Fetal serum concentrations of cystatin C and beta2-microglobulin as predictors of postnatal kidney function

OBJECTIVES: Cystatin C and beta(2)-microglobulin are established serum markers of renal function in children and adults. In contrast to creatinine, diaplacental exchange is minimal. The aim of the study was to establish reference values in fetal serum and to test their efficiency in predicting postnatal kidney function. STUDY DESIGN: This was a prospective noninterventional study measuring cystatin C and beta(2)-microglobulin by particle-enhanced immunoturbidimetry in excess serum from 129 cordocenteses performed in 84 fetuses. Reference intervals (mean +/- 1.96 SD) were calculated in a subgroup of 54 fetuses without evidence of kidney disease, and these reference values were evaluated in 75 sera from 55 fetuses. RESULTS: Mean cystatin C was 1.66 +/- 0.202 mg/L (upper limit 2.06), and mean beta(2)-microglobulin was 4.25 +/- 0.734 mg/L. Unlike cystatin C, beta(2)-microglobulin decreased significantly with gestational age so that the upper reference limit was 7.19-0.052 x gestational age in weeks. beta(2)-Microglobulin had higher sensitivity (90.0% vs 63.6%) and cystatin C a higher specificity (91.8% vs. 85.5%) for the prediction of impaired renal function; diagnostic efficiency was equal (87.6% vs. 86.1%). Fetuses with impaired renal function at birth or who were aborted for renal malformations had higher cystatin C concentrations than those in a control group. beta(2)-Microglobulin was increased only in fetuses who were aborted. CONCLUSION: Fetal serum cystatin C and beta(2)-microglobulin concentrations may be useful predictors of postnatal kidney function.     

Fetal hyperechogenic kidney with normal amniotic fluid volume: a diagnostic dilemma

OBJECTIVE: To determine the prognostic value of sonographically detected fetal hyperechogenic kidneys with normal amniotic fluid volume. METHODS: Seven cases of hyperechogenic fetal kidneys were identified by sonography over a 7-year period (1996--2002). Increased renal echogenicity was diagnosed when the renal parenchyma was of greater echogenicity than adjacent liver tissue. Amniotic fluid volume was measured by the semiquantitative sonographic technique known as the amniotic fluid index (AFI). RESULTS: Three of the live-born infants had autosomal dominant polycystic kidney disease and one had autosomal recessive polycystic kidney. In the remainder, autopsy study revealed multifocal renal dysplasia in two cases and normal kidneys in one. CONCLUSIONS: Increased renal echogenicity with normal amniotic fluid volume in a fetus without other anomalies is a difficult diagnostic dilemma. Although it is usually indicative of renal parenchymal disease with possible renal failure after birth or in early childhood, in some cases, it represents a normal variant. .     

Prenatal ultrasound,genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases

Purpose

To investigate the sonographic and clinical genotype–phenotype correlations in autosomal recessive polycystic kidney disease (ARPKD) and other cystic kidney diseases (CKD) in a large cohort of prenatally detected fetuses with hereditary CKD.

Methods

We retrospectively studied the clinical and diagnostic data of 398 patients referred with prenatal ultrasound findings suggestive of CKD between 1994 and 2010. Cases with confirmed hereditary CKD (n = 130) were analyzed as to their prenatal ultrasound findings, genotype, and possible predictors of clinical outcome.

Results

ARPKD was most common in our non-representative sample. Truncating PKHD1 mutations led to a significantly reduced neonatal prognosis, with two such mutations being invariably lethal. Sonographically visible kidney cysts occurred in only 3% of ARPKD cases. Renal abnormalities in Meckel syndrome (MKS) appeared earlier than in ADPKD (19.6 ± 3.7 vs. 29.8 ± 5.1 GW) or ARPKD (19.6 ± 3.7 vs. 30.2 ± 1.2 GW). Additional CNS malformations were not found in ARPKD, but were highly sensitive for MKS. Pulmonary hypoplasia, oligo/anhydramnios (OAH), and kidney enlargement were associated with a significantly worse neonatal prognosis.

Conclusion

Genotype, sonographic signs of OAH, enlarged kidney size, and pulmonary hypoplasia can be useful predictors of neonatal survival. We propose sonographic morphological criteria for ARPKD, ADPKD, MKS, and renal cyst and diabetes syndrome (RCAD). We further propose a clinical diagnostic algorithm for differentiating cystic kidney diseases.

