Long term follow up of biomarkers of podocyte damage and renal function in patients with and without preeclampsia / Seguimento de longo prazo com biomarcadores de dano podocitário e função renal em pacientes com e sem pré-eclâmpsia

ABSTRACT Introduction: preeclampsia can be associated with future renal disease. Objectives: To measure changes in renal function overtime in patients with preeclampsia. Methods: urine and serum samples from eleven patients with preeclampsia and eight patients with a normal pregnancy were obtained during pregnancy, postpartum, and 3 years after delivery. Urine podocalyxin, protein, and serum creatinine were measured. Results: after 3 years, there were no significant differences in urinary podocalyxin in patients with or without preeclampsia: 4.34 ng/mg [2.69, 8.99] vs. 7.66 ng/mg [2.35, 13], p = 0.77. The same applied to urinary protein excretion: 81.5 mg/g [60.6, 105.5] vs. 43.2 mg/g [20.9, 139.3] p = 0.23. Serum creatinine was 0.86 mg/dL [0.7, 0.9] vs. 0.8 mg/dL [0.68, 1] p = 0.74 in those with and without preeclampsia. In normal patients, urinary podocalyxin decreased from 54.4 ng/mg [34.2, 76.9] during pregnancy to 7.66 ng/mg [2.35, 13] three years after pregnancy, p = 0.01. Proteinuria decreased from 123.5 mg/g [65.9, 194.8] to 43.2 mg/g [20.9, 139.3], p = 0.12. In preeclampsia patients, urinary podocalyxin decreased from 97.5 ng/mg [64.9, 318.4] during pregnancy to 37.1 ng/mg within one week post-partum [21.3, 100.4] p = 0.05 and 4.34 ng/mg [2.69, 8.99] three years after, p = 0.003. Proteinuria was 757.2 mg/g [268.4, 5031.7] during pregnancy vs. 757.2 mg/g [288.2, 2917] postpartum, p = 0.09 vs. 81.5 mg/g [60.6, 105.5] three years later, p = 0.01. Two patients still had proteinuria after 3 years. Conclusions: in preeclampsia patients, postpartum urinary podocalyxin decreased before proteinuria. After three years, serum creatinine, urinary podocalyxin, and protein tended to normalize, although some patients still had proteinuria.

RESUMO Introdução: a pré-eclâmpsia pode estar associada à doença renal no futuro. Objetivos: medir mudanças na função renal ao longo do tempo em pacientes com pré-eclâmpsia. Métodos: amostras de urina e soro de onze pacientes com pré-eclâmpsia e oito pacientes com gravidez normal foram obtidas durante a gravidez, pós-parto e 3 anos após o parto. Medimos podocalixina na urina, proteína e creatinina sérica. Resultados: após 3 anos, não houve diferenças significativas na podocalixina urinária em pacientes com ou sem pré-eclâmpsia: 4,34 ng/mg [2,69, 8,99] versus 7,66 ng/mg [2,35, 13], p = 0,77. O mesmo se aplicou à excreção urinária de proteínas: 81,5 mg/g [60,6, 105,5] vs. 43,2 mg/g [20,9, 139,3] p = 0,23. A creatinina sérica foi de 0,86 mg/dL [0,7, 0,9] vs. 0,8 mg/dL [0,68, 1] p = 0,74 naqueles com e sem pré-eclâmpsia. Em pacientes normais, a podocalixina urinária diminuiu de 54,4 ng/mg [34,2, 76,9] durante a gestação para 7,66 ng/mg [2,35, 13] três anos após a gravidez, p = 0,01. A proteinúria diminuiu de 123,5 mg/g [65,9, 194,8] para 43,2 mg/g [20,9, 139,3], p = 0,12. Em pacientes com pré-eclâmpsia, a podocalixina urinária diminuiu de 97,5 ng/mg [64,9, 318,4] durante a gravidez para 37,1 ng/mg em uma semana de pós-parto [21,3, 100,4] p = 0,05 e 4,34 ng/mg [2,69, 8,99] três anos depois, p = 0,003. A proteinúria foi de 757,2 mg/g [268.4, 5031.7] durante a gravidez vs. 757,2 mg/g [288.2, 2917] pós-parto, p = 0.09 vs. 81.5 mg/g [60.6, 105.5] três anos depois, p = 0.01. Dois pacientes ainda apresentavam proteinúria após 3 anos. Conclusões: em pacientes com pré-eclâmpsia, a podocalixina urinária pós-parto diminuiu antes da proteinúria. Após três anos, a creatinina sérica, a podocalixina urinária e a proteína tenderam a se normalizar, embora alguns pacientes ainda tivessem proteinúria.

