Distal ureteral atresia – an embryological dilemma

Introduction: Distal ureteral atresia is a rare urinary tract anomaly generally associated with ipsilateral renal dysplasia and abnormalities such as multicystic dysplastic kidney, hydronephrosis and megaureter in the contralateral kidney. Despite burgeoning investigation modalities, definitive preoperative diagnosis of this condition is rarely feasible, also the embryological disarray of events that result in the development of this anomaly and the associated malformations is not clearly understood. Case presentation: We hereby report two cases of distal ureteral atresia and discuss the diversity in their presentations, diagnosis, atypical associations and management and review the possible embryological mal-development. Conclusion: Distal ureteral atresia with urogenital sinus as in Case 1 has not been documented so far and a plausible embryological explanation is deduced regarding its occurrence. The course of the affected kidney following timely and adequate relief of obstruction in Case 2 is depicted, highlighting the eventual management. Level of evidence: Not applicable

Dialysis Access-Associated Steal Syndrome with Percutaneous Endovascular Arteriovenous Fistula Creation.

Background: Dialysis access-associated steal syndrome is an infrequent complication after hemodialysis access creation. Clinical symptoms depend on the degree of steal. Mild symptoms include coldness, numbness and pain during dialysis. Severe steal can present with rest pain, cyanosis and ulcerations, and may require surgical ligation of the fistula. With recent advances in arteriovenous fistula creation, percutaneous endovascular arteriovenous fistula creation has demonstrated better maturation and patency rates with lower risk of wound healing and infection rates as compared to surgically created hemodialysis access. Percutaneous creation offers a minimally invasive alternative, though complications have been reported. The following presents the first described case of DASS following the use of percutaneous endovascular arteriovenous fistula creation, and discusses risk factors and management. Case Presentation: Our case is that of a 27-year-old male with end stage renal disease due to congenital renal dysplasia, who underwent left percutaneous arteriovenous fistula creation for initiation of dialysis. Two months after the procedure the patient complained of coldness, pain, tingling, and numbness in the left arm during dialysis, concerning for steal syndrome. The patient subsequently underwent brachial artery angiogram, which showed predominant flow through the fistula and minimal antegrade flow through the ulnar and interosseous arteries towards the hand, with a focal, severe stenosis in the distal ulnar artery. Angioplasty of the stenosis was performed, though steal symptoms continued. Conclusions: DASS, though rare, can be seen with percutaneous arteriovenous fistula creation. Identification of the risk factors prior to creation, especially in patients who are at higher risk of peripheral vascular disease, can help avoid this complication. Management is largely guided by clinical presentation. As long as there is adequate collateral supply to the extremity, single vessel occlusion is not a contraindication to percutaneous arteriovenous fistula creation with the use of WavelinQ technology. Careful patient selection with pre-creation angiogram may reduce the risk of symptomatic steal.

A case report of Potter’s syndrome in a newborn

Introduction. Potter’s sequence is a very rare and severe syndromic complex that includes congenital kidney defects leading to oligohydramnios, lung hypoplasia and structural skeletal disorders. Clinical case presentation: observation of a boy born from the 5th pregnancy to the mother at 37 weeks. Antenatally, the fetus was found to have bilateral renal and urinary bladder agenesis, malformations of the limbs, but the parents refused to terminate the pregnancy. After birth, the child was diagnosed with Potter’s syndrome with severe hypoplasia of the lungs, which required mechanical ventilation. In 2 hours after birth, the child developed a tension pneumothorax, which was arrested by performing drainage of the pleural cavity. During the day, the patient received complex treatment in the intensive care unit, despite which, by the 2nd day of life, the death of the child occurred. Currently, there are no guidelines for the treatment of Potter syndrome with proven positive long-term outcomes.Discussion. Children with Potter syndrome do not have the same set of symptoms, but they develop a chain of events leading to a common ultimate result - decreased amount of amniotic fluid. Abnormalities leading to oligohydramnios may include severe hypoplasia, dysplasia, polycystic, obstructive uropathy or renal agenesis. In most cases, the disease occurs sporadically, but there are also forms with transmission of the disorder through successive generations: autosomal dominant or recessive inheritance of polycystic disease, hereditary renal dysplasia caused by mutations in RET, UPK3A genes and other chromosomal abnormalities.Conclusion. Potter syndrome is a set of severe syndromes manifested by abnormalities in the development of kidneys, oligohydramnios, leading to lung hypoplasia, skeletal disorders and other congenital anomalies. The severity of congenital defects included in the set depends on the time periods when oligohydramnios occurred. Despite the availability of experimental therapies, the disease is now considered to be fatal.

Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept

Renal dysplasia is a severe congenital abnormality of the kidney parenchyma, which is an important cause of end-stage renal failure in childhood and early adulthood. The diagnosis of renal dysplasia relies on prenatal or postnatal ultrasounds as children show no specific clinical symptoms before chronic kidney disease develops. Prompt diagnosis is important in terms of early introduction of nephroprotection therapy and improved long-term prognosis. Metabolomics was applied to study children with renal dysplasia to provide insight into the changes in biochemical pathways underlying its pathology and in search of early indicators for facilitated diagnosis. The studied cohort consisted of 72 children, 39 with dysplastic kidneys and 33 healthy controls. All subjects underwent comprehensive urine metabolic profiling with the use of gas chromatography and liquid chromatography coupled to mass spectrometry, with two complementary separation modes of the latter. Univariate and multivariate statistical calculations identified a total of nineteen metabolites, differentiating the compared cohorts, independent of their estimated glomerular filtration rate. Seven acylcarnitines, xanthine, and glutamine were downregulated in the urine of renal dysplasia patients. Conversely, renal dysplasia was associated with higher urinary levels of dimethylguanosine, threonic acid or glyceric acid. This is the first metabolomic study of subjects with renal dysplasia. The authors define a characteristic urine metabolic signature in children with dysplastic kidneys, irrespective of renal function, linking the condition with altered fatty acid oxidation, amino acid and purine metabolisms.

Early Renal Ultrasound in Congenital Solitary Kidney May Help to Select Patients at Lower Risk of Associated Vesicoureteral Reflux

<b><i>Background:</i></b> Vesicoureteral reflux (VUR) may be associated with renal dysplasia and reduced renal length (RL). The diagnosis of VUR in children with congenital solitary functioning kidney (CSFK) identifies patients at risk of kidney injury but exposes to invasive procedures. <b><i>Objective:</i></b> We aimed to test the hypothesis that an RL &#x3e;2 standard deviation score (SDS) in the first months of life – reflecting renal hyperplasia – could identify CSFK patients with lower probability of presenting VUR. <b><i>Method:</i></b> We retrospectively selected 207 CSFK patients with prenatal diagnosis of CSFK and having undergone renal ultrasound (RUS) both at 0–3 and 10–13 months of life, renal scintigraphy, and cystourethrography/cysto­scintigraphy. We compared the cumulative proportion of an RL &#x3e;2 SDS by Kaplan-Meier analysis and evaluated the odds to present VUR of patients with an RL &#x3e;2 SDS both at the first and second RUS. <b><i>Results:</i></b> Overall, 3.3% of patients with VUR and 22.0% of patients without VUR presented an RL &#x3e;2 SDS at the first RUS (<i>p</i> = 0.02). At the second RUS, 53.3% of patients with VUR and 52.5% of patients without VUR presented an RL &#x3e;2 SDS (<i>p</i> = 0.93). Patients without VUR presented higher cumulative proportion of an RL &#x3e;2 SDS at 3 months of life than those with VUR (<i>p</i> = 0.02). This difference however disappeared at 11 and 13 months of age (<i>p</i> = 0.17 and <i>p</i> = 0.54, respectively). An RL &#x3e;2 SDS within 3 months of life presented an OR for VUR of 0.12 (95% CI: 0.02–0.92; <i>p</i> = 0.005), while an RL &#x3e;2 SDS at 12 months of life presented an OR for VUR of 0.96 (95% CI: 0.45–2.1; <i>p</i> = 0.93). <b><i>Conclusion:</i></b> Only an RUS made in the first months of life could identify CSFK patients at lower risk of presenting an associated VUR.

Elevated sweat chloride test: is it always cystic fibrosis?