     

Feto-amniotic shunting for lower urinary tract obstruction (LUTO)--a case report

Posterior urethral valves are the main cause of fetal lower urinary tract obstruction (LUTO) with typical sonographic signs like urinary tract dilatation and reduction of amniotic fluid. LUTO is associated with a high rate of perinatal mortality and is the main cause of kidney failure in early childhood. In such cases vesico-amniotic shunting is a common but risky procedure of fetal surgery to prevent anhydramnion and lethal lung hypoplasia. This case report demonstrates that lung hypoplasia can be prevented by vesico-amniotic shunting of the fetal megacytis in the 23rd week of gestation in a fetus with lower urinary tract obstruction and anhydramnion. The prenatal measured concentration of cystatin C in the fetal urine correlated with the postnatal impaired kidney function. The indication and therapeutic benefit of vesico-amniotic shunting remain controversially discussed in the literature because until today there is no evidence for a reduction in perinatal or long-term morbidity due to early fetal kidney damage. The earlier ultrasound detection of LUTO during the first trimester of pregnancy proposes the possibility of earlier intervention and protection of nephrogenesis. First case studies about first trimester vesico-amniotic shunting have been published; the influence on the postnatal kidney function merits further well-structured investigation.     

Cystatin C in pre-eclampsia

Objective: To evaluate diagnostic value of cystatin C serum levels as alternative marker of renal function in pre-eclamsia (PE) and compare it with the traditional markers of renal function, creatinine and uric acid. In order to investigate the possible influence of inflammation on biochemical markers of renal function, serum levels of high sensitive CRP were measured (hsCRP). Methods: In this prospective study markers of kidney function were investigated in two groups of pregnant women: one with PE (n?=?32) and the other of healthy pregnant women (n?=?60). Serum cystatin C levels were measured as well as levels of traditional renal markers creatinin and uric acid and levels of high sensitive C-reactive protein. Results: Serum levels of cystatin C, creatinine and uric acid were significantly higher in the PE group than in the control group. Serum levels of hsCRP were higher in approximately the same number of patients with PE (50%) as in normal pregnancies (40%), without significant differences in CRP values between the two groups of patients. Conclusions: Cystatin C serum level may have significant role as a marker of pre-eclampsia specially when used in combination with uric acid levels.     

Serum cystatin C in pregnancies with normal and restricted fetal growth

The objective of this study was to investigate circulating levels of cystatin C (an important endogenous marker of renal function) in mothers, fetuses, and neonates from intrauterine growth-restricted (IUGR; characterized by impaired nephrogenesis) and appropriate-for-gestational-age (AGA) pregnancies. Serum cystatin C levels were measured by enzyme immunoassay in 40 parturients and their 20 IUGR (or= 0.376 and P 相似文献   

Prenatal diagnosis of nonmosaic trisomy 9 in a fetus with severe renal disease.

We report a case of nonmosaic trisomy 9 presenting at 21 weeks of gestation with polycystic, echogenic horseshoe kidney, collapsed bladder, absent amniotic fluid, and intrauterine growth restriction. Color Doppler imaging demonstrated no blood flow signals from renal vessels. Fetal blood sampling confirmed a 47,XX,+9 karyotype, with no evidence of mosaicism, and increased serum beta2-microglobulin levels of 10.7 mg/l, consistent with severe renal failure. A repeat scan at 23 weeks also revealed a dysmorphic face, bilateral microphthalmia, and a cerebellar vermian defect. Follow-up examinations showed progressive growth restriction leading to fetal death at 33 weeks of gestation. This report demonstrates that fetuses with nonmosaic trisomy 9 may present with severe renal abnormalities and confirms that cases seen in the second and third trimesters usually have a dismal outcome.     

Prenatal evaluation of fetal renal function based on serum beta(2)-microglobulin assessment

The relationship between fetal renal function (FRF) and fetal serum beta(2)-microglobulin (B2MG) was investigated by comparing its value in 112 unaffected fetuses with that of 23 fetuses presenting with urinary tract malformations (UTM). Fetal serum level of B2MG was totally unrelated to gestational age; its value increased in cases of severe impairment of FRF but was similar to controls in all mild uropathies (p<0.05). Evaluating serum B2MG could be beneficial in fetuses with severe renal damage, but is of no use in unilateral UTM since only the global FRF is tested and not the function of each single kidney.     