Natriuria and calciuria levels in preeclampsia: a cross-sectional study / Valores de natriúria e calciúria na pré-eclâmpsia: estudo transversal

CONTEXT AND OBJECTIVE Sodium excretion abnormalities in preeclampsia have been studied in relation to several factors. The objective of this study was to compare natriuria (mEq/24 h) and calciuria levels (mg/24 h) in preeclamptic patients. DESIGN AND SETTING An analytical cross-sectional study with a control group was conducted in the obstetric center and the high-risk pregnancy outpatient clinic at a university hospital in southern Brazil, and in a primary healthcare unit in the same city, including pregnant women with mild preeclampsia, severe preeclampsia or chronic hypertension, and women with normal pregnancies (14 patients in each group). METHOD Natriuria was measured using an ion-selective electrode in an automated clinical chemistry analyzer (Hitache 917, Roche). All the patients collected 24-hour urine, at home or at the hospital, for analysis of proteins, creatinine, calcium, sodium and uric acid. Quantitative variables with asymmetrical distribution were described using the median, minimum and maximum, and were compared using the Kruskal-Wallis test. The results were logarithmically transformed, with one-way analysis of variance (ANOVA) by ranks and then the post-hoc Tukey test, and were analyzed by means of the Spearman correlation and receiver operating characteristic (ROC) curve. The significance level used was 0.05. RESULTS There were significant differences between the groups in comparing severe preeclampsia with chronic hypertension and severe preeclampsia with controls (P < 0.0001 for both measurements). CONCLUSION Natriuria levels may be lower in preeclampsia when associated with calciuria. Natriuria assessment is an additional test for differential diagnosis of hypertensive diseases in pregnancy, but is a poor predictor when used alone. .

CONTEXTO E OBJETIVO Alterações na excreção de sódio têm sido estudadas na pré-eclâmpsia relacionadas a vários fatores. O objetivo deste estudo foi comparar natriúria (mEq/24 h) com os níveis de calciúria (mg/24 h) em pacientes pré-eclâmpticas. ESTUDO E LOCAL Estudo transversal analítico com grupo controle foi realizado no Centro Obstétrico e no Ambulatório de Gestação de Alto Risco em um hospital universitário no sul do Brasil, e na Unidade Básica de Saúde na mesma cidade, incluindo gestantes com pré-eclâmpsia leve e grave, hipertensão crônica e gestações normais, com 14 pacientes em cada grupo. MÉTODO A natriuria foi dosada através da medida de íon eletrodo seletivo, utilizando analizadores automáticos de química clínica (Hitache 917 Roche). Todas as pacientes coletaram urina de 24 h, em casa ou no hospital, para análise de proteínas, creatinina, cálcio, ácido úrico e sódio. As variáveis quantitativas com distribuição assimétrica foram descritas por mediana, mínimo e máximo, e comparadas por teste Kruskal-Wallis. Os resultados foram transformados logaritmicamente, com ANOVA one-way por ranking e, posteriormente, teste post-hoc de Tukey, e foram analisados por médias de correlações de Spearman e curva ROC (receiver operating characteristic). O nível de significância adotado foi de 0.05. RESULTADOS Foram encontradas diferenças significativas entre os grupos quando comparados pré-eclâmpsia grave com hipertensão crônica e pré-eclâmpsia grave com controles (P < 0.0001 para ambas as medidas). CONCLUSÃO Natriúria pode estar reduzida na pré-eclâmpsia ...

Valor del examen de orina simple para el diagnóstico de preeclampsia / Value of simple urine test for the diagnosis of preeclampsia

Objetivos: Determinar el valor del examen de orina simple en pacientes embarazadas de 30 a 41 semanas de gestación para diagnosticar preeclampsia, comparándolo con la orina de 24 horas. Metodología: Estudio analítico realizado con los resultados de laboratorio de orina simple y orina de 24 horas de pacientes embarazadas con hipertensión inducida por el embarazo, revisando un total de 235 expedientes clínicos...

