Protein-creatinine ratio and albumin-creatinine ratio for the diagnosis of significant proteinuria in pregnant women with hypertension: Systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: The gold standard for assessment and diagnosis of significant proteinuria in pregnancy has been by 24-hour urine collection and analysis. Determining fast, accurate methods to identify clinically significant proteinuria would aid diagnosis of pre-eclampsia. The objective of this study was to determine the accuracy of spot protein-creatinine ratio (PCR) and albumin-creatinine ratio (ACR) measurements compared with 24-hour urine collection for the identification of clinically significant proteinuria in women with hypertensive disorders of pregnancy. METHODS: Search strategies were developed for electronic databases from inception to 1st October 2020. Data were assessed for methodological quality using the QUADAS-II checklist for risk of bias and quality of the evidence using GRADE. Meta-analysis was performed where there were at least four studies presenting data for the same comparison (test and threshold). This is an update of the review for NICE guideline NG133 (published June 2019) and includes additional data. RESULTS: Twenty-nine studies were included. PCR measurements (28 studies) showed high sensitivity (91%) and specificity (89%) at a threshold of 30 mg/mmol (n = 3577). Higher thresholds (>60 mg/mmol) increased specificity, but reduced sensitivity. At a threshold of PCR 30 mg/mmol, diagnostic accuracy improved for sensitivity and specificity (93% for both) in studies where the first morning void was excluded (n = 1868). Data available (4 studies) for ACR supports ruling out of significant proteinuria at less than 2 mg/mmol, though evidence was limited by paucity of data and wide confidence intervals around the result. CONCLUSIONS: PCR and ACR have high accuracy compared to the gold standard 24-hour urine collection.

Urinary abnormalities and renal function in pregnant women with chronic hypertension. / Avaliação de alterações urinárias e função renal em gestantes com hipertensão arterial crônica.

INTRODUCTION: Renal involvement in pregnant women with chronic hypertension is not widely known. OBJECTIVES: 1- To describe the epidemiological profile of pregnant women with chronic hypertension; 2- To evaluate urinary abnormalities (by urinalysis), renal function (serum creatinine and cystatin C, and estimated glomerular filtration rate (eGFR); 3- To evaluate the pregnancy outcome in chronic hypertension. METHODS: 103 pregnant women with chronic hypertension (blood pressure over 140/90 mmHg, detected previously to pregnancy or until the 20th week) were submitted to clinical and laboratorial evaluation. RESULTS: Pregnant women were 21-45 (mean: 34) years-old. Protein/creatinine ratio in random urine was elevated in 5.2% (0.0-6.4g/g), serum creatinine in 19.6% and cystatin C in 14.7% of them. It was observed that characteristics of pregnant patients and their newborns (vs. frequencies of the cases with CKD-EPI cystatin C < 60 ml/min/1.73 m2) were: 20.5% (33.3%) of preterm birth < 37 weeks, 17.5% (22.2%) of birth weight < 2500g and 17.5% (22.2%) of small for gestational age; superimposed preeclampsia-eclampsia occurred in 24.7% (22.2%) of the cases. CONCLUSIONS: Renal abnormalities were detected by proteinuria, determinations of serum creatinine and cystatin C in 5.2, 19.6 and 14.7% of the cases. The results suggest that the formulas CKD-EPI and MDRD can have applicability in assessing renal function in pregnant women. It was also shown a high frequency of preterm birth or with < 2500g at birth or small for gestational age, as well as of superimposed preeclampsia-eclampsia (24.7%) in pregnant women with chronic hypertension.

Avaliação de alterações urinárias e função renal em gestantes com hipertensão arterial crônica / Urinary abnormalities and renal function in pregnant women with chronic hypertension

