scholarly journals Temporal Alterations in Mitochondrial β-Oxidation and Oxidative Stress Aggravate Chronic Kidney Disease Development in 5/6 Nephrectomy Induced Renal Damage

2020 ◽  
Vol 21 (18) ◽  
pp. 6512
Author(s):  
Omar Emiliano Aparicio-Trejo ◽  
Pedro Rojas-Morales ◽  
Sabino Hazael Avila-Rojas ◽  
Juan Carlos León-Contreras ◽  
Rogelio Hernández-Pando ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Time Course ◽  
Renal Damage ◽  
Complex Iii ◽  
Early Event ◽  
Mitochondrial Bioenergetics ◽  
Ckd Progression ◽  
Atp Production ◽  
Time Course Study

Five-sixths nephrectomy (5/6Nx) model is widely used for studying the mechanisms involved in chronic kidney disease (CKD) progression, a kidney pathology that has increased dramatically in recent years. Mitochondrial impairment is a key mechanism that aggravates CKD progression; however, the information on mitochondrial bioenergetics and redox alterations along a time course in a 5/6Nx model is still limited and in some cases contradictory. Therefore, we performed for the first time a time-course study of mitochondrial alterations by high-resolution respirometry in the 5/6Nx model. Our results show a decrease in mitochondrial β-oxidation at early times, as well as a permanent impairment in adenosine triphosphate (ATP) production in CI-linked respiration, a permanent oxidative state in mitochondria and decoupling of these organelles. These pathological alterations are linked to the early decrease in complex I and ATP synthase activities and to the further decrease in complex III activity. Therefore, our results may suggest that mitochondrial bioenergetics impairment is an early event in renal damage, whose persistence in time aggravates CKD development in the 5/6Nx model.

Hypoxia in chronic kidney disease: towards a paradigm shift?

2020 ◽  
Author(s):  
Anna Faivre ◽  
Carsten C Scholz ◽  
Sophie de Seigneux
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Time Course ◽  
Inflammatory Responses ◽  
Adult Population ◽  
Causative Role ◽  
Ckd Progression ◽  
Classical View ◽  
Hif Pathway

Abstract Chronic kidney disease (CKD) is defined as an alteration of kidney structure and/or function lasting for >3 months [1]. CKD affects 10% of the general adult population and is responsible for large healthcare costs [2]. Since the end of the last century, the role of hypoxia in CKD progression has controversially been discussed. To date, there is evidence of the presence of hypoxia in late-stage renal disease, but we lack time-course evidence, stage correlation and also spatial co-localization with fibrotic lesions to ensure its causative role. The classical view of hypoxia in CKD progression is that it is caused by peritubular capillary alterations, renal anaemia and increased oxygen consumption regardless of the primary injury. In this classical view, hypoxia is assumed to further induce pro-fibrotic and pro-inflammatory responses, as well as oxidative stress, leading to CKD worsening as part of a vicious circle. However, recent investigations tend to question this paradigm, and both the presence of hypoxia and its role in CKD progression are still not clearly demonstrated. Hypoxia-inducible factor (HIF) is the main transcriptional regulator of the hypoxia response. Genetic HIF modulation leads to variable effects on CKD progression in different murine models. In contrast, pharmacological modulation of the HIF pathway [i.e. by HIF hydroxylase inhibitors (HIs)] appears to be generally protective against fibrosis progression experimentally. We here review the existing literature on the role of hypoxia, the HIF pathway and HIF HIs in CKD progression and summarize the evidence that supports or rejects the hypoxia hypothesis, respectively.

scholarly journals New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the Literature

2020 ◽  
Vol 22 (1) ◽  
pp. 43
Author(s):  
Irina Lousa ◽  
Flávio Reis ◽  
Idalina Beirão ◽  
Rui Alves ◽  
Luís Belo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Renal Damage ◽  
Recent Literature ◽  
Therapeutic Interventions ◽  
Review Of The Literature ◽  
Medical Need ◽  
Early Use ◽  
Reasonable Approach

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients’ prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process.

scholarly journals Gut Microbiome Composition Remains Stable in Individuals with Diabetes-Related Early to Late Stage Chronic Kidney Disease