Oxytocin secretory response to breast stimulation in pregnant women

Infantile polycystic kidney disease in an autosomal recessive disorder which in its severe form is characterized by bilateral renal enlargement and renal failure. The present study was undertaken to assess the diagnostic accuracy of antenatal sonography in a population at risk. Nineteen patients with fetuses at risk for infantile polycystic kidney disease were referred for ultrasound examination to the Perinatal Unit at Yale-New Haven Hospital. Ten infants had infantile polycystic kidney disease (53%). A positive antenatal sonographic diagnosis was made by the presence of oligohydramnios, an absent urinary bladder, bilateral renal enlargement as measured by the kidney circumference-to-abdominal circumference ratio, and the typical hyperechogenic appearance of the kidneys in the disease. A correct antenatal diagnosis was made in nine of the 10 affected infants. There were no false positive diagnoses. A false negative diagnosis occurred in an infant with a less severe form of the disease. Ultrasound is a valuable tool in the antenatal diagnosis of infantile polycystic kidney disease.     

B超检查胎儿肾脏回声增强的临床意义

目的探讨B超检查胎儿肾脏回声增强的临床意义。方法选择31例产前B超发现胎儿肾脏回声增强的患者,征求本人意见,对选择引产放弃胎儿者（12例）行引产后患儿尸体解剖;对选择继续妊娠者（19例）定期随访。分娩时取胎儿脐带血进行胎儿染色体分析。结果（1）31例中6例胎儿同时合并其他脏器异常,3例胎儿合并染色体异常,2例患者具有家族史。（2）12例选择终止妊娠者中,10例伴羊水过少;B超检查胎儿肾脏回声增强的原因分别为婴儿型多囊肾10例、成人型多囊肾1例和多囊性肾发育不良1例。（3）19例选择继续妊娠者中,2例羊水过少患儿于新生儿期死亡,病理解剖结果为婴儿型多囊肾;3例患儿分别在出生后1岁内死亡,病理诊断分别为婴儿型多囊肾或多囊性肾发育不良;1例患儿在出生后26个月出现高血压症状,肾功能异常,诊断为婴儿型多囊肾;4例患儿出生后B超检查肾脏回声转为正常;9例肾脏B超表现与产前检查相同,但目前没有任何临床症状。结论（1）胎儿期肾脏B超回声增强的原因多为婴儿型多囊肾、肾发育不良和非特异性肾病,也有部分为正常肾脏变异。（2）羊水量是判断胎儿预后的关键指标之一,当胎儿期肾脏回声增强伴羊水过少时提示胎儿预后不良。（3）当发现肾脏B超回声增强时,应仔细询问家族史,并对胎儿父母肾脏及胎儿其他部位进行详细检查,必要时建议进行胎儿染色体核型分析。     

Predictive value of amniotic fluid cystatin C levels for the early identification of fetuses with obstructive uropathies

Objective To compare the diagnostic accuracy of cystatin C with that of creatinine in discriminating renal function in fetuses without ultrasononographic evidence of renal malformations from those with obstructive uropathies.
Design Prospective, observational cohort study.
Setting Prenatal morphologic and functional evaluation of fetal obstructive uropathies throughout pregnancy.
Population A total of 96 healthy pregnant women at different stages of pregnancy, without any pregnancy-related maternal disease. Eighty-one pregnant women without clinical and ultrasonographic evidence of any fetal anomaly, confirmed at birth, were defined as controls; 15 pregnant women with various fetal obstructive uropathies, evidenced by repeated ultrasound examinations and confirmed at birth, were defined as cases.
Methods Creatinine was measured by a kinetic Jaffe picric acid method and cystatin C by a nephelometric immunoassay. Variables were analysed by applying conventional statistical tests; the non-parametric receiver operating curves (ROC) analysis was used to evaluate the diagnostic efficiencies of the biochemical markers.
Main outcome measures Incidence of confirmed, diagnosed, neonatal obstructive uropathy by measuring baseline levels of cystatin C and creatinine in amniotic fluid.
Results Baseline levels of cystatin C in amniotic fluid were significantly higher (   P = 0.0015  ) among cases than in controls with comparable gestational age; no significant difference was found for creatinine levels (   P = n.s.  ). The maximum diagnostic accuracy of serum cystatin C in discriminating controls from fetal uropathies was 96%, while that of creatinine was 62%.
Conclusion Cystatin C may be considered a sensitive biochemical marker for the early identification of fetuses with obstructive uropathies.     

