Prematurity disrupts glomeruli development, whereas prematurity and hyperglycemia lead to altered nephron maturation and increased oxidative stress in newborn baboons

BackgroundPremature birth occurs when nephrogenesis is incomplete and has been linked to increased renal pathologies in the adult. Metabolic factors complicating preterm birth may have additional consequences for kidney development. Here, we evaluated the effects of prematurity and hyperglycemia on nephrogenesis in premature baboons when compared with those in term animals.MethodsBaboons were delivered prematurely (67% gestation; n=9) or at term (n=7) and survived for 2-4 weeks. Preterm animals were classified by glucose control during the first 5 days of life: normoglycemic (PtN; serum glucose 50'100 mg/dl, n=6) and hyperglycemic (PtH; serum glucose 150'250 mg/dl, n=3). Kidneys were assessed histologically for glomeruli relative area, maturity, size, and overall morphology. Kidney lysates were evaluated for oxidative damage with 4-hydroxynonenal (4-HNE) antibody.ResultsHistological examination revealed decreased glomeruli relative area (P<0.05), fewer glomerular generations (P<0.01), and increased renal corpuscle area (P<0.001) in preterm compared with those in term animals. Numbers of apoptotic glomeruli were similar between groups. PtH kidneys exhibited reduced nephrogenic zone width (P<0.0001), increased numbers of mature glomeruli (P<0.05), and increased 4-HNE staining compared with those in PtN kidneys.ConclusionPrematurity interrupts normal kidney development, independent of glomerular cell apoptosis. When prematurity is complicated by hyperglycemia; kidney development shifts toward accelerated maturation and increased oxidative stress.