Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract

Harris, Meredith; Schuh, Meredith P.; McKinney, David; Kaufman, Kenneth M.; Erkan, Elif

doi:10.3389/fped.2022.898773

Cited by 3 publications

(2 citation statements)

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“…Multicystic dysplastic kidney (MCDK) disorder was traditionally assumed to be a developmental anomaly in which the renal parenchyma fails to develop, leading to the presence of primitive ducts, cysts, and, potentially, tissues of extrarenal origin [12,13]. However, the research conducted by Harris et al suggests that MCDK, in its severe form, can be classified as part of the broader spectrum of ciliopathies, requiring further research to comprehend its underlying molecular mechanisms [14].…”

Section: Cystic Kidney Disease As Part Of the Ciliopathies Spectrummentioning

confidence: 99%

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Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review

Grlić,

Gregurović,

Martinić

et al. 2024

Children

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Introduction: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. Aim: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period. Methods and Materials: Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes. Results: During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet–Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0–31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0–141.0) months. The median follow-up duration in the cohort was 3.0 (1.0–7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation. Conclusion: This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.

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Section: Cystic Kidney Disease As Part Of the Ciliopathies Spectrummentioning

confidence: 99%

“…Children 2024, 11, 392 3 of 27 extrarenal origin [12,13]. However, the research conducted by Harris et al suggests that MCDK, in its severe form, can be classified as part of the broader spectrum of ciliopathies, requiring further research to comprehend its underlying molecular mechanisms [14].…”

Section: Cystic Kidney Disease As Part Of the Ciliopathies Spectrummentioning

confidence: 99%

Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review

Grlić,

Gregurović,

Martinić

et al. 2024

Children

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Genetic Spectrum of Congenital Anomalies of the Kidney and Urinary Tract in Chinese Newborn Genome Project

Huang¹,

Shen²,

Wu³

et al. 2023

Kidney International Reports

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Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance

Diniz,

Ngo,

Colon-Leyva

et al. 2023

Nat Commun

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Nephron endowment at birth impacts long-term renal and cardiovascular health, and it is contingent on the nephron progenitor cell (NPC) pool. Glycolysis modulation is essential for determining NPC fate, but the underlying mechanism is unclear. Combining RNA sequencing and quantitative proteomics we identify 267 genes commonly targeted by Wnt activation or glycolysis inhibition in NPCs. Several of the impacted pathways converge at Acetyl-CoA, a co-product of glucose metabolism. Notably, glycolysis inhibition downregulates key genes of the Mevalonate/cholesterol pathway and stimulates NPC differentiation. Sodium acetate supplementation rescues glycolysis inhibition effects and favors NPC maintenance without hindering nephrogenesis. Six2Cre-mediated removal of ATP-citrate lyase (Acly), an enzyme that converts citrate to acetyl-CoA, leads to NPC pool depletion, glomeruli count reduction, and increases Wnt4 expression at birth. Sodium acetate supplementation counters the effects of Acly deletion on cap-mesenchyme. Our findings show a pivotal role of acetyl-CoA metabolism in kidney development and uncover new avenues for manipulating nephrogenesis and preventing adult kidney disease.

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Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract

Cited by 3 publications

References 58 publications

Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review

Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review

Genetic Spectrum of Congenital Anomalies of the Kidney and Urinary Tract in Chinese Newborn Genome Project

Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance

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