Prenatal diagnosis and outcome of unilateral multicystic kidney.

We reviewed the records of 144 patients. The mean gestational age at first US diagnosis was 27.5 ± 4.3 weeks. An anomaly of the contralateral kidney was detected in 25% of cases. An extrarenal anomaly was detected in 13.8%. Karyotype analysis was performed in 16.6% of cases and revealed trisomy 18 in 2 cases with extrarenal defects. Karyotype analysis was normal in all the patients who had isolated multicystic dysplastic kidney (MCDK). The diagnostic accuracy of prenatal ultrasound was 92.2%. Contralateral kidney anomaly was detected 33.9% of patients, and half of these were vesicoureteral reflux. Antihypertensive therapy was required in 2.6% of cases. Nephrectomy was performed in 8%, and partial or total involution of MCDK was achieved in 33.9% of patients. MCDK can be accurately diagnosed by prenatal sonography, and prognosis depends on extrarenal and contralateral renal abnormalities. In isolated cases, require of surgery is rare, and serial follow-up is suggested to determine involution.Impact statementWhat is already known on this subject? Multicystic dysplastic kidney (MCDK) is one of the most renal anomalies and is associated with numerous renal and extrarenal abnormalities. It can lead to severe consequences in the neonatal period.What do the results of this study add? The accuracy of prenatal ultrasonography is excellent for detecting MCDK. In isolated unilateral cases, chromosomal aberrations are low, and the majority of them involute spontaneously. A periodic follow-up of the contralateral kidney is mandatory due to an increased risk of an anomaly. Genital anomaly risk is increased in males.What are the implications of these findings for clinical practice and/or further research? Detailed evaluation and follow-up of the contralateral kidney are crucial for counselling in isolated cases. Karyotype analysis in isolated unilateral MCDK is debateable. Postnatal prognosis is encountering, and the majority of patients have no requirement of surgery.

Outcomes of prenatally diagnosed solitary functioning kidney during early life.

OBJECTIVE: To evaluate outcomes of congenital solitary functioning kidney (SFK) in early childhood. STUDY DESIGN: A retrospective study of 32 children diagnosed in utero with SFK owing to unilateral renal agenesis or multicystic dysplastic kidney and followed for 1 to 11.5 years. RESULTS: SFK length was in the compensatory hypertrophy range in 45% of fetal sonographic evaluations from mid-pregnancy, and in 85% on postnatal follow-up. Glomerular filtration rate was below normal range in 44.4%, 12.5% and 0% at <1 year, age 1 to 3 years and thereafter, respectively. Hyperfiltration was detected in 18.5% and 82.6% at <1 year and >3 years, respectively. Hypertension was documented in 35% at age 1 to 3 years but in none at an older age. Proteinuria was absent in all children. CONCLUSION: Congenital SFK is apparently associated with little or no renal damage in infancy or childhood. Compensatory enlargement of the functioning kidney begins in utero and might serve as a prognostic indicator for normal renal function after birth.

Diagnostic accuracy of midtrimester antenatal ultrasound for multicystic dysplastic kidneys.

