Bilateral Renal Abnormalities Research Articles

Ultrasound of the Siren Syndrome (Sirenomelia) in the District of Bamako Apropos of a Case

Sirenomelia is a rare fetal malformation with more or less complete fusion of both lower limbs consistently associated with bilateral renal abnormalities. The positive diagnosis can be made antenatally by ultrasound during the first trimester of pregnancy but often before the 22 weeks of amenorrhea. The objective was to think about the possible diagnosis by ultrasound in front of the urinary anomalies and the ologiamnios during the morphological study of the second trimester of pregnancy. We report a case of sirenomelia in a 25-year-old lady as part of the routine prenatal assessment suspected and confirmed during the morphological ultrasound of the second trimester of pregnancy and confirmed after the termination of pregnancy in Mali in the Health Center of Reference of commune III of the district of Bamako. The morphological ultrasound made it possible to diagnose the malformation of the urinary tract, the amniotic fluid and to make the therapeutic decision of medical termination of pregnancy at the end of confirming the siren syndrome.

Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole-exome sequencing.

BackgroundIn prenatal care, accumulating evidences has demonstrated that whole‐exome sequencing (WES) expedites the genetic diagnosis of fetal structural anomalies. However, the clinical value of WES in the diagnosis of prenatal isolated congenital anomalies of the kidney and urinary tract (CAKUT) is unknown.MethodsForty‐one fetuses with unexplained isolated CAKUT, normal karyotype and negative chromosomal microarray analysis (CMA) results, underwent WES and were accordingly grouped as (a) Group 1: complex cases with bilateral renal abnormalities (N = 19); and (b) Group 2: cases with isolated unilateral fetal renal abnormalities (N = 22).ResultsThe detection rate of WES for pathogenic variants and incidental variants was 7.32% (3/41) and 2.4% (1/41), respectively. The three pathogenic variants were identified in the genes ACTA2 (multisystem smooth muscle dysfunction syndrome), PKHD1 (autosomal recessive form of polycystic kidney disease), and PKD1 (autosomal dominant polycystic kidney disease type 1). The incidental variants were detected in genes PPM1D (syndromic neurodevelopmental disorders). Furthermore, all above fetuses carrying pathogenic variants came from bilateral kidney anomalies. Thus, the detection rate was 0 for fetuses with unilateral fetal renal abnormalities and 15.7% (3/19) for bilateral renal abnormalities.ConclusionThis cohort shows that prenatal WES is a supplementary approach for the etiologic diagnosis of unexplained isolated CAKUT with negative CMA, especially for fetuses with bilateral renal abnormality.

Genotype and Phenotype Analyses in Pediatric Patients with HNF1B Mutations.

HNF1B mutations, one of the most common causes of congenital anomalies of the kidney and urinary tract, manifest as various renal and extrarenal phenotypes. We analyzed the genotype-phenotype correlations in 14 pediatric patients with HNF1B mutations. Genetic studies revealed total gene deletion in six patients (43%). All patients had bilateral renal abnormalities, primarily multiple renal cysts. Twelve patients exhibited progressive renal functional deterioration, and six of them progressed to kidney failure. The annual reduction in estimated glomerular filtration rate was−2.1 mL/min/1.73 m2. Diabetes developed in five patients (36%), including one patient with new-onset diabetes after transplantation. Neurological deficits were noted in three patients (21%), one with total gene deletion and two with missense mutations. Pancreatic abnormalities were more frequent in patients with missense mutations than in patients with other types of mutations. Genotype showed no significant correlation with renal outcomes or other extrarenal manifestations. The HNF1B scores at the times of onset and genetic diagnosis were <8 in two patients and one patient, respectively. Diagnosis of HNF1B mutations is clinically difficult because of extreme phenotypic variability and incomplete penetrance. Furthermore, some phenotypes develop with age. Therefore, patient age should be taken into consideration to increase the diagnostic rate, because some phenotypes develop with age.

Markers of Chronic Kidney Disease in Children with Obstructive Uropathy or Vesicoureteral Reflux

