Antônio Carlos Vieira Cabral

Prognostic factors in fetal hydronephrosis : a multivariate analysis

Abstract With the increasing use of obstetric echography fetal hydronephrosis has been reported more frequently. The purpose of this study was to identify prognostic factors associated with adverse outcome, such as renal failure and death, in fetal hydronephrosis. One hundred and forty-eight children with fetal hydronephrosis were admitted, submitted to a systematic protocol, and prospectively followed. Prognostic factors associated with fetal echography and clinical and laboratory findings on admission were studied. The median follow-up was 39 months. The analysis was conducted in two steps. In a univariate analysis, variables associated with adverse outcome were identified by the Kaplan-Meier method. The variables that were significantly associated with adverse outcome were then included in a multivariate analysis. This analysis, using the multivariate Cox’s model, was performed to identify variables that were independently associated with a worse prognosis. Only variables that remained independently associated with adverse outcome were included in the final model. After final adjustment by Cox’s multivariate model, three variables were identified as independent predictors of adverse outcome: oligohydramnios, prematurity, and glomerular filtration rate lower than 20 ml/min. Thus, in the presence of oligohydramnios, prematurity, and abnormal renal function, the medical team must plan appropriate follow-up for infants at health centers prepared to investigate and treat uropathies in newborns.

Clinical course of 822 children with prenatally detected nephrouropathies.

BACKGROUND AND OBJECTIVES With the advent of fetal screening ultrasonography, the detection of congenital anomalies of the kidney and urinary tract (CAKUT) in utero has permitted early management of these conditions. This study aims to describe the clinical course of a large cohort of patients with prenatally detected nephrouropathies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this retrospective cohort study, 822 patients were prenatally diagnosed with CAKUT and systematically followed up at a tertiary Renal Unit for a median time of 43 months. Variables included in the analysis were sex, laterality, fetal ultrasonography (isolated versus associated hydronephrosis), and presence/absence of nephrouropathies. The events of interest were urinary tract infection, surgical interventions, hypertension, CKD, and death. Survival analyses were performed to evaluate time until occurrence of the events of interest. RESULTS Urinary tract infection occurred in 245 (29.8%) children, with higher risk in females (hazard ratio=1.30, 95% confidence interval=1.02-1.70, P=0.05); 22 patients (2.7%) had hypertension, and 49 (6%) patients developed CKD. The risk of CKD was greater in patients with associated hydronephrosis (hazard ratio=5.20, 95% confidence interval=2.90-9.30, P<0.001). Twelve patients (1.5%) died during follow-up. Death was significantly associated with being born during the first period of the study (hazard ratio=6.00, 95% confidence interval=1.60-22.50, P<0.001), associated hydronephrosis (hazard ratio=9.30, 95% confidence interval=2.90-29.30, P<0.001), and CKD (hazard ratio=170.00, 95% confidence interval=41.00-228.00, P<0.001). CONCLUSIONS In our series, the clinical course of prenatally detected CAKUT was heterogeneous, and those infants with associated hydronephrosis at baseline were identified as a high-risk subgroup.

Reduced plasma levels of angiotensin-(1-7) and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

The relationship between preeclampsia and the renin-angiotensin system (RAS) is poorly understood. Angiotensin I-converting enzyme (ACE) is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II) and inactivating the vasodilator angiotensin-(1-7) (Ang-(1-7)). ACE (I/D) polymorphism is characterized by the insertion (I) or deletion (D) of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D) polymorphism was correlated with plasma Ang-(1-7) levels and several RAS components in both preeclamptic (N = 20) and normotensive pregnant women (N = 20). The percentage of the ACE DD genotype (60%) in the preeclamptic group was higher than that for the control group (35%); however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260). The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005). Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012). A reduced plasma level of Ang-(1-7) was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146). In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

The pregnancy-induced increase of plasma angiotensin-(1-7) is blunted in gestational diabetes

BACKGROUND AND OBJECTIVE It has been shown that the circulating Renin-Angiotensin System (RAS) is activated during normal pregnancy, but little is known about RAS in pregnancies complicated by gestational diabetes (GDM). GDM is considered not merely a temporary condition, but a harbinger of hypertension and type 2 diabetes. The aim of this study was to evaluate the circulating RAS profile in normotensive women with GDM at the third trimester of pregnancy and to compare the results with healthy pregnant and non-pregnant age-matched women. METHODS The diagnostic criteria for GDM followed the recommendations of the American Diabetes Association. Angiotensin I (Ang I), Angiotensin II (Ang II) and Angiotensin 1-7 [Ang-(1-7)] were determined in 24 pregnant patients with GDM; 12 healthy pregnant women and 12 non-pregnant women by radioimmunoassay. RESULTS Levels of Ang I, Ang II and Ang-(1-7) were higher in pregnant women (p<0.05), but showed a different pattern in the GDM group, in which reduced Ang-(1-7) circulating levels were found (p<0.05). This observation was confirmed by the significantly lower Ang-(1-7)/Ang I ratio (p<0.05). CONCLUSION Our data suggest that reduced levels of the vasodilator Ang-(1-7) could be implicated in the endothelial dysfunction seen in gestational diabetic women during and after pregnancy.