Ultrasound diagnosis and perinatal management of fetal genito-urinary abnormalities

Approximately 50% of fetal abdominal masses originate in the urinary system and those recognizable ultrasonically include renal dysplasia, renal agenesis and obstruction of the lower excretory channels. Fetal renal anomalies may be discovered co-incidentally during the course of sonographic evaluation of uterine size-dates discrepancy, because they are commonly associated with fetal growth retardation and/or oligohydramnios, or during a planned sonographic follow-up of pregnancies in patients who are at risk of recurrence of such anomalies. The sonographic demonstration of renal anomalies under these circumstances may allow for elective termination of pregnancy, may modify the obstetric management and/or facilitate pediatric and surgical care of the newborn. In the collaboration study at three ultrasonic centers there were 81 cases of genito-urinary tract anomalies detected antenatally in a five years period. Among the detected anomalies there were 30 hydronephrotic fetuses, 12 with multicystic disease, 15 with Potter's syndrome, 10 with polycystic kidney, 9 with Prune Belly syndrome, 4 with isolated renal cysts and 1 with an ovarian cyst. Perinatal management of the fetus with urinary tract abnormalities greatly depends on the accuracy of the diagnosis. It would be justifiable to suggest that an inexperienced observer should not make the final diagnosis. He could be of great help, if one kept a high index of suspicion in patients with a significant family history of oligohydramnios and of unexplained abnormal cystic structures in the fetal abdomen and seek the help of a special referral center where experience in related cases is concentrated. Once an accurate diagnosis is made, various alternatives are open to the obstetrician. This is primarily dependent upon the type and degree of the abnormality. Unilateral multicystic kidney and hydronephrosis due to obstruction above the level of the urethra appear to be compatible with extrauterine life and should be approached accordingly. If there is massive enlargement of the fetal abdomen, elective cesarean delivery should be considered to prevent the dystocia which may occur with vaginal delivery and to prevent further damage of these vital organs. If bilateral renal agenesis, bilateral multicystic kidneys, or bilateral infantile polycystic kidneys are demonstrated early in gestation, the obstetrician and parents may choose to terminate the pregnancy because these conditions are not compatible with extrauterine life.(ABSTRACT TRUNCATED AT 400 WORDS)     

The nonpredictive value of fetal urinary electrolytes: preliminary report of outcomes and correlations with pathologic diagnosis

Fetal urine was sampled 12 times in nine fetuses with sonographically diagnosed urinary tract obstruction to assess renal function. By previously proposed criteria, four fetuses were predicted to have poor renal function. Two of these fetuses were found to have renal dysplasia on autopsy after elective termination. The other two died in the neonatal period but only one of these had histologic evidence of renal dysplasia. Five fetuses were predicted to have good renal function. Three of these developed renal failure after birth, one was found to have renal dysplasia on autopsy after elective termination, and one is alive and well. We conclude that fetal urine electrolytes are not necessarily an accurate predictor of neonatal renal function.     

Serial amnioinfusions for fetal pulmonary palliation in fetuses with renal failure

Fetal lower urinary tract obstruction (LUTO) encompasses a heterogeneous group of congenital pathologies and generally results in oligohydramnios. Fetal intervention (e.g. vesicoamniotic shunting, fetal cystoscopy) has traditionally been reserved for cases with a favorable renal profile, while those with unfavorable renal function have been offered termination or expectant management with the latter leading to high incidence of marked pulmonary hypoplasia, neonatal morbidity and mortality. Here, we describe two cases, which were not candidates for traditional intervention based on abnormal fetal renal function, who elected to proceed with serial amnioinfusions for fetal pulmonary palliation to attenuate the risk of pulmonary hypoplasia.     