Background. Identification of markers of chronic kidney disease and its progression in the early stages of the disease is important, however, the most of research concerns late (3–5) stages of the disease. Objective . Identification of the markers of chronic kidney disease (CKD) and its progression in the early stages of the disease in children with obstructive uropathy and vesicoureteral reflux. Methods. Prospective follow-up (for 5 years) of 92 children with obstructive and reflux uropathies (1st to 4th stages of CKD). All patients had episodes of urinary tract infections, mostly pyelonephritis, minimum once a year. Results . High prevalence of proteinuria (60.9%), reduced renal functional reserve (88.7%) and disorders of cortical renal blood flow (by Doppler Color Flow Imaging) (69.6%) were found in children with 1st stage of CKD. Groups of children with proteinuria and a reduced renal functional reserve had a higher level of systolic and diastolic blood pressure in comparison with the patients without proteinuria and the reduced renal functional reserve (p < 0.05). In patients with 2–4 stages of CKD the glomerular filtration rate (GFR) correlated with atypical flora in the etiology of urinary tract infections (rpb = 0.66; n = 23; p = 0.0006), sex (boys had lower levels of GFR, rpb = 0.61; n = 23; p = 0.001), bilateral renal abnormalities (rpb = -0.53; n = 23; p = 0.009) the level of hemoglobin (r = 0.45; n = 23; p = 0.02). Conclusion . Markers of CKD of children with obstructive and reflux uropathies are: proteinuria, arterial hypertension, reduction of renal functional reserve and the impaired cortical renal blood flow (by Doppler Color Flow Imaging). The importance of arterial hypertension and proteinuria as markers of the progression of CKD of children with urinary tract obstruction and vesicoureteral reflux was confirmed. Additional markers for the progression of CKD in children with obstructive and reflux uropaties might be: male sex, bilateral renal abnormalities, anemia and atypical bacteriuria during relapses of urinary tract infections.

O-182 Hnf1b Mutations In Patients With Congenital Abnormalities Of Kidney And Urinary Tract (cakut): Are We Screening Too Much?

Background and aims Hepatocyte nuclear factor 1 beta (HNF1B) is involved in the development of kidneys, liver, pancreas and urogenital tract. Disorders have an extremely high heterogeneity in phenotype. We aim to define accurate criteria for screening in a prospective cohort of patients. Methods Based on the phenotypic characteristics described in literature, we defined major, minor and extra-renal selection criteria. Major criteria were defined as fetal bilateral hyperechogenic kidneys; multicystic dysplastic kidney or renal agenesis; hypoplastic or dysplastic kidneys or cysts from unknown origin. Minor criteria were defined as ectopic kidney; vesico-ureteral reflux; hydronephrosis and extrarenal criteria as diabetes; hypomagnesemia; hyperuricemia; hypokalemia; liver function abnormalities or positive familial history. We included all patients from our paediatric and adult nephrology department from January 2010 till April 2013 presenting with at least one major or one minor criterion with extra-renal manifestations in the personal or familial history. Results We screened a prospective cohort of 252 patients fitting the criteria mentioned above and detected HNF1B mutations in 10% (n = 20), with a complete deletion being the most common (n = 10), besides duplication or sequence abnormalities. In our cohort the best predictors for finding HNF1B mutations were bilateral renal abnormalities (p Conclusions Based on a prospective single centre cohort, we demonstrated that HNF1B-mutations are responsible for approximately 10% of CAKUT cases. Nonetheless, bilateral renal anomalies or cysts from unknown origin were the best predictors. These criteria might be useful for a more restricted screening protocol, but should be reaffirmed in a larger multicenter cohort.

Epidemiology of antenatally diagnosed isolated bilateral renal disease: a population study (NorCAS) in North East England, 1989-2009: Abstract P13 Table 1

Aims Antenatal diagnosis of bilateral renal disease can result in an infant born with renal or pulmonary failure. We interrogated Northern Congenital Abnormality Survey (NorCAS) database to answer following questions: What decisions did parents make based on this diagnosis? What were the outcomes of liveborn infants? How accurate were the antenatal diagnoses compared to post-natal findings in survivors? Methods The NorCAS register records all antenatally diagnosed fetal anomalies in a relatively stable population of 3.2 million with an annual birth rate of appropriately 35,000/year. We extracted all cases registered with isolated bilateral renal disease. Additional follow up data was obtained from the regional paediatric nephrology unit. Results In 20 years, 210 cases of isolated bilateral renal disease were identified antenatally. They were classified by the obstetricians into different diagnoses (table 1). Elective termination of pregnancy was undertaken in 110 (52%) fetuses. Of 91 born alive, 49 (54%) were alive at one year. Termination and survival rates differ between the groups with BRA and bMCKD being universally fatal. Concordance with postnatal findings ranged from 54%-88%. Conclusion This unique population based study highlights significant discrepancies between antenatal ultrasound diagnoses and postnatal findings in those born alive. In the last 20 years, significant number of fetuses with isolated bilateral renal abnormalities were terminated. Improved diagnostic tools are greatly needed to guide families make these very difficult decisions.

Ultrasound evaluation of prognosis in fetuses with posterior urethral valves

Purpose The aim of this study was to evaluate the ability of prenatal ultrasound markers to predict postnatal renal prognosis in fetuses with posterior urethral valves. Methods Medical files on fetuses with prenatal diagnosis of posterior urethral valves from 2000 to 2006 were reviewed retrospectively. Data from prenatal follow-up included gestational age at diagnosis, ultrasound renal parenchyma evaluation, and presence and time of oligohydramnios onset. Prenatal parameters studied were correlated to postnatal renal function. Results Thirty-one male fetuses were included. Six pregnancies were terminated. Of the remaining 25 pregnancies that were continued, 4 children had abnormal creatine and 21 normal creatinine levels at follow-up. Presence and time of oligohydramnios onset did not differ between groups ( P = .43). Ultrasound detected bilateral renal abnormalities in 3 fetuses (75%) with altered renal function, and 10 fetuses (55%) with normal creatinine, at follow-up. Conclusions None of the ultrasound parameters evaluated were able to reliably predict postnatal renal function.

