , Prognóstico , Edema Pulmonar/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: The etiology of uterine leiomyomatosis is multifactorial and it is unknown if a relation between anti-Müllerian hormone (hormona anti-mülleriana) and uterine leiomyomatosis exists. OBJECTIVE: To determine the differences of hormona anti-mülleriana levels in women with and without uterine leiomyomatosis. METHODS: 60 women were studied (30 with and 30 without uterine leiomyomatosis). The diagnosis was confirmed by histopathology. Both groups were paired by age and in all them serum levels of hormona antimülleriana were measured using ELISA, also estradiol and progesterone serum levels were determined. hormona anti-mülleriana-RII immunohistochemistry was done in healthy myometrium and in leiomyomas. RESULTS: The mean age between the groups didn't show statistical difference (41.8 +/- 5.6 years vs. 41.4 +/- 5.7 years). Also no differences were found in weight, height and body mass index. Serum levels of hormona antimülleriana were lower in those with leiomyomatosis [0.21 (0-10.4) ng/ml vs. 1.83 (0-6.38) ng/ml, p < 0.005]. No statistical differences were found in estradiol and progesterone serum levels between the groups. The hormona antimülleriana receptor was no expressed neither in the healthy myometrium nor in the leiomyomas. CONCLUSIONS: Women with leiomyomatosis had lower hormona antimülleriana levels. More studies are needed to determine if a relation exists between hormona antimülleriana and uterine leiomyomas.
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Hormônio Antimülleriano/sangue , Leiomioma/sangue , Neoplasias Uterinas/sangue , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Estradiol/sangue , Feminino , Humanos , Leiomioma/patologia , Pessoa de Meia-Idade , Progesterona/sangue , Receptores de Peptídeos/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: Preeclampsia is characterized by an imbalance in angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). We herein assessed whether these factors measured by a newly developed automated electrochemiluminescence immunoassay are associated with risk to develop preeclampsia. METHODS: We performed a nested case-control study within a cohort of 230 women with singleton pregnancies. The study included all 37 women who eventually developed preeclampsia and 29 normotensive controls. Serum samples were collected at 4-week intervals (from weeks 20th to 36th). sFlt-1 and PlGF were measured using a commercial automated immunoassay (Elecsys). RESULTS: Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 levels and sFlt-1/PlGF ratio than women with normal pregnancies. These changes became significant at 20 weeks in women destined to develop early preeclampsia (<34 weeks, Pâ ≤ â0.003), and at 24-28 weeks in women who later developed preeclampsia (Pâ ≤â 0.024). The risk for developing preeclampsia was higher among women with PlGF concentration values in the lowest quartile or with sFlt-1 levels and sFlt-1/PlGF ratio in the highest quartile of the control distribution. The odds ratios were higher and appeared earlier in women destined to develop early preeclampsia than in women who presented preeclampsia later. The sFlt-1/PlGF ratio was more tightly associated with risk of preterm or term preeclampsia than either angiogenic factor alone. CONCLUSION: Changes in circulating concentrations of PlGF, sFlt-1, and in the sFlt-1/PlGF ratio precede the onset of preeclampsia. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested at preterm or term.
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Pré-Eclâmpsia/sangue , Proteínas da Gravidez/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Proteínas Angiogênicas/sangue , Automação , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Imunoensaio , Medições Luminescentes , Fator de Crescimento Placentário , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/etiologia , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Fatores de Risco , SolubilidadeRESUMO
OBJECTIVE: Recent studies have demonstrated that stimulating autoantibodies against the angiotensin II type 1 receptor (AT1R-AA) are frequently detected in the sera from women with preeclampsia, suggesting that they may play an important role in the pathogenesis of this disease. Nevertheless, the real clinical significance of AT1R-AA in preeclampsia is still controversial due to the paucity of appropriate large comparative studies that require cumbersome, time-consuming, and expensive bioassays to detect AT1R-AA. At present, the prevalence of AT1R-AA in large populations of preeclamptic women is unknown. In an attempt to clarify this issue, we assessed the presence and potential clinical significance of AT1R-AA in a large population of Mexican-Mestizo women with preeclampsia. METHODS: Using a cross-sectional design, we determined the presence of AT1R-AA in 525 pregnant women (99 healthy pregnant, 96 with mild preeclampsia, and 330 with severe preeclampsia) by a new bioassay that employs human embryonic kidney-293 cells stably expressing the recombinant rat AT1R and a 4x nuclear factor of activated T cells responsive luciferase construct as well as by the reference assay in Chinese hamster ovary (CHO) cells. RESULTS: We found that IgG obtained from sera of healthy pregnant women and patients with preeclampsia were unable to induce luciferase activity in both HEK-293 and Chinese hamster ovary cells expressing functional angiotensin II receptor type 1. Therefore, the frequency of patients with AT1R-AA was zero. CONCLUSION: We concluded that in Mexican-Mestizo women agonistic AT1R-AA cannot be invoked as a factor involved in the pathogenesis of preeclampsia. Whether these findings can be attributed to genetic or environmental factors remains unknown.