Resumo Introdução: O acometimento renal em gestantes portadoras de hipertensão arterial crônica (HAC) não é amplamente conhecido. Objetivos: 1- Descrever o perfil epidemiológico de pacientes com HAC; 2- Avaliar a ocorrência de alterações urinárias e de função renal (por meio de determinação sérica de creatinina, cistatina C e ritmo de filtração glomerular estimada - RFGe); 3- Avaliar o desfecho das gestações em HAC. Métodos: Foram submetidas a avaliações clínicas e laboratoriais 103 gestantes com HAC (pressão arterial acima de 140/90 mmHg, identificada previamente à gestação ou até a 20ª semana). Resultados: As gestantes tinham 21-45 (média: 34) anos; 12,6% eram primigestas, 64,1% tiveram múltiplas gestações. A relação proteinúria/creatininúria em amostra isolada estava alterada em 5,2% casos (0-6,44 g/g), creatinina sérica estava elevada em 19,6% e cistatina C em 14,7%. Na avaliação das características da gestação em pacientes com HAC e seus recém-nascidos (RN) (vs. frequências nos casos com CKD-EPI cistatina C < 60 ml/min/1,73 m2), observou-se: 20,5% (33,3%) de nascidos pré-termo < 37 sem, 17,5% (22,2%) de RN com peso < 2500 g e 17,5% (22,2%) de RN pequeno para a idade gestacional (PIG); sobreposição de DHEG ocorreu em 24,7% (22,2%) dos casos. Conclusão: Alterações renais foram identificadas por proteinúria, creatinina e cistatina C séricas em 5,2%, 19,6 e 14,7% das gestantes. Os resultados sugerem que as fórmulas do CKD-EPI e MDRD também podem ter aplicabilidade nessa avaliação em gestantes. Detectou-se alta frequência de RN pré-termo ou com menos de 2500 g ao nascer ou PIG, assim como de sobreposição de DHEG (24,7%) em gestantes com HAC.

Abstract Introduction: Renal involvement in pregnant women with chronic hypertension is not widely known. Objectives: 1- To describe the epidemiological profile of pregnant women with chronic hypertension; 2- To evaluate urinary abnormalities (by urinalysis), renal function (serum creatinine and cystatin C, and estimated glomerular filtration rate (eGFR); 3- To evaluate the pregnancy outcome in chronic hypertension. Methods: 103 pregnant women with chronic hypertension (blood pressure over 140/90 mmHg, detected previously to pregnancy or until the 20th week) were submitted to clinical and laboratorial evaluation. Results: Pregnant women were 21-45 (mean: 34) years-old. Protein/creatinine ratio in random urine was elevated in 5.2% (0.0-6.4g/g), serum creatinine in 19.6% and cystatin C in 14.7% of them. It was observed that characteristics of pregnant patients and their newborns (vs. frequencies of the cases with CKD-EPI cystatin C < 60 ml/min/1.73 m2) were: 20.5% (33.3%) of preterm birth < 37 weeks, 17.5% (22.2%) of birth weight < 2500g and 17.5% (22.2%) of small for gestational age; superimposed preeclampsia-eclampsia occurred in 24.7% (22.2%) of the cases. Conclusions: Renal abnormalities were detected by proteinuria, determinations of serum creatinine and cystatin C in 5.2, 19.6 and 14.7% of the cases. The results suggest that the formulas CKD-EPI and MDRD can have applicability in assessing renal function in pregnant women. It was also shown a high frequency of preterm birth or with < 2500g at birth or small for gestational age, as well as of superimposed preeclampsia-eclampsia (24.7%) in pregnant women with chronic hypertension.

[Podocyturia in pregnant women with chronic hypertension may predict kidney injury?]. / Podocitúria em gestantes hipertensas crônicas pode predizer dano renal?

PURPOSE: To evaluate the presence of podocyturia in chronic hypertensive pregnant women in the third trimester of pregnancy and its possible association with renal disease. METHODS: This was an observational study of a convenience sample of 38 chronic hypertensive pregnant women. The podocytes were labeled by the indirect immunofluorescence technique with anti-podocin and diamidino-phenylindole (DAPI). The count was made on 30 random fields analyzed and corrected according to urinary creatinine (podocytes/mg creatinine). The patients were assigned to two groups: NG (normal glomerular function), up to 100 podocytes, and GP (probable glomerulopathy), more than 100 podocytes. Urinary creatinine was measured by the alkaline picrate method. The variables analyzed were body mass index, gestational age, and systolic and diastolic blood pressure at the time of sample collection. Data were analyzed using the SPSS - version 16.0 (IBM - USA). Statistical analysis was performed by the χ2 test, and significant differences were considered when p<0.05. RESULTS: The median podocyte count was 20.3 (0.0-98.1) for group GN, and 176.9 (109.1-490.6) for GP. The mean body mass index was 30.2 kg/m2 (SD=5.6), mean gestational age was 35.1 weeks (SD=2.5), median systolic blood pressure was 130.0 mmHg (100.0-160.0) and median diastolic blood pressure was 80.0 mmHg (60.0-110.0). There was no significant correlation between podocyturia and body mass index (p=0.305), gestational age (p=0.392), systolic blood pressure (p=0.540) or diastolic blood pressure (p=0.540). CONCLUSIONS: In this study, there was no podocyturia pattern consistent with the presence of active renal disease, although some of the women studied (15.8%) exhibited a significant loss. We believe that it is premature to recommend the inclusion of the determination of podocyturia in routine prenatal clinical practice in chronically hypertensive pregnant women.