OBJECTIVES: To establish the diagnostic accuracy of obstetric ultrasound at a tertiary fetal medicine center in the prenatal detection of unilateral and bilateral multicystic dysplastic kidney (MCDK) in fetuses in which this condition was suspected, and to undertake a systematic review of the relevant literature. METHODS: This was a retrospective observational study of all cases referred to a regional tertiary fetal medicine unit due to suspicion of either unilateral or bilateral MCDK between 1997 and 2015. Diagnosis was confirmed by postnatal ultrasound reports or postmortem examination. The accuracy of prenatal ultrasound in the diagnosis of MCDK was calculated. Using a systematic search strategy we also performed a review of the literature regarding the prenatal diagnosis and diagnostic accuracy of MCDK. RESULTS: We included 144 women in our analysis; 37 (25.7%) opted for pregnancy termination (TOP) (due to unilateral MCDK with additional abnormalities, suspected bilateral MCDK or severe obstructive uropathy). Complete pre- and postnatal data were available in 126 pregnancies, including 104 livebirths, 19 TOPs with postmortem findings available and three intrauterine fetal deaths. Two infants died shortly after birth (due to known bilateral MCDK or known cranial vault defect). The overall number of cases of MCDK confirmed postnatally was 100; of these, 98 were diagnosed prenatally (true positive), while two were thought to be hydronephrosis prenatally (false negative) and the diagnosis of MCDK was made after birth. In nine cases, the initial antenatal diagnosis of suspected MCDK was revised, either later in pregnancy (n = 2) or postnatally (n = 7) (false positive). Overall, the diagnostic accuracy in our population for the use of antenatal ultrasound to detect MCDK was 91.3%, while that reported in the existing literature was found to range from 53.3% to 100%. MCDK was isolated in the majority (71%) of cases, while in 29% of cases it was found to be associated with other renal and extrarenal fetal abnormalities. CONCLUSIONS: Antenatal ultrasound had a diagnostic accuracy of about 91% in the prediction of postnatal MCDK and can therefore be used to guide antenatal counseling. However, prenatal or postnatal revision of the diagnosis occurred in about 7% of cases and parents should be counseled appropriately. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Transcriptional dysregulation in the ureteric bud causes multicystic dysplastic kidney by branching morphogenesis defect.

PURPOSE: The calcineurin-NFAT signaling pathway regulates the transcription of genes important for development. It is impacted by various genetic and environmental factors. We investigated the potential role of NFAT induced transcriptional dysregulation in the pathogenesis of congenital abnormalities of the kidneys and urinary tract. MATERIALS AND METHODS: A murine model of conditional NFATc1 activation in the ureteric bud was generated and examined for histopathological changes. Metanephroi were also cultured in vitro to analyze branching morphogenesis in real time. RESULTS: NFATc1 activation led to defects resembling multicystic dysplastic kidney. These mutants showed severe disorganization of branching morphogenesis characterized by decreased ureteric bud branching and the disconnection of ureteric bud derivatives from the main collecting system. The orphan ureteric bud derivatives may have continued to induce nephrogenesis and likely contributed to the subsequent formation of blunt ended filtration units and cysts. The ureter also showed irregularities consistent with impaired epithelial-mesenchymal interaction. CONCLUSIONS: This study reveals the profound effects of NFAT signaling dysregulation on the ureteric bud and provides insight into the pathogenesis of multicystic dysplastic kidney. Our results suggest that the obstruction hypothesis and the bud theory may not be mutually exclusive to explain the pathogenesis of multicystic dysplastic kidney. Ureteric bud dysfunction such as that induced by NFAT activation can disrupt ureteric bud-metanephric mesenchyma interaction, causing primary defects in branching morphogenesis, subsequent dysplasia and cyst formation. Obstruction of the main collecting system can further enhance these defects, producing the pathological changes associated with multicystic dysplastic kidney.

The antenatally detected pelvi-ureteric junction stenosis: advances in renography and strategy of management.

This review includes an analysis of new developments in the field of renography, the predictive factors suggesting the need for pyeloplasty in cases of pelvi-utereric stenosis detected antenatally and integration of the pelvi-ureteric junction stenosis within the framework of antenatally detected hydronephrosis.

Compensatory enlargement of a solitary functioning kidney during fetal development.

