Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension

Hansell, Peter; Welch, William J.; Blantz, Roland C.; Palm, Fredrik

doi:10.1111/1440-1681.12034

Cited by 227 publications

(226 citation statements)

References 133 publications

(348 reference statements)

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“…13 Subsequently, it was appreciated that hypertension predisposes to kidney failure by inducing renal hypoxia. 147,148 The detrimental effects of hypoxia are exacerbated by hypertension also inducing kidney tissue to generate elevated levels of reactive oxygen species such as superoxide, hydrogen peroxide, peroxynitrite, and hydroxyl radicals. 149 These species are formed by elevated intrarenal angiotensin II binding type 1 angiotensin II receptors that then transduce signals to activate the pro-oxidant enzyme nicotinamide adenine dinucleotide phosphate-oxidase.…”

Section: Hypertensionmentioning

confidence: 99%

Hypoxia: The Force that Drives Chronic Kidney Disease

Colgan

Shelley

2016

Clinical Medicine & Research

120

105

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In the United States the prevalence of end-stage renal disease (ESRD) reached epidemic proportions in 2012 with over 600,000 patients being treated. The rates of ESRD among the elderly are disproportionally high. Consequently, as life expectancy increases and the baby-boom generation reaches retirement age, the already heavy burden imposed by ESRD on the US health care system is set to increase dramatically. ESRD represents the terminal stage of chronic kidney disease (CKD). A large body of evidence indicating that CKD is driven by renal tissue hypoxia has led to the development of therapeutic strategies that increase kidney oxygenation and the contention that chronic hypoxia is the final common pathway to end-stage renal failure. Numerous studies have demonstrated that one of the most potent means by which hypoxic conditions within the kidney produce CKD is by inducing a sustained inflammatory attack by infiltrating leukocytes. Indispensable to this attack is the acquisition by leukocytes of an adhesive phenotype. It was thought that this process resulted exclusively from leukocytes responding to cytokines released from ischemic renal endothelium. However, recently it has been demonstrated that leukocytes also become activated independent of the hypoxic response of endothelial cells. It was found that this endothelium-independent mechanism involves leukocytes directly sensing hypoxia and responding by transcriptional induction of the genes that encode the β2-integrin family of adhesion molecules. This induction likely maintains the long-term inflammation by which hypoxia drives the pathogenesis of CKD. Consequently, targeting these transcriptional mechanisms would appear to represent a promising new therapeutic strategy.

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Section: Hypertensionmentioning

confidence: 99%

Hypoxia: The Force that Drives Chronic Kidney Disease

Colgan

Shelley

2016

Clinical Medicine & Research

120

105

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“…It is also possible that these variants contribute to altered kidney function in late life. Mitochondria are particularly important in the kidney tubules, where oxygen consumption is utilized primarily for active solute transport 53, 54. Proximal tubule cells, in particular, are densely packed with mitochondria, given their high energy requirements and limited capacity for anaerobic metabolism,55 and inherited mitochondrial disorders are often characterized by severe proximal tubular dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Sequence Variants Associated With Blood Pressure Among 2 Cohorts of Older Adults

Buford

Manini

Kairalla

et al. 2018

JAHA

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BackgroundAge‐related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age‐related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencing the mitochondrial genome.Methods and ResultsMitochondrial DNA (mtDNA) data from 1755 participants from the LIFE (Lifestyle Interventions and Independence for Elders) studies and 788 participants from the Health ABC (Health, Aging, and Body Composition) study were evaluated using replication analysis followed by meta‐analysis. Participants were aged ≥69 years, of diverse racial backgrounds, and assessed for systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure. After meta‐analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and mean arterial pressure (m.15924A>G, t‐RNA‐thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001) and mean arterial pressure (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P's<0.0004) were observed. Significant pooled effects on SBP were observed across all transfer RNA regions (P=0.0056) in white participants. The individual and aggregate variant results are statistically significant after multiple comparisons adjustment for the number of mtDNA variants and mitochondrial regions examined.ConclusionsThese results suggest that mtDNA‐encoded variants are associated with variation in SBP and mean arterial pressure among older adults. These results may help identify mitochondrial activities to explain differences in blood pressure in older adults and generate new hypotheses surrounding mtDNA variation and the regulation of blood pressure.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT01072500 and NCT00116194.

