Environmental and parental risk factors for congenital solitary functioning kidney - a case-control study

Abstract

Background: The etiology of congenital solitary functioning kidney (CSFK) is largely unknown but likely includes various risk factors. We performed a case-control study to compare exposure to environmental and parental risk factors during embryonic kidney development between children with CSFK and healthy controls.

Methods: We included 434 children with CSFK and 1302 healthy controls from the AGORA data- and biobank matched on year of birth. Exposure to potential risk factors was investigated using parental questionnaire data. Crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated for each potential risk factor. Multiple imputation was used to deal with missing values. Confounders for each potential risk factor were selected using directed acyclic graphs.

Results: Maternal stress was newly identified as a risk factor for CSFK (aOR 2.1, 95% CI 1.2-3.5). Known associations with conception using in vitro fertilization/intracytoplasmic sperm injection (aOR 1.8, 95% CI 1.0-3.2), maternal infections during pregnancy (aOR 2.5, 95% CI 1.4-4.7), smoking during pregnancy (aOR 1.4, 95% CI 1.0-2.0), and parental CAKUT (aOR 6.6, 95% CI 2.9-15.1) were confirmed, but previous associations with diabetes and obesity could not be replicated. Folic acid supplement use and younger maternal age seemed to reduce the risk of CSFK (aORs 0.7, 95% CI 0.5-1.0, and 0.8, 95% CI 0.6-1.0, respectively).

Conclusions: Environmental and parental risk factors are likely to be involved in the development of CSFK and future studies should combine genetic, environmental, and gene-environment interaction analyses. Women wanting to become pregnant should consider optimizing their health and lifestyle. A higher-resolution version of the Graphical abstract is available as Supplementary information.

Keywords: Congenital anomalies of the kidney and urinary tract; Environmental risk factors; Etiology; Kidney development; Solitary functioning kidney.

A higher-resolution version of the Graphical abstract is available as Supplementary information

Fig. 1

Flowchart of recruitment and selection of cases and controls. ^aRecruitment via treating physician was performed in the Radboud university medical center (2004–2021) and University Medical Center Utrecht (2013–2021). ^bRecruitment for the SOFIA study was performed via 36 Dutch hospitals, including the Radboud university medical center and University Medical Center Utrecht. Only patients not yet included in the AGORA data- and biobank were invited to participate. ^cExposures only in full questionnaires were infection, diet, and stress