Pathophysiology of congenital diaphragmatic hernia. IV: Renal hyperplasia is associated with pulmonary hypoplasia.
The hypothesis of this article is that growth of the fetal lung is stimulated by a pulmonary growth factor (PGF) produced by the kidneys, which is modulated by a feedback signal from the lungs, a pulmonary-derived renotropin (PDR). In the fetus with pulmonary hypoplasia (PH), the lungs may maximally stimulate this feedback loop to release more PDR, resulting in continual stimulation of the kidneys and renal enlargement. If such a schema plays a role in the pathophysiology of PH, newborn infants with congenital diaphragmatic hernia (CDH) or chronic amniotic fluid leak (CAFL) should have enlarged kidneys. To investigate this hypothesis, we created models of CDH in fetal lambs and CAFL in fetal rabbits, and then analyzed lung (Lu) and kidney (K) growth. When compared to controls, newborn CDH lambs had significantly smaller lungs and larger kidneys. The lungs were hypoplastic as defined by either decreased lung weight/body weight (LuW/BW), lung DNA/body weight (Lu DNA/BW), or lung total protein/body weight (LuTP/BW) (P < .01). Renal hyperplasia was confirmed by KW/BW, K DNA/BW (P < .01), and KTP/BW (P < .05). An inverse relationship between lung size and kidney size could be described by the equation KW/BW = 1.04 - 0.12 LuW/BW (r = -.75). The CAFL model in newborn rabbits produced severe oligohydramnios when compared with controls (P < .01). This resulted in fetuses with smaller lungs and larger kidneys as compared with those of controls. The lungs were significantly smaller and more hypoplastic than controls when compared by LuW (P < .01), LuW/BW (P < .01), Lu DNA/BW (P < .05), and Lu TP/BW (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Hosoda
Y
Y
Buffalo Institute of Fetal Therapy, Division of Pediatric Surgery, Children's Hospital of Buffalo, NY 14222.
Rossman
J E
JE
Glick
P L
PL
D000653:Amniotic Fluid / Q000502:physiology; D000818:Animals; D001835:Body Weight; D004247:DNA / Q000032:analysis; D005260:Female; D005315:Fetal Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006548:Hernia, Diaphragmatic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D006965:Hyperplasia; D007668:Kidney / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000002:abnormalities* / Q000254:growth & development / Q000503:physiopathology*; D008954:Models, Biological; D009929:Organ Size; D011247:Pregnancy; D011817:Rabbits
D004247:DNA