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- Friederich-Persson, Malou, et al.
(författare)
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Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage : effects of triiodothyronine and dinitrophenol in normoglycemic rats.
- 2013
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Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Springer-Verlag New York. - 0065-2598 .- 2214-8019. - 9781461474111 - 9781461472568 ; 789, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased oxygen metabolism mediated by mitochondrial uncoupling results in decreased kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen metabolism per se can cause intrarenal tissue hypoxia and kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased kidney metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic kidney disease and progression to end-stage renal disease.
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| 2. |
- Nordquist, Lina, et al.
(författare)
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Hypoxia in the diabetic kidney is independent of advanced glycation end-products.
- 2013
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Ingår i: Advances in Experimental Medicine and Biology. - New York, NY : Kluwer Academic Publishers. - 0065-2598 .- 2214-8019. ; 765, s. 185-193
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Tidskriftsartikel (refereegranskat)abstract
- Sustained hyperglycemia is closely associated with increased risk to develop nephropathy. We have previously reported alterations in the intrarenal oxygen metabolism already after the early onset of diabetes. Furthermore, formation of advanced glycation end-products (AGE) is postulated as a major contributor to diabetic nephropathy. We therefore investigated the possible relationship between altered oxygen metabolism and AGE in diabetic kidneys.Normoglycemic and streptozotocin-diabetic rats with and without chronic treatment with aminoguanidine (AGE inhibitor; 600 mg/kg bw/24 h in drinking water) or L-N(6)-(1-Iminoethyl)lysine (L-NIL, iNOS inhibitor, 1 mg/kg bw/24 h in drinking water) were studied 2 weeks after induction of diabetes. Glomerular filtration rate (GFR) was estimated by inulin clearance, oxygen tension (pO(2)) and interstitial pH by microelectrodes and regional renal blood flow (RBF) by laser-Doppler. Histological changes were evaluated on fixed tissue.Glomerular hyperfiltration was unaffected by aminoguanidine, whereas L-NIL normalized GFR in diabetic rats. pO(2) and interstitial pH, but not RBF, were lower in both kidney cortex and medulla compared to control rats, but was unaffected by both chronic treatments. Urinary protein excretion was higher in diabetic rats and unaffected by L-NIL, whereas aminoguanidine paradoxically increased this parameter. Damage scores were similar in all groups.In conclusion, diabetes-induced alterations in intrarenal oxygen metabolism are independent of the AGE pathway, and precede any morphological changes. These findings highlight the early stage of diabetes as being a metabolic disorder also in the kidney.
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| 3. |
- Singh, P., et al.
(författare)
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Renal oxygenation and haemodynamics in acute kidney injury and chronic kidney disease
- 2013
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Ingår i: Clinical and Experimental Pharmacology and Physiology. - : Wiley. - 0305-1870 .- 1440-1681. ; 40:2, s. 138-147
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Tidskriftsartikel (refereegranskat)abstract
- Acute kidney injury (AKI) is a major burden on health systems and may arise from multiple initiating insults, including ischaemia-reperfusion injury, cardiovascular surgery, radiocontrast administration and sepsis. Similarly, the incidence and prevalence of chronic kidney disease (CKD) continues to increase, with significant morbidity and mortality. Moreover, an increasing number of AKI patients survive to develop CKD and end-stage renal disease. Although the mechanisms for the development of AKI and progression to CKD remain poorly understood, initial impairment of oxygen balance likely constitutes a common pathway, causing renal tissue hypoxia and ATP starvation that, in turn, induce extracellular matrix production, collagen deposition and fibrosis. Thus, possible future strategies for one or both conditions may involve dopamine, loop diuretics, atrial natriuretic peptide and inhibitors of inducible nitric oxide synthase, substances that target kidney oxygen consumption and regulators of renal oxygenation, such as nitric oxide and heme oxygenase-1.
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