[Comparing the protein of 2-hour and 24-hour urine samples in patients with suspected preeclampsia]

Determining the protein content of a 24-hour urine sample is the gold standard for diagnosis of hypertensive disorders in pregnancy. To determine whether the 2-hour urine protein value can be used as a substitute for the 24-hour urine protein value in patients with preeclampsia. This was a cross sectional study performed on 60 inpatient women with suspected preeclampsia due to positive urinary test strip with minimum protein content of 1[+] and BP >/= 140/90 at Kosar Teaching Hospital in Qazvin [Iran] during autumn and winter 2008. Urine samples were collected within 24 hours in successive periods: The first 2-hour and the next 22-hours urine, in separate containers. The protein contents of 2-hour and 24-hour urine samples were calculated and the correlation between both groups was determined using Pearson's correlation. The cut off point for 2-hour urine protein was obtained with ROC curve. Of 60 patients studied, 42 had proteinuria less then 0.3gr/24h and 18 with proteinuria higher than 0.3gr/24h. No patient with severe proteinuria [2gr>24h] was detected. There was a significant correlation between the 2-hour and 24-hour urine protein content in patients' samples. Pearson's correlation coefficient [r] was 0.788 [p=0.000]. The cut off point for mild proteinuria was determined at 0.035gr/2h with sensitivity, specificity, positive predictive value, and negative predictive value of 63.3%, 89.5%, 77.8% and 80.95%, respectively. Total protein values of 2-hour samples positively correlated with values of 24-hour samples of preeclampsia women and therefore can be substituted for assessing the protein content of 24-hour urine samples as a more convenient, faster, and cheaper method for diagnosis of preeclampsia

use of protein to creatinin ratio in random urine sample for prediction of proteinuria in preeclampsia

Preeclampsia occurs in approximately 17% of pregnancies, unknown etiology. The gold standard method for assessment of protein excreted in the urine to diagnose preeclampsia is a 24- h urine collection. However, this method is cumbersome and time consuming for the patient and laboratory. The aim of this study is to evaluate the use of protein to creatinin ratio in random urine sample for prediction of proteinuria in preeclampsia. This study is a cross-sectional descriptive study. This study was performed on 150 pregnant women who were hospitalized as preeclampsia in Ghaem Hospital during early 2006. At first, a random urine sample was collected for each patient to determine protein/creatinine ratio. Then, 24-h urine collection was analyzed for the measurement of proteinuria. Statistical analysis was performed with SPSS software and Pearson correlation coefficient for evaluation of the results. A total of 150 patients were entered the study. There was a significant relation between the 24-h urine protein and protein to creatinine ratio [r=0.659, P<0.001]. The use of e protein-to-creatinin ratio in random urine sample is a suitable replacement for the measurement of 24-h urine protein. This method is quick, reliable and cost effectiveness

comparison of spot urine protein-creatinine ratio with 24-hour urine protein excretion in women with preeclampsia

Proteinuria is an important diagnostic component of preeclampsia. We prospectively compared the results of spot urine protein-creatinine [P/C] ratio with 24-hour urine protein excretion in women with preeclampsia. A total of 81 pregnant women with preeclampsia were prospectively studied for proteinuria. Urine P/C ratio was determined in a spot mid-stream urine sample, and the amount of protein excretion was measured in 24-hour urine collected on the subsequent day. The correlation between the spot P/C ratio and 24-hour urine protein excretion was assessed. Diagnostic value of P/C ratio was expressed in terms of specificity and sensitivity. The receiver operating characteristic curve analysis was used to determine the best discriminator values of the spot urine P/C ratios for preeclampsia [proteinuria >/= 300 mg/24 h]. There was a strong correlation between the spot P/C ratio and 24-hour urine protein excretion [r = 0.84; P < .001]. The optimal spot P/C ratio cutoff point was 0.20 for 300 mg/24 h of protein excretion [preeclampsia], with a sensitivity, specificity, positive predictive value, and negative predictive value of 91.2%, 87.8%, 94.4%, and 96.8%, respectively. The spot P/C ratios less than 0.19 yielded a sensitivity of 100% for exclusion of preeclampsia. We found that there is a significant correlation between the spot urine P/C ratio and 24-hour urine protein excretion in women with preeclampsia. Urine P/C ratio could be used for exclusion of preeclampsia

Correlation of 4- and 24-hour urine protein in women with initially diagnosed hypertensive disorders in pregnancy.

OBJECTIVE: To determine whether 4-hour urine protein value correlates with 24-hour urine protein value in women with hypertensive disorders in pregnancy. STUDY DESIGN: Cross-sectional study was performed in 38 in-patient pregnant women who were initially diagnosed as having hypertensive disorders in pregnancy. Urine samples were collected within 24 hours in 2 successive periods: the first 4-hour and the next 20-hour urine, in separate containers. The urine volume, urine protein and creatinine concentrations were thus separately measured. The 4- and 24-hour urine proteins were calculated and the correlation between both groups was determined by simple linear regression analysis. RESULTS: A total of 38 patients were recruited into the study, 26 had mild preeclampsia, 5 had severe preeclampsia, and 7 had superimposed preeclampsia. The result of the 4-hour urine protein was found to correlate with those of the 24-hour urine protein for patients with hypertensive disorders in pregnancy (p < 0.001). CONCLUSION: Total protein values of 4-hour samples positively correlated with values of 24-hour samples of patients with hypertensive disorders in pregnancy. This might be modified and used for urine protein collection in outpatients to improve the compliance.