OBJECTIVE: To determine the degree of compensatory enlargement, and its time of onset, of the solitary functioning kidney (SFK) in fetuses with unilateral renal agenesis (URA) or unilateral multicystic kidney dysplasia (MCKD). METHODS: This was a retrospective study of fetuses with URA or MCKD diagnosed prenatally and confirmed postnatally in the period from January 1999 to May 2011. Fetuses with any other congenital anomalies were excluded. Measurements of kidney length were retrieved from our prenatal ultrasound database and a nomogram was established and compared with that for normal kidney length. RESULTS: In total, 67 fetuses were identified, 60 with MCKD and seven with URA, for which we obtained 147 kidney length measurements from our database. Mean gestational age at time of measurement was 29.7 (range, 18.4-36.7) weeks. Compensatory enlargement, defined as renal length >95(th) percentile for gestational age, was demonstrated in 87% of the MCKD cases and 100% of the URA cases (88% of cases overall). We estimated the mean enlargement for an SFK (defined as difference from 50(th) percentile for normal renal length) at 36 weeks' gestation to be 23.1% (9.25 mm), with the mean value being 11.4% (5.04 mm) greater than the 95(th) percentile for a normal kidney at this gestational age. Compensatory enlargement of SFKs was evident from the 20(th) week of gestation onwards. CONCLUSION: Compensatory enlargement of SFKs occurs in almost 90% of fetuses with MCKD or URA, and may be observed from the 20(th) week of gestation onwards.

Unilateral anomalies of kidney development: why is left not right?

Abnormal renal development results in congenital anomalies of the kidney and urinary tract. As many studies suggest that renal malformations are more often found on the left side, a meta-analysis was performed on the distribution of five different unilateral anomalies: multicystic dysplastic kidney, renal agenesis/aplasia, renal ectopia, pelviureteral junction obstruction, and non-obstructive non-refluxing megaureter. Of these anomalies, the left side was affected in 53%, 57%, 56.9%, 63.2%, and 62.5% of patients, respectively, significantly different when compared with an anticipated 50% of left-sided anomalies. An exception to this left-side predominance was found in females with combined genital anomalies and unilateral renal agenesis that commonly present on the right side. The exact mechanisms leading to these lateralizations remain to be determined but may involve vascular development, differential gene expression, or susceptibility to environmental factors such as hypoxia. This remains largely speculative, however, illustrating our limited knowledge of embryogenesis in general and nephrogenesis in particular.

Morphological and functional analyses of two infants with obstructive renal dysplasia.

Renal dysplasia associated with urinary tract obstruction comprises two distinct phenotypes, i.e., multicystic dysplastic kidney (MCDK) and obstructive renal dysplasia (ORD). MCDK is a common manifestation in infants with renal dysplasia, which is characterized by multiloculated thin-walled cysts with no functional parenchyma and an atretic ureter owing to pyelocalyceal occlusion early in fetal life. In contrast, ORD is an extremely rare condition which is caused by severe obstruction of the distal ureter or urethra. Here, we report two infants with ORD. Both patients manifested unilateral kidney enlargement with multiple cortical cysts, mild hydronephrosis, and marked dilatation of the ipsilateral ureter. Contralateral kidneys and urinary tracts revealed no apparent radiological abnormalities. Serial ultrasonographic studies of fetal and neonatal kidneys in both cases revealed that ureteral dilatation was evident at gestational week 16 and 27, respectively, and most of the cortical cysts disappeared within 1-3 months after birth. The functions of the affected kidneys were severely impaired but evident at the time of birth. These manifestations were consistent with a diagnosis of ORD, and were distinct from the features of MCDK. Our observation of fetal and infantile kidneys in these two cases provides us with a better understanding of the pathogenesis of ORD.

Multicystic dysplastic kidney and cystic accessory uterine cavity: a new prenatally diagnosed association.

The co-existence of renal and mullerian anomalies is well-recognised. Multicystic dysplastic kidneys (MCDK) are known to be associated with the presence of genital cysts in both males and females, but this is the first report of a prenatally diagnosed MCDK associated with a non-communicating cystic uterine cavity. The management of these abnormalities in childhood is not well-established.

Molecular events involved in the morphogenesis of multicystic dysplastic kidney.

