Table 1.

Experimental models and mechanisms of reduced nephron number

Experimental ModelProposed Mechanism of Nephron Number ReductionReference
Maternal low-protein diet↑apoptosis in metanephros and postnatal kidney169–171
Altered gene expression in developing kidney
Altered gene methylation
↓placental 11-βHSD2 expression
Maternal vitamin A restriction↓branching of ureteric bud172
? maintenance of spatial orientation of vascular development
↓c-ret expression
Maternal iron restriction? reduced oxygen delivery173
? altered glucocorticoid responsiveness
? altered micronutrient availability
Gestational glucocorticoid exposure↑fetal glucocorticoid exposure108,174–176
? enhanced tissue maturation
↑glucocorticoid receptor expression
↑1α- and β-ATPase expression
↓renal and adrenal 11-βHSD2 expression
Uterine artery ligation/embolization↑proapoptotic gene expression177,178
↓antiapoptotic gene expression
Altered gene methylation
Altered renin-angiotensin gene expression
Maternal diabetes/hyperglycemia↓IGF-11/mannose-6-phosphate receptor expression64,179,180
Altered IGF-11 activity/bioavailability
Activation of NF-κB
Gestational drug exposure181–184
    gentamicin↓branching morphogenesis
    β lactams↑mesenchymal apoptosis
    cyclosporineArrest of nephron formation
    ethanol? via reduced vitamin A levels
    COX2 inhibitorsAffects prostaglandins
  • 11-βHSD2, 11β-hydroxysteroid dehydrogenase 2; COX, cyclooxygenase. Adapted from: Luyckx VA, Brenner BM: Nephron endowment. In: The Kidney, 8th Ed., edited by Brenner BM, Philadelphia, W.B. Saunders, 2008, pp 654–673.