Avaliaçäo da sensibilidade e especificidade do dipstick como teste de rastreamento para doença hipertensiva induzida pela gestaçäo / Assessment of dipstick sensitivity and specificity for screening of hypertensive pregnancies

Os distúrbios hipertensivos da gestação são importante fator causal de morbimortalidade materna, fetal e neonatal. É inquestionável a necessidade de um diagnóstico preciso e simplificado para uso da emergência obstétrica. A fita reagente de imersão em urina (dipstick) é utilizada amplamente como método de detecção de proteína na urina. Este estudo tem como objetivo principal comparar os resultados do dipstick em amostra urinária ao resultado da proteinúria de 24 horas, considerado teste padrão-ouro na detecção de proteínas na urina...

Índice proteinúria/creatininúria em gestantes com hipertensäo arterial / The protein/creatinine ratio in hypertensive pregnant women

Para estabelecer o nível da relação proteína/creatinina urinária com melhor predição para o diagnóstico de proteinúria significativa em gestantes com hipertensão arterial sistêmica, foi feita revisão da literatura comparando coeficientes de correlação entre a proteinúria de 24 horas e o índice proteína/creatinina urinária...

Calciuria and preeclampsia

Urinary calcium excretion has been reported to be diminished in preeclampsia. The objective of the present study was to determine urinary calcium excretion in pregnant patients with chronic arterial hypertension (CAH) and preeclampsia (PE), and in normotensive patients (N). Forty-four pregnant patients (gestational age, 20-42 weeks; 18 CAH, 17PE, 9N) were evaluated for calciuria, proteinuria, plasma uric acid and blood pressure. Patients with PE (82 + 15.1 mg/24 h) showed significantly lower calciuria (P<0.05) than the group with CAH (147 + 24.9 mg/24 h) and the N group (317 + 86.0 mg/24 h) (P<0.05, Student t-test), Plasma uric acid was significantly higher in the PE group (6.1 + 0.38 mg/dl) than the CAH group (5.0 + 0.33 mg/dl; P<0.05), which also presented higher proteinuria levels, although the difference was not statistically significant. Diastolic and systolic blood pressure did not differ between the PE (164 + 105 mmHg) and CAH (164 + 107 mmHg) groups. Calciuria was significantly lower in the group with preeclampsia than in the group with chronic arterial hypertension. We conclude that calciuria can be a further factor for identifying preeclampsia.

Lower circulating insulin-like growth factor I and 1,25-dihydroxyvitamin D levels in preeclampsia

Objetivo. Evaluar si las concentraciones e la somatomedina C )IGF-I) en el suero de mujeres preeclámticas son menores que las encontradas en mujeres embarazadas normotensasm y si las concentraciones en el suero del IGF-I se correlacionan con las de la 1,25-dihidroxivitamina D (1,25-(OH)2D). Diseño del estudio. El estudio fue transversal y se realizó entre las semanas 26.7 y 39.7 del embarazo. Los resultados obtenidos en mujeres preeclámpticas se compararon con los obtenidos en mujeres embarazadas normotensas de la misma edad gestacional (grupo testigo). Lugar. Todas las voluntarias eran pacientes del Hospital General de México, México, D.F., y todos los análisis de laboratorio se realizaron en el Instituto Nacional de la Nutrición Salvador Zubirán, México, D.F. Sujetos. En el estudio participaron 26 mujeres preeclámpticas y 26 mujeres embarazadas normotensas. Todas participaron informada y libremente. Procedimiento. Se realizaron las siguientes medicaciones: concentraciones en el suero del IGF-I, de la 1,25-(OH)2D, de la hormona paratiroidea intacta (PTH), del fósforo inorgánico, de la creatinina y del calcio y magnesio totales y iónicos. Además, se midieron la excreción urinaria del calcio y la depuración renal de la creatinina y se obtuvieron datos antropométricos y sobre la dieta habitual. Todos los análisis de laboratorio se realizaron en forma ciega. La comparación entre grupos se realizó mediante la prueba U de Mann-Whitney y las asociaciones entre variables se analizaron mediante las pruebas de correlación de rangos de Sperman y regresión por pasos. Resultados. Las concentraciones del IGF-I en el suero fueron 26.1 ñ 10.2 nmol/L (promedio ñ DE) en el grupo de mujeres preeclámticas y 49.9 ñ 14.3 nmol/L en el grupo testigo (p= 0.0003). Las concentraciones de la 1,25-(OH)2d en el suero fueron 43.6 ñ 8.2 pg/mL en el grupo de mujeres preeclámpticas y 52.1 ñ 10.2 pg/mL en el grupo testigo (p= 0.005). Las concentraciones de PTH intacta en el suero fueron similares en el grupo de mujeres preeclámpticas y en el grupo testigo. Las concentraciones en el suero del IGF-I, de la 1,25-(OH)2D y de la PTH intacta se correlacionaron significativamente entre sí en el grupo testigo. En las mujeres preeclámpticas sólo se correlacionaron los valores del IGF-I y de la 1,25-(OH)2D. Conclusiones. Del presente estudio se derivan dos observaciones originales: primero, que las concentraciones del IGF-I en el suero de las mujeres preeclámpticas fueron significativamente menores que las observadas en las embarazadas testigo; y segundo, la existencia de una correlación significativa entre las concentraciones séricas de IGF-I y de 1,25-(OH)2D tanto en el grupo testigo como en las mujeres preclámpticas

