Widespread kidney anomalies in children with Down syndrome

Postolache, Lavinia; Parsa, Afshin; Simoni, Paolo; Boitsios, Grammatina; Ismaili, Khalid; Schurmans, Thierry; Monier, Anne; Casimir, Georges; Albert, Adelin; Parsa, Cameron F.

doi:10.1007/s00467-022-05455-y

Cited by 8 publications

(3 citation statements)

References 50 publications

(55 reference statements)

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“…The spectrum of CAKUT prevalent in patients with chromosomal abnormalities is well established, with vesicoureteral reflux and lower urinary tract obstruction being predominant [ 10 ]. In addition to CAKUT, a recent report revealed that children with Down syndrome have smaller kidneys and decreased glomerular filtration rate compared to age-matched controls [ 32 ].…”

Section: Postnatal Management By a Pediatrician Pediatric Nephrologis...mentioning

confidence: 99%

CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood

Chevalier

2023

Pediatric Reports

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The global prevalence of chronic kidney disease (CKD) is increasing rapidly, due to increasing environmental stressors through the life cycle. Congenital anomalies of kidney and urinary tract (CAKUT) account for most CKD in children, with a spectrum that can lead to kidney failure from early postnatal to late adult life. A stressed fetal environment can impair nephrogenesis, now recognized as a significant risk factor for the development of adult CKD. Congenital urinary tract obstruction is the leading cause of CKD due to CAKUT and can itself impair nephrogenesis as well as contribute to progressive nephron injury. Early diagnosis by ultrasonography in fetal life by an obstetrician/perinatologist can provide important information for guiding prognosis and future management. This review focuses on the critical role played by the pediatrician in providing timely evaluation and management of the patient from the moment of birth to the transfer to adult care. In addition to genetic factors, vulnerability of the kidney to CKD is a consequence of evolved modulation of nephron number in response to maternal signaling as well as to susceptibility of the nephron to hypoxic and oxidative injury. Future advances in the management of CAKUT will depend on improved biomarkers and imaging techniques.

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Section: Postnatal Management By a Pediatrician Pediatric Nephrologis...mentioning

confidence: 99%

CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood

Chevalier

2023

Pediatric Reports

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“…DS patients exhibit several congenital renal abnormalities that increase susceptibility to long-term kidney disease [5]. Compared to age-matched controls, children with DS exhibit significantly smaller kidney size as well as evidence of impaired renal function [6].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Non-Congenital Cardiac and Renal Complications in Down Syndrome: A Study of 32,936 Patients

Huang,

Wang

et al. 2023

Children

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Background: Individuals with Down syndrome are at a higher risk of cardiac, renal, and other health issues due to a complex disease physiology. However, few data exist on long-term disease risks to guide prevention and care. We aimed to determine the 10-year incidence of cardiac, renal, and urinary tract complications in Down syndrome versus matched controls. Methods: This retrospective cohort study utilized a large collaborative database. We identified 32,444 patients with Down syndrome and matched controls, excluding those with pre-follow-up target events. Covariates included demographics, lifestyle factors, and comorbidities. Outcomes were ischemic heart disease, hypertension, hypothyroidism, epilepsy, urinary tract infections and chronic kidney disease. We calculated unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression and plotted Kaplan–Meier survival curves. Findings: Over 10 years, Down syndrome patients showed a 3.7-fold higher ischemic heart disease risk (95% CI: 3.0–4.6) and a 1.6-fold higher hypertension risk (95% CI: 1.4–1.8) versus controls. Hypothyroidism (HR = 2.0; 95% CI: 1.7–2.4), epilepsy (HR = 4.5; 95% CI: 3.5–5.8), and urinary tract infection (HR = 3.9; 95% CI: 3.4–4.6) risks were also higher. Chronic kidney disease risk was 2.7-fold greater (95% CI: 2.1–3.5). Survival analysis confirmed a significantly higher incidence of all outcomes in Down syndrome (p < 0.0001). Interpretation: This large study found major health challenges in Down syndrome, with risks 3- to 5-fold higher for chronic conditions versus matched controls over 10 years. Though survival remains high with proper care, focusing resources on the prevention and management of complications in this high-risk group can optimize well-being across the lifespan. Future research accounting for limitations here would provide definitive estimates of disease risk in Down syndrome to guide targeted health strategies.

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“…For example, Down syndrome, one of the most commonly diagnosed fetal conditions, is reported to increase the incidence of renal and urologic anomalies and underdevelopment [ 21 ]. Specifically, a decrease in the total weight of fetal kidneys, immature glomeruli, and low filtration rates have been reported, also suggesting a significant attenuation of renal development [ 22 , 23 ].Moreover, fetal distress is considered a risk factor for AF embolism development, although the exact reason for this is not currently known [ 24 ]. Therefore, we hypothesized that the procoagulant activity that can lead to AF embolism may be associated with the CD24+ and CD24+/TF+ EVs.…”

Section: Introductionmentioning

confidence: 99%

Procoagulant Activity in Amniotic Fluid Is Associated with Fetal-Derived Extracellular Vesicles

Butov

Karetnikova

Pershin

et al. 2022

CIMB

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Procoagulant activity in amniotic fluid (AF) is positively correlated with phosphatidylserine (PS) and tissue factor (TF)-expressing(+) extracellular vesicles (EVs). However, it is unknown if pathological fetal conditions may affect the composition, phenotype, and procoagulant potency of EVs in AF. We sought to evaluate EV-dependent procoagulant activity in AF from pregnant people with fetuses with or without diagnosed chromosomal mutations. AF samples were collected by transabdominal amniocentesis and assessed for common karyotype defects (total n = 11, 7 healthy and 4 abnormal karyotypes). The procoagulant activity of AF was tested using a fibrin generation assay with normal pooled plasma and plasmas deficient in factors XII, XI, IX, X, V, and VII. EV number and phenotype were determined by flow cytometry with anti-CD24 and anti-TF antibodies. We report that factor-VII-, X-, or V-deficient plasmas did not form fibrin clots in the presence of AF. Clotting time was significantly attenuated in AF samples with chromosomal mutations. In addition, CD24+, TF+, and CD24+ TF+ EV counts were significantly lower in this group. Finally, we found a significant correlation between EV counts and the clotting time induced by AF. In conclusion, we show that AF samples with chromosomal mutations had fewer fetal-derived CD24-bearing and TF-bearing EVs, which resulted in diminished procoagulant potency. This suggests that fetal-derived EVs are the predominant source of procoagulant activity in AF.

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Widespread kidney anomalies in children with Down syndrome

Cited by 8 publications

References 50 publications

CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood

CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood

Long-Term Non-Congenital Cardiac and Renal Complications in Down Syndrome: A Study of 32,936 Patients

Procoagulant Activity in Amniotic Fluid Is Associated with Fetal-Derived Extracellular Vesicles

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