Chronic intermittent hypoxia promotes glomerular hyperfiltration and potentiates hypoxia-evoked decreases in renal perfusion and PO2

Abstract

Introduction: Sleep apnea (SA) is highly prevalent in patients with chronic kidney disease and may contribute to the development and/or progression of this condition. Previous studies suggest that dysregulation of renal hemodynamics and oxygen flux may play a key role in this process. The present study sought to determine how chronic intermittent hypoxia (CIH) associated with SA affects regulation of renal artery blood flow (RBF), renal microcirculatory perfusion (RP), glomerular filtration rate (GFR), and cortical and medullary tissue PO2 as well as expression of genes that could contribute to renal injury. We hypothesized that normoxic RBF and tissue PO2 would be reduced after CIH, but that GFR would be increased relative to baseline, and that RBF, RP, and tissue PO2 would be decreased to a greater extent in CIH vs. sham during exposure to intermittent asphyxia (IA, FiO2 0.10/FiCO2 0.03). Additionally, we hypothesized that gene programs promoting oxidative stress and fibrosis would be activated by CIH in renal tissue.Methods: All physiological variables were measured at baseline (FiO2 0.21) and during exposure to 10 episodes of IA (excluding GFR).Results: GFR was higher in CIH-conditioned vs. sham (p < 0.05), whereas normoxic RBF and renal tissue PO2 were significantly lower in CIH vs. sham (p < 0.05). Reductions in RBF, RP, and renal tissue PO2 during IA occurred in both groups but to a greater extent in CIH (p < 0.05). Pro-oxidative and pro-fibrotic gene programs were activated in renal tissue from CIH but not sham.Conclusion: CIH adversely affects renal hemodynamic regulation and oxygen flux during both normoxia and IA and results in changes in renal tissue gene expression.

Chronic intermittent hypoxia‐induced cardiovascular and renal dysfunction: from adaptation to maladaptation

“…Local kidney inflammation may be driven by altered haemodynamics and decreased tissue oxygen tension ($${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$$). The effect of CIH on glomerular filtration and perfusion pressure is variable with no changes reported in one study (O'Neill et al., 2019), whereas hyperfiltration and reduced renal blood flow (RBF) is reported in a more recent study (Kious et al., 2023), perhaps related to differences in the pattern of CIH, state (anaesthetized vs . conscious) and/or the use of different anaesthetic agents in the two studies.…”

“…conscious) and/or the use of different anaesthetic agents in the two studies. However, in both studies, there is consensus that exposure to a moderate paradigm of CIH (6.5–10.0% O 2 , 10–20 cycles/h, 8 h/day for 2 weeks) causes a reduction in renal cortical and medullary $${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$$ (Kious et al., 2023; O'Neill et al., 2019)…”

“…In contrast, long‐term CIH (8% O 2 , 30 cycles/h, 12 h/day, for 8 weeks) induced significant renal inflammation and downregulation of antioxidants along with significant renal oxidative damage, cell death and fibrosis (Sun et al., 2012). Intermediate exposure (10% O 2 , 20 cycles/h, 8 h/day, for 2 weeks) is associated with activation of pro‐oxidative and pro‐fibrotic gene programs (Kious et al., 2023). Consistent with the notion of a temporal response to CIH, an increase in antioxidant defence was shown using a mild short‐term CIH paradigm (5% O 2 , 5.6 cycles/h, 10.5 h/day) by Correia et al.…”