Podocitúria em gestantes hipertensas crônicas pode predizer dano renal? / Podocyturia in pregnant women with chronic hypertension may predict kidney injury?

OBJETIVO: Avaliar a presença de podocitúria em gestantes hipertensas crônicas no terceiro trimestre da gestação e a associação com doença renal. MÉTODOS: Estudo observacional descritivo em uma amostra de conveniência de 38 gestantes hipertensas crônicas. Os podócitos foram marcados com técnica de imunofluorescência indireta com antipodocina e diamidino-fenilindol (DAPI). A contagem foi feita a partir de 30 campos analisados de forma aleatória, corrigida pela creatinina urinária (podócitos/mg de creatinina). Foram assumidos dois grupos: grupo GN (função glomerular normal), com até 100 podócitos, e grupo GP (provável glomerulopatia), com mais de 100 podócitos. A dosagem de creatinina foi realizada com uso da técnica do picrato alcalino. As variáveis de análise foram o índice de massa corpórea, a idade gestacional na coleta, a pressão arterial sistólica e a pressão arterial diastólica no momento da coleta. Para a análise dos dados, foi utilizado o programa SPSS - versão 16.0. (IBM - USA). Nas análises estatísticas, foi utilizado o teste do χ2, sendo consideradas diferenças significantes valores de p<0,05. RESULTADOS: A contagem de podócitos no grupo GN teve mediana de 20,3 (0,0 a 98,1), e no grupo GP, de 176,9 (109,1 a 490,6). A média do índice de massa corpórea foi 30,2 kg/m2 (DP=5,6), a média da idade gestacional foi de 35,1 semanas (DP=2,5), a mediana da pressão arterial sistólica foi de 130,0 mmHg (100,0-160,0) e a mediana da pressão arterial diastólica de 80,0 mmHg (60,0-110,0). Não houve correlação significativa entre podocitúria e índice de massa corpórea (p=0,305), idade gestacional na coleta (p=0,392), pressão arterial sistólica (p=0,540) e pressão arterial diastólica (p=0,540). CONCLUSÕES: Não foi identificado um padrão de podocitúria compatível com a presença de glomerulopatia ativa, ainda que algumas das gestantes (15,8%) tenham exibido perda podocitária expressiva. Consideramos ser prematuro recomendar para a prática ...

PURPOSE: To evaluate the presence of podocyturia in chronic hypertensive pregnant women in the third trimester of pregnancy and its possible association with renal disease. METHODS: This was an observational study of a convenience sample of 38 chronic hypertensive pregnant women. The podocytes were labeled by the indirect immunofluorescence technique with anti-podocin and diamidino-phenylindole (DAPI). The count was made on 30 random fields analyzed and corrected according to urinary creatinine (podocytes/mg creatinine). The patients were assigned to two groups: NG (normal glomerular function), up to 100 podocytes, and GP (probable glomerulopathy), more than 100 podocytes. Urinary creatinine was measured by the alkaline picrate method. The variables analyzed were body mass index, gestational age, and systolic and diastolic blood pressure at the time of sample collection. Data were analyzed using the SPSS - version 16.0 (IBM - USA). Statistical analysis was performed by the χ2 test, and significant differences were considered when p<0.05. RESULTS: The median podocyte count was 20.3 (0.0-98.1) for group GN, and 176.9 (109.1-490.6) for GP. The mean body mass index was 30.2 kg/m2 (SD=5.6), mean gestational age was 35.1 weeks (SD=2.5), median systolic blood pressure was 130.0 mmHg (100.0-160.0) and median diastolic blood pressure was 80.0 mmHg (60.0-110.0). There was no significant correlation between podocyturia and body mass index (p=0.305), gestational age (p=0.392), systolic blood pressure (p=0.540) or diastolic blood pressure (p=0.540). CONCLUSIONS: In this study, there was no podocyturia pattern consistent with the presence of active renal disease, although some of the women studied (15.8%) exhibited a significant loss. We believe that it is premature to recommend the inclusion of the determination of podocyturia in routine prenatal clinical practice in chronically hypertensive pregnant women. .

Hypertensive emergencies of pregnancy.

Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent.

Increased urinary excretion of nephrin, podocalyxin, and ßig-h3 in women with preeclampsia.