Cystatin C, beta-2-microglobulin and beta-trace protein in pre-eclampsia

BACKGROUND: An altered renal function is an essential component of the patho-physiology of pre-eclampsia. The plasma levels of low molecular mass proteins, e.g. beta-trace protein, beta-2-microglobulin and cystatin C, are increased in the third trimester of normal pregnancy. The plasma levels of cystatin C and beta-2-microglobulin are further increased in pre-eclampsia, and the cystatin C level has been reported to be a reliable marker for the disease. The aim of this investigation was to study the plasma levels of beta-trace protein, beta-2-microglobulin and cystatin C in pre-eclampsia, and to determine the diagnostic performance of these proteins compared to that of urate and creatinine. METHODS: A case-control study of 57 women diagnosed with pre-eclampsia, and 218 healthy women with uncomplicated singleton pregnancies in the third trimester. Women in the catchment area of Lund, Sweden, were included during an 18-month period from October 2003 to April 2005. Venous blood samples were drawn upon inclusion when diagnosis was made. The maternal plasma concentrations of the 3 proteins were analysed by automated particle-enhanced immunoturbidimetric assays. RESULTS: The plasma levels of the 3 proteins were significantly higher in the third trimester of pre-eclamptic patients compared to healthy pregnant women in the third trimester. The upper reference limits (parametric 97.5 percentile) were 2.57 mg/l for beta-2-microglobulin, 0.72 mg/l for beta-trace protein and 1.37 mg/l for cystatin C. ROC analysis showed similar diagnostic performance for the 3 proteins, with beta-trace protein displaying the best diagnostic performance of all the analytes. CONCLUSIONS: In this study, the maternal plasma levels of beta2-microglobulin, beta-trace protein and cystatin C were all significantly elevated in pre-eclampsia compared to those of healthy pregnant women, and displayed similar diagnostic performance for diagnosing pre-eclampsia. The results indicate that low molecular mass proteins are useful as markers of renal impairment in pre-eclampsia.     

Non-syndromic association of congenital hepatic fibrosis and bilateral cystic renal dysplasia.

Congenital hepatic fibrosis (CHF) is associated with autosomal recessive polycystic kidney disease (ARPKD). Although cystic renal dysplasia (CRD) is the most common form of newborn cystic renal disease, this disorder of anomalous metanephric differentiation is only rarely found concurrent with CHF. Our literature review found only 13 sporadic and 12 familial non-syndromic cases of combined bilateral CRD and CHF reported outside Taiwan. We report the first domestic case, occurring in a fetus of 18 weeks' gestational age, which was the second pregnancy of a 24-year-old mother with a previous history of spontaneous abortion at 10 weeks' gestational age. Postmortem autopsy confirmed the concurrence of bilateral CRD and CHF without associated anomalies of other visceral organs and external appearance. This particular association must be differentiated from ARPKD and liver disease, in regard to ultrasonographic examination and genetic counseling.     

Prenatal diagnosis and postnatal outcome of congenital megalourethra. Report of two cases

We present 2 cases of congenital megalourethra diagnosed by prenatal ultrasound scan during the second trimester of pregnancy. The first one was associated with features suggesting prune belly syndrome (PBS) in contrast to the other one. Fetal urine biochemistry and fetal serum beta2-microglobulin was used to rule out severe renal impairment that would have led to postnatal renal failure soon after birth. In both cases, after extensive counselling, the parents opted against termination of pregnancy and in both cases vaginal delivery of a live neonate occurred. Postnatal follow-up demonstrated that the two infants were found to have mildly altered renal function without any physical or mental development delay. Association with features of PBS didn't seem to influence the severity of renal function impairment however, but PBS may influence parents' decision regarding termination because of additional corrective surgery and further infertility.     

Prenatal diagnosis of autosomal recessive polycystic kidney disease by ultrasonography and magnetic resonance imaging.

Autosomal recessive polycystic kidney disease is a relatively rare congenital disease affecting the kidneys and liver. We noticed the kidney abnormality at 22 weeks gestation and observed the patient till the delivery at 36 weeks of gestation. The ultrasonographic features consisted of bilaterally enlarged hyperechogenic kidneys, oligohydramnios, lack of distention and difficulty in identifying the fetal urinary bladder. The serial sonographic features of the kidneys changed as pregnancy progressed. The kidney cysts gradually changed in size, shape and renal texture, but the umbilical velocimetry and the kidney circumference/abdominal circumference ratio did not change. Magnetic resonance imaging also showed similar characteristic features as observed by ultrasonography.     

Prenatal sonographic patterns in six cases of Wolf-Hirschhorn (4p-) syndrome

This multicentric study presents 6 cases of Wolf-Hirschhorn syndrome (deletion of 4p) detected after a sonographic prenatal diagnosis of early intrauterine growth retardation with fetal abnormalities. Standard karyotyping on regular G-banding during pregnancy was normal in half of the cases. Fortunately, the associated sonographic signs of a typical face, cystic cerebral lesions, midline fusion defects and bilateral renal hypoplasia may help to refine specific indications for high-resolution banding and molecular analysis by in situ hybridization.