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“…Thus, cells with higher metabolic rate per unit mass (e.g., heart) leads to faster biological aging of organs. Vital organs account for 4-6% body mass but account for metabolic rate 15-40 times that of SM and 5-100 times that of AT [44] indicating that vital organs age much faster compared to other organs. Lifetime specific entropy generation for heart is 135 MJ (K kg heart) for Wang-5 and 110.62 MJ/(K kg heart) for Wang-7 essentially due to similar constant metabolic rate for Elia mode for both Kidney and heart.…”

Section: Effects Of 5 Organ Vs 7 Organ Modelsmentioning

confidence: 99%

Section: Effects Of 5 Organ Vs 7 Organ Modelsmentioning

confidence: 99%

Biological Aging and Life Span Based on Entropy Stress via Organ and Mitochondrial Metabolic Loading

Annamalai

Nanda

2017

Entropy

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Abstract:The energy for sustaining life is released through the oxidation of glucose, fats, and proteins. A part of the energy released within each cell is stored as chemical energy of Adenosine Tri-Phosphate molecules, which is essential for performing life-sustaining functions, while the remainder is released as heat in order to maintain isothermal state of the body. Earlier literature introduced the availability concepts from thermodynamics, related the specific irreversibility and entropy generation rates to metabolic efficiency and energy release rate of organ k, computed whole body specific entropy generation rate of whole body at any given age as a sum of entropy generation within four vital organs Brain, Heart, Kidney, Liver (BHKL) with 5th organ being the rest of organs (R5) and estimated the life span using an upper limit on lifetime entropy generated per unit mass of body, σ M,life . The organ entropy stress expressed in terms of lifetime specific entropy generated per unit mass of body organs (kJ/(K kg of organ k)) was used to rank organs and heart ranked highest while liver ranked lowest. The present work includes the effects of (1) two additional organs: adipose tissue (AT) and skeletal muscles (SM) which are of importance to athletes; (2) proportions of nutrients oxidized which affects blood temperature and metabolic efficiencies; (3) conversion of the entropy stress from organ/cellular level to mitochondrial level; and (4) use these parameters as metabolism-based biomarkers for quantifying the biological aging process in reaching the limit of σ M,life . Based on the 7-organ model and Elia constants for organ metabolic rates for a male of 84 kg steady mass and using basic and derived allometric constants of organs, the lifetime energy expenditure is estimated to be 2725 MJ/kg body mass while lifetime entropy generated is 6050 kJ/(K kg body mass) with contributions of 190; 1835.0; 610; 290; 700; 1470 and 95 kJ/K contributed by AT-BHKL-SM-R7 to 1 kg body mass over life time. The corresponding life time entropy stresses of organs are: 1.2; 60.5; 110.5; 110.5; 50.5; 3.5; 3.0 MJ/K per kg organ mass. Thus, among vital organs highest stress is for heart and kidney and lowest stress is for liver. The 5-organ model (BHKL and R5) also shows similar ranking. Based on mitochondrial volume and 5-organ model, the entropy stresses of organs expressed in kJ/K per cm 3 of Mito volume are: 12,670; 5465; 2855; 4730 kJ/cm 3 of Mito for BHKL indicating brain to be highly stressed and liver to be least stressed. Thus, the organ entropy stress ranking based on unit volume of mitochondria within an organ (kJ/(K cm 3 of Mito of organ k)) differs from entropy stress based on unit mass of organ. Based on metabolic loading, the brains of athletes already under extreme mitochondrial stress and facing reduced metabolic efficiency under concussion are subjected to more increased stress. In the absence of non-intrusive measurements for estimating organ-based metabolic rates which can serve as metabolism-based biomarkers for biol...

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Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension

Cited by 227 publications

References 133 publications

Hypoxia: The Force that Drives Chronic Kidney Disease

Hypoxia: The Force that Drives Chronic Kidney Disease

Mitochondrial DNA Sequence Variants Associated With Blood Pressure Among 2 Cohorts of Older Adults

Biological Aging and Life Span Based on Entropy Stress via Organ and Mitochondrial Metabolic Loading

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