Emerging evidence has shown that podocyte injury and reduced specific podocyte protein expressions contribute to proteinuria in preeclampsia. We collected urine specimens from women with preeclampsia to study whether podocyte-specific protein shedding is associated with renal barrier dysfunction. Urine specimens from women with normal pregnancies and from pregnant women complicated by chronic hypertension were used for comparison. We determined soluble podocyte slit protein nephrin levels in the urine specimens. Podocalyxin, ßig-h3, and VEGF concentrations were also measured. We found that nephrin and podocalyxin were barely detectable in the urine specimens from normal pregnant women and from women with chronic hypertension. In preeclampsia, urinary nephrin and podocalyxin concentrations were significantly increased and highly correlated to each other, r(2) = 0.595. Nephrin and podocalyxin were also correlated with urine protein concentrations. ßig-h3 was detected in the urine specimens from women with preeclampsia, and it is highly correlated with nephrin and podocalyxin concentrations in preeclampsia. ßig-h3 was undetectable in normal pregnancy and pregnancy complicated by chronic hypertension. Elevated VEGF levels were also found in women with preeclampsia compared with those of normal pregnancy and pregnancy complicated by chronic hypertension. These results provide strong evidence that podocyte protein shedding occurs in preeclampsia, and their levels are associated with proteinuria. The finding of urinary ßig-h3 excretion in preeclampsia suggests that increased transforming growth factor activity might also be involved in the kidney lesion in this pregnancy disorder.

The 24-hour urine collection: gold standard or historical practice?

OBJECTIVE: The objective of the study was to determine completeness of 24-hour urine collection in pregnancy. STUDY DESIGN: This was a retrospective laboratory/chart review of 24-hour urine collections at British Columbia Women's Hospital. Completeness was assessed by 24-hour urinary creatinine excretion (UcreatV): expected according to maternal weight for single collections and between-measurement difference for serial collections. RESULTS: For 198 randomly selected pregnant women with a hypertensive disorder (63% preeclampsia), 24-hour urine collections were frequently inaccurate (13-54%) on the basis of UcreatV of 97-220 micromol/kg per day (11.0-25.0 mg/kg per day) or 133-177 micromol/kg per day (15.1-20.1 mg/kg per day) of prepregnancy weight (respectively). Lean body weight resulted in more inaccurate collections (24-68%). The current weight was frequently unavailable (28%) and thus not used. For 161 women (81% proteinuric) with serial 24-hour urine levels, a median [interquartile range] of 11 [5-31] days apart, between-measurement difference in UcreatV was 14.4% [6.0-24.9]; 40 women (24.8%) had values 25% or greater, exceeding analytic and biologic variation. CONCLUSION: Twenty-four hour urine collection is frequently inaccurate and not a precise measure of proteinuria or creatinine clearance.

Serum and urine inhibin A but not free activin A are endocrine biomarkers of severe pre-eclampsia.

OBJECTIVE: Elevation of total serum inhibin A and activin A has been interpreted as evidence of placental dysfunction in women who develop pre-eclampsia. We sought to evaluate serum and urine levels of inhibin A and free activin A in normal and hypertensive pregnancies. STUDY DESIGN: Inhibin A and free activin A were measured by immunoassay in simultaneously collected serum and urine samples from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n = 11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams urine creatinine, and fractional excretions were calculated. RESULTS: Serum and urine inhibin A were increased and fractional excretion was decreased in pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in severe pre-eclampsia, compared with other gravidas. The only difference observed in free activin A was a decrease in serum free activin A in chronic hypertension, compared with severe pre-eclampsia and pregnant control women. Urine inhibin A showed the greatest discrimination between severe pre-eclampsia and pregnant control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity, 87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90 pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7-459.5) of a clinically indicated delivery due to pre-eclampsia. CONCLUSION: Serum and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin A may have application in the diagnosis and management of pre-eclampsia. Those with chronic hypertension have lower serum but not urine free activin A levels, compared with severe pre-eclampsia and mild pre-eclampsia.

Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia.

