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Pathophysiology of congenital diaphragmatic hernia. IV: Renal hyperplasia is associated with pulmonary hypoplasia
Y Hosoda1, J E Rossman, P L Glick
1Buffalo Institute of Fetal Therapy, Division of Pediatric Surgery, Children's Hospital of Buffalo, NY 14222.
Insights
Fetal lung hypoplasia is linked to enlarged kidneys in animal models. This suggests a potential feedback loop between lung development and kidney growth in conditions like congenital diaphragmatic hernia.
Area of Science:
- Developmental Biology
- Renal Physiology
- Fetal Medicine
Background:
- Fetal lung growth is regulated by complex signaling pathways.
- Pulmonary hypoplasia (PH) is a critical condition in newborns.
- The interplay between fetal lung and kidney development is not fully understood.
Purpose of the Study:
- To test the hypothesis that fetal kidney-produced pulmonary growth factor (PGF) and lung-derived renotropin (PDR) influence fetal lung and kidney growth.
- To investigate the role of this feedback loop in the pathophysiology of pulmonary hypoplasia.
Main Methods:
- Created models of congenital diaphragmatic hernia (CDH) in fetal lambs and chronic amniotic fluid leak (CAFL) in fetal rabbits.
- Analyzed fetal lung and kidney growth parameters, including weight, DNA, and protein content relative to body weight.
Main Results:
- Newborn lambs with CDH exhibited significantly smaller lungs and larger kidneys compared to controls.
- Fetal rabbits with CAFL showed smaller, hypoplastic lungs and enlarged kidneys.
- An inverse relationship was observed between lung and kidney size in CDH models.
Conclusions:
- The study supports a model where pulmonary hypoplasia may lead to renal enlargement through a feedback mechanism.
- These findings suggest a potential link between lung development and kidney growth regulation in fetal conditions.
- The results highlight the importance of understanding fetal organ development and interdependencies.
Abstract:
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)