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Disordered oxygen metabolism in early chronic kidney disease
Author(s) -
Singh Prabhleen,
Pham Hai,
Sharik Meaghen,
Murphy Anne,
Petrosyan Susanna,
Thomson Scott,
Blantz Roland
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.691.8
Subject(s) - nephron , reabsorption , hypoxia (environmental) , medicine , endocrinology , kidney , chemistry , oxygen , mitochondrion , nephrectomy , biology , biochemistry , organic chemistry
Structural changes leading to chronic renal hypoxia, implicated in chronic kidney disease (CKD) progression, occur late and do not explain early intrarenal hypoxia. To examine the early functional adaptations that may increase oxygen demand leading to hypoxia, micropuncture and oxygen consumption (QO2) studies were conducted in rats 1 week after subtotal nephrectomy (STN). Although, oxygen delivery (DO 2 ) was lower in STN, renal oxygen extraction (arterial‐venous O 2 content) doubled in STN vs. control (0.014 vs. 0.007, p<0.05). Both QO 2 and (A‐V)O 2 factored for GFR were significantly higher in STN. Single nephron GFR nearly doubled in STN vs. controls (p<0.05) contributing to transport related QO 2 but could not explain the 3‐fold increase in QO 2 /nephron. Proximal reabsorption was lower in STN shifting salt reabsorption to distal sites associated with increased energetic costs. Expression of NADPH oxidase was also increased in STN. Mitochondrial QO 2 revealed lower state3 respiratory capacity and respiratory control ratio (RCR) in STN, suggestive of mitochondrial complex I dysfunction seen in hypoxia. Treatment with hypoxia inducible factor (HIF) inducer, DMOG, significantly improved several parameters (p<0.05) including DO 2 , (A‐V)O 2 ,(A‐V)O 2 /GFR, and mitochondrial state3respiratory capacity and RCR in STN. Major alterations in both mitochondrial and non‐mitochondrial QO 2 in early STN, most of which were corrected with HIF induction.