Preterm birth and ventilation decrease surface density of glomerular capillaries in lambs, regardless of postnatal respiratory support mode

Abstract

Background Prematurity is often complicated by respiratory support, including invasive mechanical ventilation (IMV) and non-invasive support (NIS). Compared to IMV, NIS reduces injury to the lung and brain. Prematurity may also disrupt glomerular architecture. Whether NIS differentially affects glomerular architecture is incompletely understood. We hypothesized that IMV would lead to greater disruption of glomerular architecture than NIS. Methods This is a secondary analysis of kidneys from moderately preterm lambs delivered at ∼131d gestation (term ∼150d) that had antenatal steroid exposure and surfactant treatment before resuscitation by IMV. At ∼3h of age, half of the lambs were switched to NIS. Support was for 3d or 21d. Structural indices of glomerular architecture were quantified. Results The number of glomerular generations was unaffected by moderate preterm birth and respiratory support, either IMV or NIS. At 3d and 21d of IMV or NIS, glomerular capillary surface density was not different. Glomerular capillary surface density was significantly lower in the inner and outer cortex compared to unventilated gestation age-matched or postnatal age-matched reference lambs. Conclusion Moderate preterm birth and invasive or non-invasive respiratory support decreases glomerular capillarisation in the lamb kidney. This adverse effect on glomerular development may contribute to increased risk for adult-onset hypertension and renal dysfunction.

Prematurity, perinatal inflammatory stress, and the predisposition to develop chronic kidney disease beyond oligonephropathy

“…Sutherland and Staub both used preterm sheep models with sheep born at 130 days of gestation (comparable to 35 weeks gestation in humans) [ 63 , 64 ]. Both studies found normal glomerular numbers, which can be explained by the gestational age by which nephrogenesis is complete.…”

“…Sutherland described preterm animals to have a reduced glomerular capillary length, surface area, and total kidney filtration surface area [ 63 ]. Staub compared the effect of 3 and 21 days of mechanical ventilation [ 64 ]. After preterm birth, glomerular capillarization increased.…”

“…After preterm birth, glomerular capillarization increased. However, mechanical ventilation inhibits this expected growth and therefore decreases the glomerular capillary development even further [ 64 ]. In a baboon model of prematurity, Guhbaju found an increase in abnormal glomeruli, defined by a cystic Bowman’s space and shrunken glomerular tuft [ 29 ].…”

Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age

“…1). Details of the perinatal steps were reported by our group previously (5,44,61,66,71). Briefly, the fetuses were exposed to antenatal steroids for 48 h before Cesarean section (exit procedure) delivery.…”

“…The lambs were given Beuthanasia solution (0.25 ml/kg; Intervet, Madison, NJ) followed by potassium chloride (10 mEq; Hospira, Lake Forest, IL) intravenously. Terminal tissue collection has been reported by our group (5,44,61,66,71). Briefly, the entire left lung was insufflated with fixative and processed by systematic, uniform, random methods for quantitative histology (39).…”