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A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney.

ABSTRACT: Congenital solitary functioning kidney (CSFK) is a birth defect that occurs in 1:1500 children and predisposes them to kidney injury. Its aetiology is likely multifactorial. In addition to known monogenic causes and environmental risk factors, common genetic variation may contribute to susceptibility to CSFK. We performed a genome-wide association study among 452 patients with CSFK and two control groups of 669 healthy children and 5363 unaffected adults. Variants in two loci reached the genome-wide significance threshold of 5 × 10^-8, and variants in 30 loci reached the suggestive significance threshold of 1 × 10^-5. Of these, an identified locus with lead single nucleotide variant (SNV) rs140804918 (odds ratio 3.1, p-value = 1.4 × 10^-8) on chromosome 7 was most promising due to its close proximity to HGF, a gene known to be involved in kidney development. Based on their known molecular functions, both KCTD20 and STK38 could explain the suggestive significant association with lead SNV rs148413365 on chromosome 6. Our findings need replication in an independent cohort of CSFK patients before they can be established definitively. However, our analysis suggests that common variants play a role in CSFK aetiology. Future research could enhance our understanding of the molecular mechanisms involved.

SUBMITTER: Groen In 't Woud S

PROVIDER: S-EPMC9775328 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney.

Groen In 't Woud Sander S Maj Carlo C Renkema Kirsten Y KY Westland Rik R Galesloot Tessel T van Rooij Iris A L M IALM Vermeulen Sita H SH Feitz Wout F J WFJ Roeleveld Nel N Schreuder Michiel F MF van der Zanden Loes F M LFM

Biomedicines 20221123 12

Congenital solitary functioning kidney (CSFK) is a birth defect that occurs in 1:1500 children and predisposes them to kidney injury. Its aetiology is likely multifactorial. In addition to known monogenic causes and environmental risk factors, common genetic variation may contribute to susceptibility to CSFK. We performed a genome-wide association study among 452 patients with CSFK and two control groups of 669 healthy children and 5363 unaffected adults. Variants in two loci reached the genome- ...[more]

PMID: 36551779

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Project description:ContextA congenital solitary functioning kidney (cSFK) is a common developmental defect that predisposes to hypertension and chronic kidney disease (CKD) as a consequence of hyperfiltration. Every urologist takes care of patients with a cSFK, since some will need lifelong urological care or will come with clinical problems or questions to an adult urologist later in life.ObjectiveWe aim to provide clear recommendations for the initial clinical management and follow-up of children with a cSFK.Evidence acquisitionPubMed and EMBASE were searched to identify relevant publications, which were combined with guidelines on related topics and expert opinion.Evidence synthesisInitially, cSFK diagnosis should be confirmed and risk factors for kidney injury should be identified using ultrasound. Although more research into early predictors of kidney injury is needed, additional congenital anomalies of the kidney or urinary tract and absence of compensatory kidney hypertrophy have repeatedly been associated with a worse prognosis. The role of voiding cystourethrography and antibiotic prophylaxis remains controversial, and is complicated by the exclusion of children with a cSFK from studies. A yearly follow-up for signs of kidney injury is recommended for children with a cSFK. As masked hypertension is prevalent, annual ambulatory blood pressure measurement should be considered. During puberty, an increasing incidence of kidney injury is seen, indicating that long-term follow-up is necessary. If signs of kidney injury are present, angiotensin converting enzyme inhibitors are the first-line drugs of choice.ConclusionsThis overview points to the urological and medical clinical aspects and long-term care guidance for children with a cSFK, who are at risk of hypertension and CKD. Monitoring for signs of kidney injury is therefore recommended throughout life. Large, prospective studies with long-term follow-up of clearly defined cohorts are still needed to facilitate more risk-based and individualized clinical management.Patient summaryMany children are born with only one functioning kidney, which could lead to kidney injury later in life. Therefore, a kidney ultrasound is made soon after birth, and other investigations may be needed as well. Urologists taking care of patients with a solitary functioning kidney should realize the long-term clinical aspects, which might need medical management.

Dataset Information

A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney.

Publications

A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney.

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