Predictive Factors of Fetal Urethral Obstruction: A Multivariate Analysis

Objective: The purpose of this study was to identify predictive factors of fetal urethral obstruction. Methods: One hundred and forty-eight children with fetal hydronephrosis were admitted, submitted to a systematic protocol and prospectively followed. Possible predictive factors of urethral obstruction associated with fetal echography and clinical findings on admission were studied. The analysis was conducted in two steps. In a univariate analysis, variables associated with urethral obstruction were identified by the χ2 test or by Fisher’s exact test. Then, the variables that were significantly associated with urethral obstruction were included in a multiple logistic regression analysis. Results: After final adjustment by multiple logistic regression analysis, only two variables were identified as independent predictors of fetal urethral obstruction: oligohydramnios (odds ratio, OR = 5, 95% confidence interval, CI, = 1.3–15, p = 0.01) and megacystis (OR = 9, 95% CI = 2.0–40, p = 0.004). The sensitivity and specificity of the combination of both variables were 60 and 98.5%, respectively. Conclusions: The presence of oligohydramnios and megacystis on prenatal ultrasound is highly predictive of fetal urethral obstruction.

Dopplerfluxometria de artérias oftálmicas e avaliação da função endotelial nas formas precoce e tardia da pré-eclâmpsia

OBJETIVO: Avaliar possiveis diferencas entre a disfuncao endotelial, avaliada pela dilatacao fluxo-mediada, e hiperperfusao central, avaliada por dopplerfluxometria da arteria oftalmica, entre pacientes portadoras da forma precoce e tardia da pre-eclâmpsia. MATERIAIS E METODOS: O teste de dilatacao fluxo-mediada e a dopplerfluxometria da arteria oftalmica foram obtidos de 81 gestantes, sendo 56 portadoras de pre-eclâmpsia (26 na forma precoce e 30 na forma tardia) e 25 gestantes saudaveis (grupo controle). RESULTADOS: Portadoras de pre-eclâmpsia apresentaram valores menores de dilatacao fluxo-mediada quando comparadas ao grupo controle, tanto na forma precoce (7,62 ± 5,42% × 14,12 ± 6,14%; p = 0,02) como na forma tardia (5,83 ± 4,12% × 14,12 ± 6,14%; p = 0,00). Nao houve diferenca quando foram comparadas as duas formas (7,62 ± 5,42% × 5,83 ± 4,12%; p = 0,09). A dopplerfluxometria da arteria oftalmica apresentou-se significativamente menor nas pacientes portadoras de pre-eclâmpsia quando comparadas ao grupo controle, tanto na forma precoce (0,631 ± 0,024 × 0,737 ± 0,032; p = 0,01) como na forma tardia (0,653 ± 0,019 × 0,737 ± 0,032; p = 0,03). Nao houve diferenca entre as duas formas de apresentacao (0,631 ± 0,024 × 0,653 ± 0,019; p = 0,12). Os resultados basicamente demonstram reducao nos valores de dilatacao fluxo-mediada e dopplerfluxometria da arteria oftalmica nas formas tardia e precoce da pre-eclâmpsia quando comparadas ao grupo controle, sem, contudo, diferencas significativas entre as duas formas de apresentacao da doenca. CONCLUSAO: Os resultados indicam a presenca de disfuncao endotelial e hiperperfusao central em gestantes com pre-eclâmpsia, tanto na forma precoce como na tardia.

Comparação dos Métodos para Diagnóstico da Toxoplasmose Congênita

Objective: to test the effectiveness of the polymerase chain reaction (PCR) in the amniotic fluid for the detection of fetal contamination due to Toxoplasma gondii in pregnant women with acute infection and to correlate it with the inoculation technique and the histology of the placenta. Methods: thirty-seven patients were prospectively studied and the diagnosis was based on the identification of maternal acute infection followed by amniocentesis guided by ultrasound to obtain amniotic fluid for PCR and mice inoculation. The mothers were treated with spiramycin throughout pregnancy; when fetal infection was demonstrated, pyrimethamine and sulfadiazine were added to the regimen. The placentas were processed for histologic examination. The infants were followed for a period that varied from three to 23 months for the confirmation or exclusion of congenital toxoplasmosis. Results: association measures such as sensitivity, specificity and predictive values were calculated for PCR in the amniotic fluid, detection of the parasite through mice inoculation and placental histology and showed the following results: PCR values of sensitivity = 66.7% and specificity = 87.1%; the respective values for mice inoculation were 50 and 100% and for the placental histology were 80 and 66.7%. Conclusion: although PCR should not be used alone for the prenatal diagnosis of congenital toxoplasmosis, it is a promising method and deserves more studies to improve its efficacy.