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 19
Author(s):  
Ashani Lecamwasam ◽  
Tiffanie M. Nelson ◽  
Leni Rivera ◽  
Elif I. Ekinci ◽  
Richard Saffery ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Relative Abundance ◽  
Cross Sectional Study ◽  
Early Event ◽  
Sectional Study ◽  
Cross Sectional ◽  
Microbiome Composition ◽  
Stool Samples ◽  
Late Stages

(1) Background: Individuals with diabetes and chronic kidney disease display gut dysbiosis when compared to healthy controls. However, it is unknown whether there is a change in dysbiosis across the stages of diabetic chronic kidney disease. We investigated a cross-sectional study of patients with early and late diabetes associated chronic kidney disease to identify possible microbial differences between these two groups and across each of the stages of diabetic chronic kidney disease. (2) Methods: This cross-sectional study recruited 95 adults. DNA extracted from collected stool samples were used for 16S rRNA sequencing to identify the bacterial community in the gut. (3) Results: The phylum Firmicutes was the most abundant and its mean relative abundance was similar in the early and late chronic kidney disease group, 45.99 ± 0.58% and 49.39 ± 0.55%, respectively. The mean relative abundance for family Bacteroidaceae, was also similar in the early and late group, 29.15 ± 2.02% and 29.16 ± 1.70%, respectively. The lower abundance of Prevotellaceae remained similar across both the early 3.87 ± 1.66% and late 3.36 ± 0.98% diabetic chronic kidney disease groups. (4) Conclusions: The data arising from our cohort of individuals with diabetes associated chronic kidney disease show a predominance of phyla Firmicutes and Bacteroidetes. The families Ruminococcaceae and Bacteroidaceae represent the highest abundance, while the beneficial Prevotellaceae family were reduced in abundance. The most interesting observation is that the relative abundance of these gut microbes does not change across the early and late stages of diabetic chronic kidney disease, suggesting that this is an early event in the development of diabetes associated chronic kidney disease. We hypothesise that the dysbiotic microbiome acquired during the early stages of diabetic chronic kidney disease remains relatively stable and is only one of many risk factors that influence progressive kidney dysfunction.

scholarly journals A phosphate and calcium-enriched diet promotes progression of 5/6-nephrectomy-induced chronic kidney disease in C57BL/6 mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Radloff ◽  
N. Latic ◽  
U. Pfeiffenberger ◽  
C. Schüler ◽  
S. Tangermann ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Calcium Phosphate ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Time Course ◽  
Bone Mineralization ◽  
Fibroblast Growth Factor 23 ◽  
Functional Decline ◽  
Left Ventricular ◽  
Normal Diet

AbstractC57BL/6 mice are known to be rather resistant to the induction of experimental chronic kidney disease (CKD) by 5/6-nephrectomy (5/6-Nx). Here, we sought to characterize the development of CKD and its cardiac and skeletal sequelae during the first three months after 5/6-Nx in C57BL/6 mice fed a calcium- and phosphate enriched diet (CPD) with a balanced calcium/phosphate ratio. 5/6-NX mice on CPD showed increased renal fibrosis and a more pronounced decrease in glomerular filtration rate when compared to 5/6-Nx mice on normal diet (ND). Interestingly, despite comparable levels of serum calcium, phosphate, and parathyroid hormone (PTH), circulating intact fibroblast growth factor-23 (FGF23) was 5 times higher in 5/6-Nx mice on CPD, relative to 5/6-Nx mice on ND. A time course experiment revealed that 5/6-Nx mice on CPD developed progressive renal functional decline, renal fibrosis, cortical bone loss, impaired bone mineralization as well as hypertension, but not left ventricular hypertrophy. Collectively, our data show that the resistance of C57BL/6 mice to 5/6-Nx can be partially overcome by feeding the CPD, and that the CPD induces a profound, PTH-independent increase in FGF23 in 5/6-Nx mice, making it an interesting tool to assess the pathophysiological significance of FGF23 in CKD.

scholarly journals Progressive Reduction in Mitochondrial Mass Is Triggered by Alterations in Mitochondrial Biogenesis and Dynamics in Chronic Kidney Disease Induced by 5/6 Nephrectomy