OBJECTIVE: Serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) are altered in women with clinical preeclampsia. We sought to identify whether similar alterations in urinary levels of these proteins cluster hypertensive disorders in pregnancy, and identify women with severe preeclampsia (sPE). STUDY DESIGN: Free urinary levels of sFlt-1, VEGF, and PlGF were measured by immunoassay in 68 women enrolled prospectively in the following groups: nonpregnant reproductive age (NP-CTR n = 14), healthy pregnant control (P-CTR n = 16), pregnant hypertensive and proteinuric women who did not meet criteria for severe preeclampsia (pHTN n = 21), and women with sPE (n = 17). RESULTS: There was no difference in gestational age at the time of enrollment among groups (median [range]: sPE: 31 [24-40], pHTN: 34 [16-40], P-CTR: 28 [7-39] wks). Urinary excretion of VEGF was significantly increased in sPE women compared with NP-CTR (P = .023), but did not differ among pregnant groups. Urinary PlGF levels were significantly increased in pregnant compared with nonpregnant women, but were decreased in all hypertensive women compared with healthy P-CTR (P < .001). Urinary sFlt-1 concentrations were significantly increased in women with sPE relative to all other groups (P < .001). pHTN women had higher sFlt-1 urinary output compared with P-CTR group (P = .001). A cutoff >2.1 in the ratio log [sFlt-1/PlGF] had 88.2% sensitivity and 100% specificity in differentiating women with sPE from normotensive controls. We also described that the log[sFlt-1/PlGF] ratio identified women with sPE better than proteinuria alone (P = .03). Our regression model revealed that uric acid correlated best with log[sFlt-1/PlGF] ratio (r = 0.628; P = .005). CONCLUSION: sPE is associated with increased urinary output of the antiangiogenic factor sFlt-1 and a decreased output of PlGF at the time of clinical manifestation, providing a rapid noninvasive screening of hypertensive women based on a sFlt/PlGF ratio. This ratio may be used as representation for severity of the disease, and appears to be superior to random urinary protein measurements.

Prostacyclin, thromboxane A and the effect of low-dose ASA in pregnancies at high risk for hypertensive disorders.

BACKGROUND: The aim of this study was to investigate the prostanoid production in pregnancies at high risk for hypertensive disorders, and the effect of low-dose acetylsalicylic acid (ASA) on prostanoids. MATERIAL AND METHODS: Ninety women with a bilateral notching in uterine arteries screened by Doppler ultrasound at 12-14 gestational weeks were randomized to the ASA (0.5 mg/kg/day) or placebo group. Forty-three women in both groups were followed up throughout the pregnancy. Urine samples were taken at baseline, and at 24-26 and 32-34 weeks of gestation to determine the urinary 11-dehydrothromboxane B(2) (u-11-dehydro-TxB(2)) and 2,3-dinor-6-keto-prostaglandin F(1alpha) (u-2,3-dinor-6-keto-PGF(1alpha)), the metabolites of thromboxane A(2) and prostacyclin, respectively. RESULTS: In the pregnancies with pregnancy-induced hypertension (PIH) before 37 gestational weeks, the 2,3-dinor-6-keto-PGF(1alpha)/11-dehydro-TxB(2) ratio did not increase as much as in other pregnancies (P = 0.028). In the placebo group pregnancies with preeclampsia had significantly lower 2,3-dinor-6-keto-PGF(1alpha) (P = 0.019) at 12-14 weeks of gestation compared to other pregnancies. In the placebo group the 2,3-dinor-6-keto-PGF(1alpha)/11-dehydroTxB(2) ratio remained unchanged throughout the pregnancy, with no significant difference between pregnancies with a normal or an adverse outcome. In the ASA group the 2,3-dinor-6-keto-PGF(1alpha)/11-dehydro-TxB(2) ratio increased (P < 0.001, early vs. midpregnancy). Again, the changes were similar in pregnancies with a normal or an adverse outcome. CONCLUSION: The balance of prostacyclin and thromboxane A(2) shifted in an unfavorable direction in pregnancies complicated by PIH. ASA had a favorable effect on the prostanoids.

[Renin aldosterone profile in essential hypertension during pregnancy and after delivery]. / Profil reninowo-aldosteronowy u kobiet z nadcisnieniem tetniczym pierwotnym w okresie ciazy i po porodzie.