INTRODUCTION: Wnt-1 is capable of inducing metanephric mesenchyme to undergo tubulogenesis. A relationship between the degree of cystogenesis and reduced E-cadherin (E-cad) expression was described. Syndecan-1 (Sdc-1) has a critical role in kidney development. MATERIALS AND METHODS: Ten multicystic dysplastic kidneys (MCDKs) were stained with hematoxylin and eosin and immunohistochemistry was performed using Wnt-1, E-cad and Sdc-1 antibodies. Eight unaffected kidneys were used as controls. RESULTS: Strong Wnt-1 immunostaining occurred inside cystic/tubular epithelial cells and in blastematous foci. An immunoreaction was observed in glomerular epithelial cells. In controls, just weak cytoplasmic Wnt-1 positivity was seen in tubular epithelial cells. E-cad reaction was negative in MCDKs while strong immunostaining was common in tubular cells of controls. A strong Sdc-1 immunoreaction depicted cystic, tubular and glomerular epithelial cells in MCDKs while Sdc-1 expression documented weak positivity in tubular epithelium alone. CONCLUSIONS: Our data are in accordance with an involvement of Wnt-1 in normal nephrogenesis and with its role in altered epithelial differentiation of metanephric mesenchyme in MCDKs. Wnt-1 signal may function to suppress E-cad expression, a predisposing event for cystogenesis. High expression of Sdc-1 in tubular/cystic epithelial cells of MCDKs might alter the normal transition of stages of the developmental process and modify the anion charge of the glomerular barrier.

Bladder agenesis in a male neonate.

Bladder agenesis, especially in male, is a rare congenital anomaly. This is a case report of a male patient with several congenital anomalies including penoscrotal transposition, severe kidney's dysplasia, and agenesis of the bladder. The patient lived for 4 months and died because of severe pneumonia.

Antenatally diagnosed giant multicystic dysplastic kidney resected during the neonatal period.

At 24 weeks of gestation, a fetus was suspected of having a huge intraabdominal cyst by fetal ultrasound. Multicystic dysplastic kidney (MCDK) was the most probable diagnosis; however, because a solid area was visualized in the large cystic lesion, a neoplasm of the kidney could not be ruled out. A 3529-g boy was born at 35 weeks of gestation by cesarean delivery. Eight days after birth, the tumor was resected. Histopathologic examination confirmed MCDK. The cause of MCDK in this patient was assumed to be ureteral obstruction in early fetal life. These findings suggested that the affected kidney had experienced mesenchyme-to-epithelium transition followed by interaction between the metanephric blastema and ureteral bud.

Dysplastic kidneys.

Dysplastic kidneys are common malformations affecting up to 1 in 1000 of the general population. They are part of the spectrum of Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT) and an increasing number of children are being diagnosed on antenatal ultrasound. In the past, these patients may not have been detected until adulthood following investigation for other illness, or even as incidental findings at post mortem, unless there was severe bilateral dysplasia leading to Potter's sequence or renal failure in childhood. Excluding syndromic cases with defects in other organ systems, features linked to worse prognosis at presentation are: (1) bilateral disease; (2) decreased functional renal mass (which encompasses not just small kidneys but also large ones where cysts replace normal architecture); (3) lower urinary tract obstruction; and (4) anhydramnios or severe oligohydramnios. Dysplasia and renal function are dynamic and can evolve during pregnancy, so repeated assessment is necessary when pathology is expected. Worsening dimensions or decreasing amniotic fluid levels imply poorer prognosis, but there are no proven therapies during pregnancy, though vesicoamniotic shunting may be indicated with obstruction. Postnatal investigations aim to define the anatomy, which helps to estimate risks of infection and kidney function. Management might then involve observation, prophylactic antibiotics, surgery and/or renal support. Risks of renal malignancy and hypertension are low during childhood, but longer-term follow-up is needed, particularly to determine blood pressure and renal function in adulthood and pregnancy. Around 10% of cases have a family history of significant renal/urinary tract malformation. Monogenic causes include mutations in individual genes, such as TCF2/hepatocyte nuclear factor 1ss (HNF1beta), PAX2 and uroplakins, but there are also recent reports of children with compound heterozygote mutations in several renal/urinary tract developmental genes. Effective genetic screening in future may require gene chip or other techniques to assess multiple genes concurrently, but this should not replace a multidisciplinary approach to these often difficult cases.