Endothelial function, uterine perfusion and central Flow in pregnancies complicated by Preeclampsia

BACKGROUND The physiopathology of Preeclampsia (PE) is characterized by a deficiency in the process of placentation, systemic endothelial dysfunction and Central Nervous System (CNS) hyperflow. From a clinical point of view, it would be interesting to determine the occurrence of these phenomena before the onset of clinical manifestations of the disease, raising the possibility of new methods for predicting PE. OBJECTIVE Compare the process of placentation, endothelial function and CNS hyperflow in pregnant women at high risk for the development of PE who subsequently developed or not the syndrome. METHODS A total of 74 pregnant women underwent the Flow-Mediated Dilation (FMD) of the brachial artery, Doppler study of uterine and ophthalmic arteries for the assessment of endothelial function, process of placentation and central hyperflow, respectively. The examinations were performed between 24 and 28 weeks of gestation and were followed until the postpartum period for data collection. RESULTS Fifteen patients had PE and 59 remained normotensive until the puerperium. Patients who subsequently developed PE had between 24 and 28 weeks of gestation, higher pulsatility index of uterine arteries and lower values of FMD (p < 0.001 and p = 0.001, respectively). However, there was no difference in the values obtained in the resistive index in the ophthalmic artery (p = 0.08). CONCLUSION The data obtained suggest that the deficiency in the process of placentation and endothelial dysfunction chronologically precede the clinical manifestations of PE, which does not occur with CNS hyperflow.

Antenatal Ultrasonographic Anteroposterior Renal Pelvis Diameter Measurement: Is It a Reliable Way of Defining Fetal Hydronephrosis?

Purpose. It was to quantify the intraobserver and interobserver variability of the sonographic measurements of renal pelvis and classify hydronephrosis severity. Methods. Two ultrasonographers evaluated 17 fetuses from 23 to 39 weeks of gestation. Renal pelvis APD were taken in 50 renal units. For intraobserver error, one of them performed three sequential measurements. The mean and standard deviation from the absolute and percentage differences between measurements were calculated. Bland-Altman plots were used to visually assess the relationship between the precision of repeated measurements. Hydronephrosis was classified as mild (5.0 to 9.9 mm), moderate (10.0 to 14.9 mm), or severe (≥15.0 mm). Interrater agreement were obtained using the Kappa index. Results. Absolute intraobserver variation in APD measurements was 5.2 ± 3.5%. Interobserver variation of ultrasonographers was 9.3 ± 9.7%. Neither intraobserver or interobserver error increased with increasing APD size. The overall percentage of agreement with the antenatal hydronephrosis diagnosis was 64%. Cohens Kappa to hydronephrosis severity was 0.51 (95% CI, 0.33 to 0.69). Conclusion. Inter and intraobserver APD measurement errors were low in these group, but the agreement to hydronephrosis diagnosis and classification was fair. We suggest that standard and serial APD measurement can better define and evaluate fetal hydronephrosis.

Presymptomatic prediction of preeclampsia with angiogenic factors, in high risk pregnant women

Introduction: The aim of this study was to investigate the value of placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PLGF ratio, in predicting symptomatic preeclampsia (PE). Methods: A prospective longitudinal study was carried out on 71 high risk preeclamptic women cohort. All of them had normal blood pressure level (≤140/90 mmHg) at the time of enrolment, 26.8 ± 1.5 weeks. Maternal blood was collected and plasma was stored in a freezer at −80 °C. PE was defined according to the National High Blood Pressure Education Program Working Group Criteria. Accuracy of angiogenic factors in predicting PE was evaluated using Receiver-operating characteristics. Results: Maternal plasma concentrations of PLGF and sFlt-1 were able to predict PE (0.90, p < 001; 0.78, p = 0.003, area under the curve, respectively) but the sFlt-1/PLGF ratio presented the best prediction potential over the others (0.95, area under the curve, p < 0.001). Conclusion: All angiogenesis factors were effective biomarkers in predicting PE during the second trimester, before the clinical onset of PE.