BACKGROUND: The pathogenesis of essential hypertension (EH) is a complex multifactorial process. Little is known about the association between pregnancy and blood pressure fluctuation in women with EH. In this study we wanted to evaluate the relationship between the blood pressure (BP) and plasma renin activity (PRA) as well as serum and urine aldosterone (ALDO) levels in pregnant women with essential hypertension. MATERIALS AND METHODS: We analyzed 84 pregnant women (97% primigravida) with EH aged 22-40 (mean 29.5 +/- 5.4) years and 60 healthy pregnant women aged 22-40 (mean 28.5 +/- 4.9) years. In women with EH, antihypertensive therapy was stopped immediately after pregnancy was confirmed. Patients with EH were divided to two groups: 1) with BP > or = 140/90 and 2) with BP > or = 140/90. PRA and ALDO as well as sodium and potassium excretion were measured three times in different periods of pregnancy: 8-12 weeks, 24-28 weeks, 34-38 weeks. In addition, both PRA and ALDO were analyzed in 4th month after delivery i.e. in the time, in which woman is reached hormonal and hemodynamic stability. PRA and ALDO were determined by RIA methods. BP was monitored by standardized method using mercury manometer. RESULTS: PRA and ALDO concentrations in both: serum and urine were increased during pregnancy in all studied groups. No difference in kinetics of PRA and ALDO was stated between healthy pregnant women with EH. Increased was observed in women and during pregnancy. Statistically significant, the highest level of PRA was noted in fourth month after delivery in women with BP > 140/90. In this period, however, concentrations of ALDO in both serum and urine were the same in all examined women. CONCLUSION: 1. In women with EH and BP < 160/100 mm Hg during pregnancy PRA and concentration of ALDO in serum as well as ALDO excretion were the same as in healthy pregnancy women. 2. Reduction of blood pressure was observed in the group of women with the lowest PRA in fourth month after delivery. 3. PRA measured in women with EH may be a predictive parameter of BP during pregnancy.

A prospective study of the impact of automated dipstick urinalysis on the diagnosis of preeclampsia.

OBJECTIVE: To determine prospectively in hypertensive pregnant women 1) the accuracy of dipstick testing for proteinuria using automated urinalysis, 2) factors that might affect such accuracy, and 3) the potential impact of automated dipstick testing on the accuracy of diagnosis of preeclampsia according to acceptance of proteinuria at either 1 + or 2 + level. DESIGN: Prospective study. SETTING: Antenatal day assessment unit and antenatal ward of St George Hospital, a teaching hospital in Sydney, Australia. POPULATION: 170 hypertensive pregnant women attending as outpatients or inpatients. METHODS: 503 midstream urine samples were collected prospectively on separate occasions from 170 women. Full urinalysis was recorded using the Bayer Clinitek 50 automated urinalysis device and Multistix 10SG urinalysis strips (Bayer Diagnostics, Victoria, Australia). Each MSU was analysed for spot protein/creatinine ratio and also for culture and sensitivity if symptoms of a urinary tract infection were present or dipstick included positive nitrites. Urinalysis protein results were compared with spot urinary protein/creatinine ratio (previously shown to correlate with 24-hr urine protein excretion) to determine the accuracy of urinalysis. True proteinuria was defined as a ratio >/= 30 mg protein/mmol creatinine. RESULTS: False positive dipstick tests ranged from 7% at 3 + level to 71% at 1 + proteinuria level while false negative rates were 7% for "nil" and 14% for "trace" proteinuria, 9% overall. Accepting the dipstick proteinuria result at face value led to an incorrect diagnosis of preeclampsia or gestational hypertension in 85 (50%) women. Dipstick proteinuria was significantly more likely to be correct (true positive/true negative) if diastolic blood pressure was elevated > 90 mmHg (p = 0.032) and in the absence of ketonuria (p = 0.001). Accepting a diagnosis of preeclampsia on the basis of de novo hypertension and dipstick testing alone was accurate less often (70%) when > 1 + was used as a discriminant value than at the 82% of presentations when > 2 + was used (p = 0.001). CONCLUSION: Accepting "nil" or "trace" proteinuria as a true negative dipstick results fails to identify approximately 1 in 11 hypertensive pregnant women with true proteinuria, a false negative rate that may be acceptable provided these women are subject to ongoing vigilant clinical review. Even with automated urinalysis the false positive rate for dipstick levels >/= 1 + is very high, particularly in the presence of ketonuria and relying on this alone to diagnose preeclampsia leads to significant errors in diagnosis. Accepting >/= 2 + dipstick proteinuria improves overall diagnostic accuracy for preeclampsia at the expense of a higher false negative rate. This study emphasizes the need to confirm dipstick proteinuria with a further test such as a spot urine protein/creatinine ratio in all hypertensive pregnant women, particularly in research studies.

Random urine protein-creatinine ratio to predict proteinuria in new-onset mild hypertension in late pregnancy.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of random urine protein-creatinine ratio for prediction of significant proteinuria (> or = 300 mg/24 h) in patients with new-onset mild hypertension in late pregnancy. METHODS: Medical records of 185 consecutive pregnant patients with new onset of mild hypertension in late pregnancy were reviewed. Random urine samples were taken before 24-hour urine collection. The predictive values of the random urine protein-creatinine ratio for diagnosis of significant proteinuria were estimated by using at least a 300-mg protein level within the collected 24-hour urine as the gold standard. RESULTS: Thirty-nine patients (21%) had significant proteinuria. There was a significant association between 24-hour protein excretion and the random urine protein-creatinine ratio (rs = 0.56, P <.01). With a cutoff protein-creatinine ratio greater than 0.19 as a predictor of significant proteinuria, sensitivity and specificity were 85% and 73%, respectively. Positive and negative predictive values of the test were 46% and 95%, respectively. CONCLUSION: The random urine protein-creatinine ratio was a poor predictor for significant proteinuria in patients with new-onset mild hypertension in late pregnancy.