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 349
Author(s):  
Rodrigo Prieto-Carrasco ◽  
Fernando E. García-Arroyo ◽  
Omar Emiliano Aparicio-Trejo ◽  
Pedro Rojas-Morales ◽  
Juan Carlos León-Contreras ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Mitochondrial Biogenesis ◽  
Renal Mass ◽  
Renal Damage ◽  
Peroxisome Proliferator ◽  
Progressive Reduction ◽  
Ckd Progression ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Mass ◽  
Mitochondrial Impairment

The five-sixth nephrectomy (5/6Nx) model is widely used to study the mechanisms involved in chronic kidney disease (CKD) progression. Mitochondrial impairment is a critical mechanism that favors CKD progression. However, until now, there are no temporal studies of the change in mitochondrial biogenesis and dynamics that allow determining the role of these processes in mitochondrial impairment and renal damage progression in the 5/6Nx model. In this work, we determined the changes in mitochondrial biogenesis and dynamics markers in remnant renal mass from days 2 to 28 after 5/6Nx. Our results show a progressive reduction in mitochondrial biogenesis triggered by reducing two principal regulators of mitochondrial protein expression, the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and the peroxisome proliferator-activated receptor alpha. Furthermore, the reduction in mitochondrial biogenesis proteins strongly correlates with the increase in renal damage markers. Additionally, we found a slow and gradual change in mitochondrial dynamics from fusion to fission, favoring mitochondrial fragmentation at later stages after 5/6Nx. Together, our results suggest that 5/6Nx induces the progressive reduction in mitochondrial mass over time via the decrease in mitochondrial biogenesis factors and a slow shift from mitochondrial fission to fusion; both mechanisms favor CKD progression in the remnant renal mass.

scholarly journals Analysis of blood gas beyond bicarbonate in outpatients with stage 3–5 chronic kidney disease

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Ilter Bozaci ◽  
Ali Nazmi Can Doğan ◽  
Merve Aktar ◽  
Alev Mahşer ◽  
Gizem Yıldırım ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Odds Ratio ◽  
Mixed Type ◽  
Base Excess ◽  
Blood Gas ◽  
Ckd Progression ◽  
Group 1

AbstractObjectivesMetabolic acidosis is a common disorder seen in course of chronic kidney disease (CKD). In this study, we aimed to investigate the association of Base excess (BE), Anion gap (AG) and Delta Ratio with progression of CKD, renal replacement therapy (RRT) requirement and mortality in patients with stage 3–5 CKD.MethodsA total of 212 patients with stage 3–5 CKD were included in this study. Patients were divided into two groups according to the baseline BE level. Patients were also grouped according to the delta ratio such as non- AG, High AG and mixed type.ResultsMean BE level was significantly lower (−4.7 ± 4.0 vs. −3.3 ± 4.3; p=0.02) in patients with CKD progression. The patients in group 1 (n: 130) (Be<−2.5) revealed more CKD progression (%53 vs. %32; p=0.002), and RRT requirement (%35 vs. %15; p=0.001). Baseline BE <−2.5 (odds ratio, 0.38; 95% CI, 0.16 to 0.91; p<0.05) and baseline GFR (odds ratio, 0.94; 95% CI, 0.90 to 0.97; p<0.001) were independently related to RRT requirement. Delta BE was independently associated with mortality (odds ratio, 0.90; 95% CI, 0.85–0.96; p<0.01).ConclusionsLow BE levels were associated with CKD progression and RRT requirement. BE change is associated with mortality during the follow-up of those patients.

Serum Magnesium, Blood Pressure, and Risk of Hypertension and Chronic Kidney Disease Progression in the CRIC Study

Hypertension ◽  
2021 ◽  
Author(s):  
Simon Correa ◽  
Xavier E. Guerra-Torres ◽  
Sushrut S. Waikar ◽  
Finnian R. Mc Causland
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Disease Progression ◽  
Lower Risk ◽  
Serum Magnesium ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Ckd Progression ◽  
Baseline Serum