Left-sided gastroschisis and bilateral multicystic dysplastic kidneys: a rare combination of anomalies.

Left-sided gastroschisis is very rare. We report a case of left-sided gastroschisis associated with bilateral multicystic dysplastic kidneys. This combination of anomalies is unknown. The pathogenesis of gastroschisis is not well understood. It is now viewed as a malformation rather than disruption. The findings in this case support this view. The combination of dysplastic kidneys with ventral body wall defect suggests an early developmental defect.

Embryology and genetics of primary vesico-ureteric reflux and associated renal dysplasia.

Congenital anomalies of the kidney and urinary tract, as well as primary vesico-ureteric reflux (VUR) and associated renal dysplasia, are the most relevant causes of end-stage renal failure in the pediatric population. In vivo and in vitro experimental studies have allowed the identification of several genes involved both in ureteric bud branching, ureteric elongation and insertion into the bladder, and in nephrogenesis. It has been proposed that both renal and ureteral abnormalities, as well as the associated renal hypo-dysplasia, may derive from a common mechanism as the result of a dysregulation of the normal developmental program. The large homologies between mice and the human genome suggest that the same genes could be involved both in rodent and human VUR. Furthermore, epidemiological observations suggest that not only syndromic but also isolated VUR is an inherited trait. Linkage analysis for homologous mouse genes in humans, genome-wide linkage studies in multigenerational families and association studies by polymorphisms support the hypothesis that VUR is genetically heterogeneous and is caused by a number of different genes acting with random environmental effects. The present teaching paper is an overview of the embryology and genetics of primary VUR and associated congenital reflux nephropathy.

Histomorphology of renal dysplasia--an autopsy study.

A retrospective analysis of pediatric autopsies in the past 18 years was done with the aim of studying the histomorphology of renal dysplasia. Renal dysplasia comprised 150 (3.66%) of the 4,099 pediatric autopsies from 20 weeks of gestation to 1 year of life. Primitive ducts with the fibromuscular collar, the sine qua non of renal dysplasia, was seen in all cases. Lobar disorganization and cysts were seen in all cases except for the 7 cases of hypodysplasia. Other elements were seen in varying proportions: cartilage in 33.7%, bone in 1.08%, thickening of basement membrane of the primitive ducts in 64.13%, extramedullary hematopoiesis in 98.9%, nerve twigs in 72.8%, and nodular renal blastema in 2.17% cases. In unilateral multicystic dysplasia/renal agenesis, the contralateral kidney showed abnormalities in 44.45% and 47.37% of cases, respectively.

Meckel-Gruber syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis.

This article provides an overview of the major pathologic manifestations of Meckel-Gruber syndrome, current knowledge about its pathogenesis, minimal diagnostic criteria, and differential diagnosis. Typical sonographic findings (occipital encephalocele, postaxial polydactyly, and cystic enlargement of the kidneys) allow for diagnosis of most cases before the 14th week of gestation, but the pathologist may encounter clinically unsuspected or atypical cases that require morphologic confirmation. In these cases, a meticulous autopsy is necessary to establish the diagnosis of Meckel-Gruber syndrome.

Multicystic dysplastic kidney and pelviureteric junction obstruction.

Two infants with nonfunctioning antenatally detected multicystic dysplastic kidneys developed acute renal failure in conjunction with pelviureteric obstruction of the contralateral kidney at 9 and 14 months of age, respectively. The initial postnatal ultrasounds had shown mild pelvic dilatation in both cases. Clinicians need to be aware of the possibility of late obstruction. We suggest that it is good practice to review patients with antenatally detected urinary tract abnormalities and equivocal investigations at joint nephrouroradiology meetings.