[Hypocalciuria during pregnancy as a risk factor of preeclampsia]. / Hipocalciuria durante el embarazo como factor de riesgo de preeclampsia.

BACKGROUND: Although preeclampsia has been studied thoroughly, its origin is still unknown. However, there are various factors that strive to explain its cause. Some of them are: the genetic, placenta and immunological aspects, endothelial damage, hormonal and autoimmunological alterations, deficit of essential fatty acids, and the ion disorder theory. OBJECTIVE: To evaluate if hypocalciuria is a factor related to the development of preeclampsia or transitory hypertension during pregnancy. MATERIAL AND METHOD: A cohort study of 63 women was performed. Serum calcium levels and calcium in 24 hours urine collection were assessed in women with 32 to 36 weeks of pregnancy. Patients were selected by sampling of consecutive cases. RESULTS: Twenty-four patients had hypocalciuria (group I) and 39 normocalciuria (group II). Calcium serum levels were of 8.05 +/- 0.22 mg/ dL and of 8.22 +/- 0.36 for group I and II, respectively (t=1.25, p=0.21). Of the 24 patients with hypocalciuria, 5 (20.83%) had preeclampsia compared to 2 (5.12%) of the 39 with normocalciuria (RR= 4.06; 95% CI 3.29, 7.20). We did not find correlation between preeclampsia and the risk factors. When considering hypocalciuria as a prognosis test, we obtained 0.71 of sensitivity and 0.66 of specificity; the exactitude of the test was of 0.66. CONCLUSIONS: Hypocalciuria could be considered as a risk factor for the development of preeclampsia and transitory hypertension during pregnancy.

[Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion in women with pregnancy complicated with hypertension]. / Aktywnosc N-acetylo-beta-D-glukozaminidazy (NAG) w moczu u kobiet w ciazy powiklanej nadcisnieniem tetniczym.

OBJECTIVES: Hypertensive disorders in pregnancy are one of the major mortality risk factors for mother and fetus. Although pathomechanisms of hypertension are extreme complex, the involvement of kidneys usually occurs. N-acetyl-beta-D-glucosaminidase (NAG) is a lysosomal enzyme which is located in renal tubular cells. Therefore an elevation of urinary NAG activity serves as a marker of tubular cell damage. AIM: Evaluation of renal tubular damage in pregnant women with different types of hypertension by determination of urinary NAG activity. MATERIAL AND METHODS: The study comprised 84 pregnant women in third trimester, divided according to type of hypertension into 3 subgroups: pregnancy induced hypertension (n = 58), preeclampsia (n = 13) and chronic hypertension (n = 13). The control group comprised 36 healthy pregnant women. Urinary NAG activity was measured in the second morning urine samples by colorimetric method and the results were expressed as NAG/creatinine ratios (NAG/Cr). RESULTS: The highest NAG/Cr ratios were found in women with preeclampsia (median-1.520 U/mmol) and in women with pregnancy induced hypertension (median-0.874 U/mmol) and both results differed significantly from those in controls (median-0.782 U/mmol). There was slight positive correlation between NAG/Cr ratios and systolic blood pressure (r = 0.225, p < 0.05). CONCLUSIONS: Hypertension in pregnancy may lead to renal tubular damage, however clinical significance of this phenomenon requires further studies.

9 alpha,11 beta-prostaglandin F2 in pregnancies at high risk for hypertensive disorders of pregnancy, and the effect of acetylsalicylic acid.

