A Common Variant of the PAX2 Gene Is Associated with Reduced Newborn Kidney Size

Quinlan, Jacklyn; Lemire, Mathieu; Hudson, Thomas J.; Qu, Hui‐Qi; Benjamin, Alice; Roy, A. K.; Pascuet, Elena; Goodyer, Meigan; Raju, Chandhana; Zhang, Zhao; Houghton, Fiona; Goodyer, Paul

doi:10.1681/asn.2006101107

Cited by 93 publications

(84 citation statements)

References 32 publications

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“…It is indeed conceivable that milder variants of these syndromes would not produce the complete phenotype such that parents and siblings may be relatively asymptomatic. In support of this, a common haplotype affecting PAX2 expression levels has been identified in patients with hypoplastic kidneys without renal coloboma syndrome (43). The fact that the genital tracts are derived from the Wolffian and Mu¨llerian ducts provides an initial indication as to which genes may be affected (as heterozygous) in the parents of BRA fetuses.…”

Section: Clinical Considerationsmentioning

confidence: 88%

Plumbing in the embryo: developmental defects of the urinary tracts

Uetani

Bouchard

2009

Clinical Genetics

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Kidney and urinary tract malformations are among the most frequent developmental defects identified in newborns. Ranging from asymptomatic to neonatal lethal, these malformations represent an important clinical challenge. Recent progress in understanding the developmental origin of urinary tract defects in the mouse and other animal models suggests a new framework for the interpretation of these defects in humans. Gene inactivation studies in mice provided invaluable information on the formation of the Wolffian duct, a central component of embryonic renal development, on ureter and kidney induction as well as on distal ureter maturation. All three developmental processes are crucial for normal urinary tract morphogenesis. A failure to complete these developmental steps is responsible for a spectrum of kidney and urinary tract malformations including renal agenesis, renal dysplasia, vesicoureteral reflux, hydroureter, hydronephrosis and ureterocele. Surprisingly, distal ureter maturation, the process by which the ureter is displaced from the Wolffian duct to its final position within the bladder wall, has only recently been characterized at the morphological level. Anomalies in this process are emerging as a major source of urinary tract developmental defects. This review is aimed at bridging the current knowledge on the morphological and molecular events identified in the mouse, together with clinical observations of urinary tract malformation in humans.

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Section: Clinical Considerationsmentioning

confidence: 88%

Plumbing in the embryo: developmental defects of the urinary tracts

Uetani

Bouchard

2009

Clinical Genetics

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“…Search for common polymorphisms in several genes known to participate in kidney development have shown correlations between altered gene transcription and newborn kidney size, which is proportional to nephron number (Table 1) 18 . These studies have been conducted in primarily Caucasian populations, therefore implications in other populations need to be investigated 18,46,47 . The molecular mechanisms regulating nephrogenesis are expertly reviewed elsewhere 48 .…”

Section: Developmental Determinants Of Low Nephron Numbermentioning

confidence: 99%

Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease

et al. 2013

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Developmental programming of non-communicable diseases is now an established paradigm. With respect to hypertension and chronic kidney disease, adverse events experienced in utero can affect development of the fetal kidney and reduce final nephron number. Low birth weight and prematurity are the most consistent clinical surrogates for a low nephron number, and are associated with increased risk of hypertension, proteinuria and kidney disease in later life. Rapid weight gain in childhood or adolescence further compounds these risks. Low birth weight, prematurity and rapid childhood weight gain should alert clinicians to an individual's life-long risk of hypertension and kidney disease, prompting education to minimize additional risk factors and ensuring follow-up. Birth weight and prematurity are significantly impacted by maternal nutrition and health during pregnancy. Optimization of maternal health and early childhood nutrition could therefore attenuate this programming cycle and reduce the global burden of hypertension and kidney disease in the future.

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“…16,17 Left and right kidney volumes (LKVs and RKVs, respectively) were calculated using the following formula for volume of an ellipsoid: [kidney volume = 4/3Π (length/2)(height/2) (width/2)]. 3 Total kidney volume (TKV) was calculated as the sum of LKV and RKV. Subsequently, TKV was normalized for body surface area (TKV/BSA).…”

Section: Kidney Volume Measurementmentioning

confidence: 99%

“…2 Despite extensive research, still little is known about how final nephron number is set. 3 However, genetic studies in humans and mice have provided valuable insights into genetic contribution and molecular mechanisms leading to normal nephron endowment and renal hypoplasia. 4 In addition, El Kares et al recently hypothesized that congenital nephron number is a multifactorial trait controlled by the interaction of environmental factors and genetic variants that influence the extent of branching nephrogenesis during foetal life.…”

Section: Introductionmentioning

confidence: 99%

An insertion/deletion ACE polymorphism and kidney size in Polish full-term newborns

Kaczmarczyk

Łoniewska

Kuprjanowicz

et al. 2012

J Renin Angiotensin Aldosterone Syst

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The number of nephrons is a multifactorial trait controlled by the interaction of environmental factors and genetic variants that influence the extent of branching nephrogenesis during foetal life. A correlation between renal mass and nephron number in newborns allows the use of the total kidney volume at birth as a surrogate for congenital nephron number. Since the renin-angiotensin system plays an important role in renal development we hypothesized that the common, functional insertion/deletion (I/D) polymorphism in the ACE gene might be responsible for the variation in kidney size amongst healthy individuals. We recruited 210 healthy Polish full-term newborns born to healthy women with uncomplicated pregnancies. The kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left kidney volume and right kidney volume. TKV was normalized to body surface area (TKV/BSA). The I and D alleles were identified using polymerase chain reaction. TKV/BSA in newborns carrying at least one insertion ACE allele was significantly reduced by approximately 8% as compared with homozygous newborns for the D allele (DD genotype) (105.1±23.6 vs. 114.2±28.2 cm 3 /m 2 , p<0.05). The results of this study suggest that I/D ACE polymorphism may account for subtle variation in kidney size at birth, which reflects congenital nephron endowment.

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A Common Variant of the PAX2 Gene Is Associated with Reduced Newborn Kidney Size

Cited by 93 publications

References 32 publications

Plumbing in the embryo: developmental defects of the urinary tracts

Plumbing in the embryo: developmental defects of the urinary tracts

Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease

An insertion/deletion ACE polymorphism and kidney size in Polish full-term newborns

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