Alterations to peritubular capillary structure in a rat model of kidney interstitial fibrosis: Implications for oxygen diffusion

• Published in: Anatomical record (Hoboken, N.J. : 2007) N.J. : 2007), 2024-09
• Main Authors: Gazzard, Sarah E, Cullen-McEwen, Luise A, Nikulina, Marina, Clever, Arnold B, Gardner, Bruce S, Smith, David W, Lee, Chang-Joon, Nyengaard, Jens R, Evans, Roger G, Bertram, John F
• Format: Article
• Language: English
• ISSN: 1932-8486; 1932-8494; 1932-8494
• DOI: 10.1002/ar.25576

Fibrosis and loss of functional capillary surface area may contribute to renal tissue hypoxia in a range of kidney diseases. However, there is limited quantitative information on the impact of kidney disease on the barriers to oxygen diffusion from cortical peritubular capillaries (PTCs) to kidney epithelial tubules. Here, we used stereological methods to quantify changes in total cortical PTC length and surface area, PTC length and surface densities, and diffusion distances between PTCs and kidney tubules in adenine-induced kidney injury. After 7 days of oral gavage of adenine (100 mg), plasma creatinine was 3.5-fold greater than in vehicle-treated rats, while total kidney weight was 83% greater. The total length of PTCs was similar in adenine-treated (1.47 ± 0.23 km (mean ± standard deviation)) to vehicle-treated (1.24 ± 0.24 km) rats, as was the surface density of PTCs (0.025 ± 0.002 vs. 0.024 ± 0.004 μm /μm ). The total surface area of PTCs was 69% greater in adenine-treated than vehicle-treated rats. However, the length density of PTCs was 28% less in adenine-treated than vehicle-treated rats. Diffusion distances, from PTCs to the basal membrane of the nearest renal tubule (108%), and to the mid-point of the cytoplasmic height of the nearest tubular epithelial cell (57%), were markedly increased. These findings indicate that, in adenine-induced kidney injury, expansion of the renal cortical interstitium increases the distance required for diffusion of oxygen from PTCs to tubules, rendering the kidney cortex susceptible to hypoxia.