Effects of preterm birth and ventilation on glomerular capillary growth in the neonatal lamb kidney

Abstract

Objectives Preterm birth is linked to the development of hypertension later in life. This may relate to impaired glomerular capillary growth following preterm birth. The aim of this study was to determine the effects of preterm birth, and/or ventilation, on glomerular capillary growth in the neonatal lamb kidney. Methods Four experimental groups were analysed: 1) Preterm lambs delivered at 130d gestation (term=147d) and mechanically ventilated for 3 days (Preterm ventilated: n=9); 2) 133d gestational controls (Gestational control: n=5); 3) Term controls, unassisted breathing for 3 days (Term control: n=8); and 4) Term lambs ventilated for 3 days (Term ventilated: n=5). In perfusion-fixed kidneys, total nephron number and average total capillary length and surface area per renal corpuscle were stereologically assessed and total renal filtration surface area (TRFSA) calculated. Results In comparison to term controls, preterm lambs had significantly reduced glomerular capillary length, surface area and TRFSA, indicative of a low renal functional capacity. Term ventilated lambs exhibited significantly reduced glomerular capillary length and surface area compared to term controls, indicating that ventilation impairs glomerular capillary growth independently of preterm birth. Conclusion Impaired glomerular capillary growth and subsequent reduced TRFSA following preterm birth may mediate the increased predisposition to hypertension later in life.

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

“…Those findings led to this secondary analysis of the kidneys. The detrimental effect of prematurity accompanied by IMV specifically on glomerular architecture development after completion of glomerulogenesis in this study is consistent with reduced total renal filtration surface and reduced glomerular capillary length during IMV in moderately preterm lambs 20 . Our study adds the insight that NIS also decreases glomerular architectural development equally in the kidney of moderately premature lambs.…”

“…A new report by our group focused on prematurity as an influential factor by comparing glomerular stereological parameters between preterm and term lambs 20 . That study provides the insight that regardless of being preterm or term, lambs supported by IMV for 3d have significantly decreased glomerular capillary length and surface area, and reduced total renal filtration surface area.…”

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).…”

A practical guide to the stereological assessment of glomerular number, size, and cellular composition

“…Although these techniques are relatively labor-intensive and time-consuming, they are considered the gold-standard techniques for these measurements at the present time. Many of these techniques have been developed or refined in John Bertram's laboratory (Bertram, 2001;Cullen-McEwen, Armitage, Nyengaard, & Bertram, 2012;Cullen-McEwen, Douglas-Denton, & Bertram, 2012;Puelles et al, 2014;Puelles et al, 2016) and are routinely used in our laboratory (often in collaboration with researchers from the Bertram lab) (Gubhaju et al, 2009;Maka et al, 2008;Mitchell, Louey, Cock, Harding, & Black, 2004;Ryan et al, 2018;Ryan, Atik, De Matteo, Harding, & Black, 2013;Sutherland et al, 2013;Sutherland, Ryan, Dahl, Albertine, & Black, 2016). In this article, we describe in "step-by-step" detail a number of these stereological techniques (including details on how to apply these techniques in the assessment of kidneys of differing sizes and levels of maturity), with the aim that these methodologies will be a valuable resource to other researchers in the field.…”