scholarly journals Mitochondrial Bioenergetic and Proteomic Phenotyping Reveals Organ-Specific Consequences of Chronic Kidney Disease in Mice

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3282
Author(s):  
Trace Thome ◽  
Madeline D. Coleman ◽  
Terence E. Ryan
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Renal Tissue ◽  
Tissue Specific ◽  
Organ Specific ◽  
Proteomic Analyses ◽  
Reduced Kidney Function ◽  
Specific Impact

Chronic kidney disease (CKD) results in reduced kidney function, uremia, and accumulation of uremic metabolites. Mitochondrial alterations have been suggested to play a role in the disease pathology within various tissues. The purpose of this study was to perform a comprehensive bioenergetic and proteomic phenotyping of mitochondria from skeletal muscle (SkM), cardiac muscle (CM), and renal tissue from mice with CKD. The 5-month-old C57BL/6J male mice were fed a casein control or adenine-supplemented diet for 6 months. CKD was confirmed by blood urea nitrogen. A mitochondrial diagnostic workflow was employed to examine respiratory function, membrane and redox potential, reactive oxygen species production, and maximal activities of matrix dehydrogenases and electron transport system (ETS) protein complexes. Additionally, tandem-mass-tag-assisted proteomic analyses were performed to uncover possible differences in mitochondrial protein abundance. CKD negatively impacted mitochondrial energy transduction (all p < 0.05) in SkM, CM, and renal mitochondria, when assessed at physiologically relevant cellular energy demands (ΔGATP) and revealed the tissue-specific impact of CKD on mitochondrial health. Proteomic analyses indicated significant abundance changes in CM and renal mitochondria (115 and 164 proteins, p < 0.05), but no differences in SkM. Taken together, these findings reveal the tissue-specific impact of chronic renal insufficiency on mitochondrial health.

scholarly journals Altered Emotional Phenotypes in Chronic Kidney Disease Following 5/6 Nephrectomy

2021 ◽  
Vol 11 (7) ◽  
pp. 882
Author(s):  
Yeon Hee Yu ◽  
Seong-Wook Kim ◽  
Dae-Kyoon Park ◽  
Ho-Yeon Song ◽  
Duk-Soo Kim ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Local Field ◽  
Smooth Muscle Actin ◽  
Local Field Potentials ◽  
Renal Tissue ◽  
Field Potentials ◽  
Wild Type ◽  
Sprague Dawley ◽  
Rat Models

Increased prevalence of chronic kidney disease (CKD) and neurological disorders including cerebrovascular disease, cognitive impairment, peripheral neuropathy, and dysfunction of central nervous system have been reported during the natural history of CKD. Psychological distress and depression are serious concerns in patients with CKD. However, the relevance of CKD due to decline in renal function and the pathophysiology of emotional deterioration is not clear. Male Sprague Dawley rats were divided into three groups: sham control, 5/6 nephrectomy at 4 weeks, and 5/6 nephrectomy at 10 weeks. Behavior tests, local field potentials, and histology and laboratory tests were conducted and investigated. We provided direct evidence showing that CKD rat models exhibited anxiogenic behaviors and depression-like phenotypes, along with altered hippocampal neural oscillations at 1–12 Hz. We generated CKD rat models by performing 5/6 nephrectomy, and identified higher level of serum creatinine and blood urea nitrogen (BUN) in CKD rats than in wild-type, depending on time. In addition, the level of α-smooth muscle actin (α-SMA) and collagen I for renal tissue was markedly elevated, with worsening fibrosis due to renal failures. The level of anxiety and depression-like behaviors increased in the 10-week CKD rat models compared with the 4-week rat models. In the recording of local field potentials, the power of delta (1–4 Hz), theta (4–7 Hz), and alpha rhythm (7–12 Hz) was significantly increased in the hippocampus of CKD rats compared with wild-type rats. Together, our findings indicated that anxiogenic behaviors and depression can be induced by CKD, and these abnormal symptoms can be worsened as the onset of CKD was prolonged. In conclusion, our results show that the hippocampus is vulnerable to uremia.