Our purpose was to determine urinary 9 alpha,11 beta-prostaglandin F2, the primary metabolite of prostaglandin D2, in pregnancies at high risk for hypertensive disorders and the effect of acetylsalicylic acid on 9 alpha,11 beta-prostaglandin F2. Ninety high risk women were randomised to acetylsalicylic acid and placebo groups at 12-14 weeks of gestation, with 43 women in both groups followed up successfully. 9 alpha,11 beta-prostaglandin F2 was determined at baseline, at 24-26, and at 32-34 weeks of gestation. Fifteen normotensive non-pregnant women, 17 normotensive pregnant women at 12-14, and 15 at 30-34 weeks of gestation served as controls. Urinary 9 alpha,11 beta-prostaglandin F2 was significantly higher in pregnant women at 12-14 weeks of gestation as compared to non-pregnant women. High risk pregnancies had higher 9 alpha,11 beta-prostaglandin F2 as compared to normotensive pregnancies at 12-14, and at 30-34 weeks of gestation. Urinary 9 alpha,11 beta-prostaglandin F2 increased throughout pregnancy unrelated to the outcome of the pregnancy or to the treatment.

Chronic exogenous hyperinsulinaemia-induced hypertension in pregnant rats: effect of chronic treatment with l-arginine.

Recent studies have shown that maternal hyperinsulinaemia is a risk factor for the development of hypertension in pregnancy. Experimentally, pregnant rats with chronic exogenously induced hyperinsulinaemia (P-INS rats) have increased blood pressure at the end of gestation. This is associated with a blunted elevation of the excretion of the urinary metabolites of nitrate (UNO(x)). In the present study, we aimed to evaluate the mechanism(s) of the increase in blood pressure in this model. Four groups were studied: normal pregnant rats (P rats), P-INS rats, P-INS rats treated with L-arginine (2 g/l in the drinking water) (L-ARG rats) and hyperinsulinaemic virgin rats (V-INS rats). Systolic blood pressure (SBP), UNO(x) excretion (on ingestion of a controlled low-nitrate diet), urine noradrenaline (norepinephrine) and plasma endothelin levels were evaluated. Rats were killed on day 22 of pregnancy. Five P-INS rats were not killed at this time, in order to measure SBP 30 and 60 days after delivery. Fetal number and fetal body weight were evaluated. At the end of pregnancy, a 10+/-3% increase in SBP was found in P-INS rats, contrasting with a fall of -15+/-4% in P rats (P<0.01). In the L-ARG group at the end of pregnancy, SBP values had fallen by -14+/-2%, to values comparable with those of P rats. The increase in UNO(x) excretion was 175+/-38% in P rats, 106+/-12% in L-ARG rats and 41+/-8% in P-INS rats (P<0.01 compared with P and L-ARG groups). No differences were found in the urinary excretion of noradrenaline or in the plasma levels of endothelin-1 between the pregnant groups. Fetal number was similar in all groups, but fetal body weight was lower for P-INS rats compared with P and L-ARG rats. Thus the blood pressure response to L-arginine strongly suggests that a decrease in NO availability may be the main pathogenic mechanism involved in the development of hypertension in this model.

Effect of concentration and biochemical assay on the accuracy of urine dipsticks in hypertensive pregnancies.

OBJECTIVE: To assess how urine concentration and biochemical assay influence the assessment of proteinuria. METHODS: This was a prospective study to assess the accuracy of detection and quantification of proteinuria within the day assessment unit and antenatal ward of a teaching hospital in Leicester, United Kingdom. We studied hypertensive pregnancies (of mixed parity) referred to day care assessment or attending the antenatal hypertension clinic after 20 completed weeks of gestation (n = 197). Aliquots of a well-mixed 24-h urine collection were tested by routine dipstick urinalysis and then assayed for protein using the Benzethonium Chloride and the Bradford assays (n = 197). MAIN OUTCOME MEASURES: Total protein excretion in 24 h and protein concentration per liter of urine for both biochemical assays were compared to semiquantitative dipstick protein measurement. RESULTS: The prevalence of proteinuria in the study group varied according to the method used for testing. Dipstick urinalysis recorded the lowest prevalence (16.2%) and the Benzethonium Chloride assay measuring total protein excretion in 24 h recorded the highest (70.1%). When the positive and negative predictive values for dipstick urinalysis were calculated, performance was found to be dependent on both the units of measurement compared and the type of assay used as the "gold standard." Positive predictive values ranged from 87.5% to 96.9% and negative predictive values ranged from 35.2% to 92.1%. CONCLUSIONS: The prevalence of proteinuria in hypertensive pregnancies is dependent on the method used to detect it. The amount of protein assessed quantitatively is further dependent on the biochemical assay employed. However, regardless of the quantitative assessment, dipstick urinalysis has a significant false-negative rate. This first reporting of a variation in performance between dipstick urinalysis and two different biochemical assays in pregnancy may be explained in relation to protein assay specificity and the observed protein compositions of the samples on electrophoretic analysis. The significance of proteinuria should be considered in light of the method used to detect it, but, ultimately, it must be related to clinical outcome.