Background The sweat chloride test (ST) is the gold standard for cystic fibrosis (CF) diagnosis in symptomatic patients, within the newborn screening and in the follow-up of CF patients during molecular therapies. However, false positives have been reported in patients with different diseases. We describe and discuss 4 cases due to different clinical conditions in which we recorded false positive ST, and the test remained altered for a period of varying length. Cases presentation Case 1: Eight months old female child suffering from constipation, recurrent vomiting and failure to thrive, family history of recurrent pancreatitis without mutations in the PRSS1 and SPINK1 genes. Both ST and fecal elastase were altered although no CFTR gene mutations were found. Due to rapid clinical deterioration, celiac disease was suspected and diagnosed by laboratory tests and intestinal biopsy. After 2 weeks of gluten-free diet ST and fecal elastase normalized. Case 2: 14 months old male suffering from bilateral renal dysplasia, episodes of metabolic alkalosis, recurrent respiratory infections and recurrent vomiting. The child had more ST positives, but no CFTR mutations were found. During follow-up, he developed sensorineural hearing loss and an atrial septic defect was found. Finally, a diagnosis of Klinefelter was made, but the ST normalized several years later. Case 3 and 4: Two boys with stubborn constipation and fecal occlusion treated with Poly Ethylene Glycol (PEG) with salts showed pathological ST. The test returned normal a few days after stopping treatment. Conclusions We hypotesized the possible causes of ST alteration in these conditions: in celiac disease it could be due to a transient dysregulation of the aquaporins, rapidly reversed by the diet; in Klinefelter, it may be due to stable pubertal hypoandrogenism; while, the PEG formulation itself contains salts that can temporarily alter ST.

A Novel GATA3 Variant Causing Familial Hypoparathyroidism, Renal Agenesis and Sensorineural Deafness Presenting With Atypical Symptoms of Chronic Hypocalcaemia

Introduction: Familial hypoparathyroidism is a rare cause of hypocalcaemia. We report a case of long-standing hypocalcaemia secondary to hypoparathyroidism caused by a novel GATA3 variant resulting in multiple organ involvement. Case: A 20 year old girl was referred to our bone metabolic clinic for hypocalcaemia. Her past medical history included Bechet’s disease, epilepsy and depression. She had bilateral sensorineural hearing loss and encephalitis as a child. She underwent right nephrectomy for an atrophic non-functioning kidney at the age of 16. Current medication included hydroxychloroquine, diazepam, oral calcium and cholecalciferol. It was noted that the hypocalcaemia dated back to 8 years, she denied any typical symptoms of hypocalcaemia but she did report visual and auditory hallucinations, fatigue and had low seizure threshold. She sustained recurrent fractures of her arm, elbow and wrist. Initial investigations: Corrected calcium 1.88 (2.20-2.60mmol/L), Phosphate 1.54 (0.80–1.50mmol/L), PTH 1.2 (1.6–6.9pmol/), 25-OH vitamin D 37 (50-120nmol/L). Myeloma screen, thyroid, renal and liver functions were all within the normal reference range. Other bone markers: Serum Procollagen Type 1 Amino Terminal Peptide was mildly raised at 82 (19-69ug/L), CTX 0.42 (0.1-0.5ug/L), 1,25 OH Vitamin D 29 (55-139pmol/L), 24,25-dihydroxyvitamin D was normal with normal 25:24,25 Dihyroxyvitamin D ratio at 18 normal. Bone density was in the normal range for her age. MRI of the brain was normal with no evidence of calcification. There was a family history of hypocalcemia in her estranged father. Subsequent genetic analysis showed a novel likely pathogenic GATA3 missense variant (c.961T&gt;C p.(Cys321Arg). She was started on alfacalcidol and achieved near normocalcemia with adjusted calcium levels of 2.18nmol/L. Conclusion: Pathogenic variants in the GATA3 gene are responsible for Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome. In our patient, a novel missense variant in GATA3, p.(Cys321Arg), has been detected. This variant disrupts one of four conserved cysteine residues within a zinc-finger domain, which is involved in DNA binding and is presumed to have a deleterious effect on protein function. Patients may have longstanding asymptomatic hypocalcaemia with atypical features hence genetic testing is recommended in patient with multi-organ involvement. Alfacalcidol successfully restored calcium homeostasis in this case.