A Phenotypic Variant of Knobloch Syndrome

Knobloch syndrome (KNO) is a rare autosomal recessive condition caused by pathogenic mutations in the COL18A1 gene. It is characterized by high myopia, vitreoretinal degeneration, retinal detachment and midline encephalocoele or midline occipital bone defect. We report a case of KNO confirmed by direct sequence analysis of the COL18A1 gene with typical ocular features, and previously unreported systemic features: occipital hair tuft with transient CSF leak and bilateral renal abnormalities. This case illustrates a new phenotypic variant of this syndrome.

Posterior Urethral Valves: Prenatal Diagnostic Signs and Outcome

Introduction: Urethral valves can be of enormous clinical importance. Both the prognosis for an affected fetus and the indication for a prenatal therapeutic intervention depend to a high degree on the accuracy of the prenatal diagnosis. Patients and Methods: The sonographic findings and the results of the postnatal diagnostic workup of 24 boys treated for urethral valves in our institute are analyzed in the present paper. Results: Out of a group of 900 children, diagnosed prenatally as having urinary tract anomalies, the postnatal diagnostic workup revealed 24 boys suffering from posterior urethral valves. The combination of megacystis, oligohydramnios, and bilateral renal abnormalities was present in 3 boys, and it was only in these cases that urethral valves were correctly identified as the underlying pathology. The largest group (n = 16) of these fetuses presented with bilateral hydronephrosis with and without megaureter. Megacystis in any combination with other findings was detected only in 4 patients. Oligohydramnios as a sign of impaired renal function was observed in four pregnancies. Four children suffered postnatally from beginning renal insufficiency. Eight infants (33%) required some form of respiratory support. This group included the 4 newborns with oligohydramnios during the pregnancy. Conclusions: Posterior urethral valves represent a rare but severe congenital malformation. They can disrupt the development of the entire urinary tract and may be life-limiting to the affected boy. Only rarely, however, are they manifested as the complete pathological picture on prenatal ultrasound. In most cases, bilateral impairment of the fetal renal development suggests severe subvesical obstruction. Thus in cases with bilateral renal impairment on prenatal ultrasonography, posterior urethral valves are to be excluded postnatally. Oligohydramnios is a predictor of a poor outcome of the renal function.

The relationship between early renal status, and the resolution of vesico-ureteric reflux and bladder function at 16 months.

To examine, in infants presenting with vesico-ureteric reflux (VUR), the relationship between the presence of initial renal abnormalities with the outcome of VUR and bladder function at 16 months of age. The study group comprised 40 infants (32 boys) presenting consecutively (29 after prenatal detection) with VUR grade III or greater (bilateral in 29) on the initial micturating cystogram (median age 8 weeks). The initial presence of abnormal kidneys was determined from isotopic renography and/or ultrasonography. These data were correlated with the outcome of VUR, from direct isotope cystography, and bladder function assessed by natural filling urodynamics, examined at age 16 months (mean 16.4 months, SD 2.1). Three groups were identified. Group 1 (eight boys and six girls) had normal kidneys bilaterally; initially grade III VUR was common. At 16 months bladder function was normal in 10 children and none had VUR (complete resolution). Group 2 (14 boys and two girls) had unilateral renal abnormalities; initially VUR was predominantly grade IV or grade V. At 16 months bladder function was normal in eight children and VUR resolved in eight, five of these with normal bladder function. Group 3 (10 boys) had bilateral renal abnormalities. Initially grade V VUR predominated; at 16 months the bladder function was normal in only one, and in the rest the emptying dynamics were abnormal. All 10 boys had persisting VUR (no resolution). In infants with moderate or severe VUR, resolution at 16 months old is associated with normal kidneys in a similar proportion of boys and girls. Resolution also correlates well with normal bladder function. Presentation in infancy with bilateral abnormal kidneys, associated with severe VUR in boys, is a poor prognostic sign for the early outcome of VUR and for bladder function.

Severe bilateral renal disease: correlation of antenatal and autopsy findings.

We report 20 infants with severe bilateral renal disease examined by prenatal ultrasound and by autopsy. In 17, the prenatal and pathologic diagnoses correlated well. Although the prenatal and autopsy findings differed in the three remaining cases, the autopsy confirmed the presence of severe bilateral renal abnormalities. All 20 pregnancies were complicated by oligohydramnios, which was severe in 60 per cent. Most of these fetuses had malformation of other organ systems. This series supports the utility of prenatal ultrasound examinations, but emphasizes the need for postnatal evaluation of congenital renal disease including pathologic examination of tissue when possible for correct classification and genetic counselling.