The Role of the Kidney in Lung Growth and Maturation in the Setting of Obstructive Uropathy and Oligohydramnios

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Abstract
The contribution of the kidneys to lung development, which includes growth and maturation, is uncertain but it appears to be complex. Obstructive uropathy with oligohydramnios produces pulmonary hypoplasia characterized by small lungs (decreased lung volume/body weight) and retarded maturation (reduced total airspace). Lung growth and maturation were studied in a model of early gestation obstructive uropathy to understand better their relationship and their prenatal regulation. Of 26 fetal sheep studied at near term (135 days of gestation) 9 had bladder obstruction created at 60 days of gestation, 11 had bladder obstruction at 60 days with in utero decompression at 95 days, and 6 served as controls and shams. Amniotic fluid volume was measured, kidneys were prepared and evaluated histologically, lungs were inflation-fixed and volumes were measured, and airspace volume percentage was measured morphometrically. Experimental and serendipitous variations in the condition of the kidneys and amniotic fluid at delivery permitted an analysis of the contribution of the kidneys and the amniotic fluid to lung growth and maturation. Impairment of growth and maturation was dissociated in certain animals, and this dissociation was referable to the histological status of the kidneys and the presence or absence of amniotic fluid at delivery. Growth was normal when amniotic fluid was present or likely to have been present in late gestation, even with structurally damaged kidneys. With severe renal damage amniotic fluid was not restored even with in utero decompression and it resulted in severely impaired lung growth. Maturation was normal only in the presence of amniotic fluid and intact kidneys. The dissociation of lung growth and structural maturity suggests their independent regulation. The data suggest that the kidneys are important in early lung growth, while the presence of amniotic fluid contributes to growth later in gestation. Lung maturity requires both factors, suggesting a primary kidney contribution with the amniotic fluid acting in a permissive or supportive role.