Perfil elecroforético de la proteinuria en el embarazo normal y en la hipertensión gestacional / Electroforetic profile of proteinuria in normal pregnancy and in gestational hypertension

El objeto de este trabajo fue la determinación del perfil electroforético y la evaluación del tipo de la proteinuria en el embarazo normal y en mujeres con hipertención gestacional acompañada o no de proteinuria patológica, utilizando para el efecto electroforesis de alta resolución en geles de SDS-poliacrilamida. El estudio se realizó con pacientes del Hospital General de la Secretaría de Salud en Durango, México. Se formaron tres grupos; uno (n= 13) formado por mujeres con embarazo normal; el segundo, paciente con hipertensión gestacional sin proteinuria patológica (n= 25) y el tercero, pacientes con hipertensión gestacional y proteinuria patológica (n= 12). El perfil electroforético en los tres grupos mostró proteínas de alto y bajo peso molecular, correspondiendo por lo tanto en los tres casos a proteinuria mixta (glomerular y tubular). En las muestras del grupo de hipertensión gestacional con proteinuria patológica se observó mayor contenido de IgG y transferrina. Se concluye que la proteinuria fisiológica del embarazo normal y la proteinuria patológica en la hipertención gestacional difieren cuantitativamente de modo absoluto y relativo. El método analítico utilizando en este estudio es útil en la evaluación de compromiso renal en padecimientos que cursan con proteinuria

Preeclampsia: excresión de calcio / Preeclampsia: excretion of calcium

El objetivo del trabajo fue determinar los valores de calcio urinario en preeclampsia y compararlo con embarazadas normales. Se realizó la recolección de orina en 24 horas de 60 pacientes en el tercer trimestre de gestación: 30 con preeclampsia y 30 normotensas. El ácido úrico sérico fué significativamente más bajo en las normotensas (3,49 =/-, 1,21 mg/dl) que en las preeclampticas (6,26 +/- 1,58 mg/dl) p 0,0001), al igual que la proteinuria en 24 horas (89 +/- 79,43 mg en las normotensas vs. 443 +/- 543, 30 mg en las preeclampticas) (p 0,00001). La excreción de calcio urinario fué más bajo en el grupo con preeclampsia (39,78 +/- 25,32 mg/24h) que en las normotensas (133,8 +/- 85,12 mg/24h) (p 0,00001). El calcio sérico no presentó diferencias significativas, encontrándose los valores en el rango de normalidad. Es necesario realizar otros estudios a gran escala para establecer conclusiones definitivas en la excreción del calcio urinario y que este pueda ser utilizado como prueba evaluadora.

Urinary Estriol Determinations in Normal and Pathological Pregnancies

Estriol excreation was studied in 216 normal and 61 pathologic pregnancies. The 95% fiducial limits of the normal excretion of estriol, within which 95% out of 100 future determinations in normal pregnancies are expected to fall, were established. The estriol curve in normal pregnancy in this study agrees well in its general shape with those presented by previous investigators who used different chemical methods of determination. The estriol values in pathologic pregnancies with preeclampsia. intrauterine fetal death and antepartum hemorrage have been analyzed. The clinical significance of estriol determinations during pregnancy was discussed.