Effects of sex and uninephrectomy on glomerular capillary morphology in rats
Authors: Coker Zackarias , Chivers Jacqueline , Fritz Rolf , Polichnowski Aaron 
Published: May 2023

The progression of chronic kidney disease (CKD) occurs faster in males (M); however, the underlying mechanisms remain poorly understood. A potential contributing factor to sex differences in CKD progression is differences in glomerular capillary morphology. Glomerular capillaries with larger radii or longer lengths may predispose capillaries to barotrauma-induced injury. The goal of the present study was to assess glomerular capillary morphology in M vs. female (F) rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (RCAP) and length (LCAP) would be greater in M rats.This study utilized rats (8-11-week old, Charles River) with intact kidneys (n=4 M, n=4 F) and UNX (n=4 M, n=4 F) provided a 0.4% NaCl diet and water ad libitum. Kidneys were perfusion-fixed with 2% paraformaldehyde and 2.5% glutaraldehyde in phosphate buffered saline (pH=7.4). The left kidney was excised and a 3 mm transverse section through the midline of the kidney was selected for further processing. Multiple 1 mm3 cubes were randomly excised from the left, middle, and right regions of the outer cortex and embedded in EPONTM. The 1 mm3 cubes were sectioned (1 μm), placed on slides, and stained with toluidine blue. Four glomeruli from each region were randomly selected for stereological analysis using STEPanizer (Tschanz SA et al. J. Microsc. 243(1):47-59, 2011). Values of RCAP and LCAP were derived using standard stereological formulas (Nyengaard JR J. Am. Soc. Nephrol. 10(5):1100-1123, 1999). Effects of sex and UNX on body weight (BW), kidney weight (KW), glomerular volume (VG), RCAP, and LCAP were assessed with a 2-way ANOVA with Sidak post hoc analysis. All data are mean±SE and P<0.05 was considered statistically significant.In M vs. F rats with intact kidneys, BW (289±7 vs. 230±6 g) was greater (P<0.05) in M, but no significant differences were observed in KW (1.4±0.1 vs. 1.2±0.1 g), VG (0.65± 0.02 vs. 0.62±0.04 x 106 μm3), RCAP (2.8±0.1 vs. 2.8±0.1 μm), or LCAP (7.3±0.3 vs. 7.1±0.1 mm). In F rats with UNX vs. intact kidneys, BW was not significantly different; however, KW, VG, RCAP, and LCAP were 1.1-1.6-fold greater (P<0.05) in rats with UNX. In M rats with UNX vs. intact kidneys, BW, KW, and VG were 2-3.5-fold greater (P<0.0001), and RCAP and LCAP were 1.1-1.5-fold greater (P<0.05) in rats with UNX. M rats with UNX exhibited a greater (P<0.0005) BW (560±21 vs. 270±11 g), KW (4.2±0.2 vs. 1.8±0.1 g), VG (1.3±0.1 vs. 1.0±0.01 x 106 μm3), and LCAP (11.0±0.3 vs. 9.7±0.3 mm) as compared to F rats with UNX. RCAP was similar in M and F rats with UNX (3.3±0.1 vs. 3.1±0.1 μm). These data indicate that M rats exhibit greater compensatory increases in LCAP following UNX as compared to F rats. The greater LCAP in M may result in reduced podocyte density and contribute, in part, to their greater susceptibility to hypertensive injury and CKD progression as compared to F rats. NIH (HL150467) and East Tennessee State University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.