Magnesium is involved in the regulation of blood pressure (BP). Abnormalities in serum magnesium are common in chronic kidney disease (CKD), yet its association with the development of hypertension and CKD progression in patients with CKD is unclear. We analyzed data from 3866 participants from the CRIC Study (Chronic Renal Insufficiency Cohort). Linear regression assessed the association of serum magnesium with baseline systolic BP (SBP) and diastolic BP (DBP). Logistic regression explored the association of serum magnesium with various definitions of hypertension. Cox proportional hazards models explored assessed the risk of incident hypertension and CKD progression. Mean serum magnesium was 2.0 mEq/L (±0.3 mEq/L). Higher magnesium was associated with lower SBP (−3.4 mm Hg [95% CI, −5.8 to −1.0 per 1 mEq/L]) and lower DBP (−2.9 mm Hg [95% CI, −4.3 to −1.5 per 1 mEq/L]). Higher magnesium was associated with a lower risk of American Heart Association–defined hypertension (SBP≥130 mm Hg or DBP≥80 mm Hg) at baseline (adjusted hazard ratio, 0.65 [95% CI, 0.49–0.86 per 1 mEq/L]), a lower risk of suboptimally controlled BP (SBP≥120 mm Hg or DBP≥80 mm Hg; adjusted odds ratio, 0.58 [95% CI, 0.43–0.78 per 1 mEq/L]). In time-to-event analyses, higher baseline serum magnesium was associated with a nominally lower risk of incident CRIC-defined hypertension (adjusted hazard ratio, 0.77 [95% CI, 0.46–1.31 per 1 mEq/L]). Higher magnesium was associated with a significantly lower risk of CKD progression (adjusted hazard ratio, 0.68 [95% CI, 0.54–0.86 per 1 mEq/L]). In patients with CKD, higher serum magnesium is associated with lower SBP and DBP, and with a lower risk of hypertension and CKD progression. In patients with CKD, whether magnesium supplementation could optimize BP control and prevent disease progression deserves further investigation.

scholarly journals Correlation of electrophoretic urine protein banding patterns with severity of renal damage in dogs with proteinuric chronic kidney disease

2018 ◽  
Vol 47 (3) ◽  
pp. 425-434 ◽  
Author(s):  
Jessica A. Hokamp ◽  
Sidney A. Leidy ◽  
Irina Gaynanova ◽  
Rachel E. Cianciolo ◽  
Mary B. Nabity
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Damage ◽  
Urine Protein ◽  
Banding Patterns

AT1 blockade during lactation as a model of chronic nephropathy: mechanisms of renal injury

2008 ◽  
Vol 294 (6) ◽  
pp. F1345-F1353 ◽  
Author(s):  
Flavia Gomes Machado ◽  
Elizabete Pereira Barros Poppi ◽  
Camilla Fanelli ◽  
Denise Maria Avancini Costa Malheiros ◽  
Roberto Zatz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Injury ◽  
Time Course ◽  
Structural Changes ◽  
Adult Life ◽  
Renin Angiotensin System ◽  
Urine Osmolality ◽  
Systemic Hypertension ◽  
Advanced Stages

Suppression of the renin-angiotensin system during lactation causes irreversible renal structural changes. In this study we investigated 1) the time course and the mechanisms underlying the chronic kidney disease caused by administration of the AT1 receptor blocker losartan during lactation, and 2) whether this untoward effect can be used to engender a new model of chronic kidney disease. Male Munich-Wistar pups were divided into two groups: C, whose mothers were untreated, and LLact, whose mothers received oral losartan (250 mg·kg−1·day−1) during the first 20 days after delivery. At 3 mo of life, both nephron number and the glomerular filtration rate were reduced in LLact rats, whereas glomerular pressure was elevated. Unselective proteinuria and decreased expression of the zonula occludens-1 protein were also observed, along with modest glomerulosclerosis, significant interstitial expansion and inflammation, and wide glomerular volume variation, with a stable subpopulation of exceedingly small glomeruli. In addition, the urine osmolality was persistently lower in LLact rats. At 10 mo of age, LLact rats exhibited systemic hypertension, heavy albuminuria, substantial glomerulosclerosis, severe renal interstitial expansion and inflammation, and creatinine retention. Conclusions are that 1) oral losartan during lactation can be used as a simple and easily reproducible model of chronic kidney disease in adult life, associated with low mortality and no arterial hypertension until advanced stages; and 2) the mechanisms involved in the progression of renal injury in this model include glomerular hypertension, glomerular hypertrophy, podocyte injury, and interstitial inflammation.

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