scholarly journals Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp

2017 ◽  
Vol 312 (3) ◽  
pp. E175-E182 ◽  
Author(s):  
Iram Ahmad ◽  
Leila R. Zelnick ◽  
Nicole R. Robinson ◽  
Adriana M. Hung ◽  
Bryan Kestenbaum ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Insulin Sensitivity ◽  
Kidney Disease ◽  
Oral Glucose ◽  
Cross Sectional ◽  
Euglycemic Clamp ◽  
Insulin Kinetics ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Sensitivity Indices ◽  
Organ Specific

Insulin sensitivity can be measured by procedures such as the hyperinsulinemic euglycemic clamp or by using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. In a cross-sectional study of 59 subjects with nondiabetic CKD [estimated glomerular filtration rate: (GFR) <60 ml·min−1·1.73 m2] and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SIclamp), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SIclamp using descriptive statistics, graphical analyses, correlation coefficients, and linear regression. Mean age was 62.6 yr; 48% of the participants were female, and 77% were Caucasian. Insulin sensitivity indices were 8–38% lower in participants with vs. without CKD and 13–59% lower in obese compared with nonobese participants. Correlations of surrogate indices with SIclamp did not differ significantly by CKD or obesity status. Adjusting for SIclamp in addition to demographic factors, Matsuda index was 15% lower in participants with vs. without CKD ( P = 0.09) and 36% lower in participants with vs. without obesity ( P = 0.0001), whereas 1/HOMA-IR was 23% lower in participants with vs. without CKD ( P = 0.02) and 46% lower in participants with vs. without obesity ( P < 0.0001). We conclude that CKD and obesity do not significantly alter correlations of surrogate insulin sensitivity indices with SIclamp, but they do bias surrogate measurements of insulin sensitivity toward lower values. This bias may be due to differences in insulin kinetics or organ-specific responses to insulin.

scholarly journals Pharmacokinetics and Pharmacodynamics of the Combination of Rhein and Curcumin in the Treatment of Chronic Kidney Disease in Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoying He ◽  
Guowei Li ◽  
Yuanyuan Chen ◽  
Qiming Xiao ◽  
Xinwei Yu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Molecular Docking ◽  
Kidney Disease ◽  
Interaction Mechanism ◽  
Ultra Performance Liquid Chromatography ◽  
Renal Tissue ◽  
Combination Group ◽  
Sprague Dawley ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Sd Rats

Objectives: The interaction between the components of traditional Chinese medicine (TCM) is an important basis for their synergy. Rhein and curcumin exert various pharmacological activities, including anti-tumour, anti-inflammatory, antioxidant, anti-fibrosis and renoprotective effects. However, no investigation has reported the synergistic anti-fibrosis effect yet. This study aims at determine the pharmacokinetics and pharmacodynamics of the combination of rhein and curcumin in the treatment for chronic kidney disease in rats.Design: Fifty two male Sprague-Dawley (SD) rats were randomly divided into rhein group, curcumin group and their combination group for pharmacodynamics studies. HE and Masson staining was conducted to observe the changes of renal morphology. Kits were used to detect the level of urea nitrogen (BUN) and creatinine (Scr). For pharmacokinetic study, 36 SD rats were randomly divided into rhein group, curcumin group and a combination group, the content of rhein and curcumin in plasma and renal tissue was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In additon, molecular docking method and cell experiments was used to disclose the interaction mechanism between curcumin and rhein.Results: The pharmacodynamic results showed that the degree of renal fibrosis was improved obviously by co-administration rhein and curcumin. Meanwhile, compared to single administration, the Cmax and AUC of rhein and curcumin in plasma and renal tissue were enhanced significantly after co-administration. Moreover, the result of molecular docking and cell experiments showed that both two compounds could interact with P-gp, CYP2C9 and CYP2C19.Conclusion: Together, these findings demonstrated that rhein and curcumin had a synergistic effect in ameliorateing chonic kidney disease, providing an important explanation on the synergistic mechanism of curcumin and rhein from a pharmacokinetic viewpoint.

scholarly journals Chronic exposure to hypoxia attenuates renal injury and innate immunity activation in the remnant kidney model

2019 ◽  
Vol 317 (5) ◽  
pp. F1285-F1292 ◽  
Author(s):  
Lisienny Campoli Tono Rempel ◽  
Viviane Dias Faustino ◽  
Orestes Foresto-Neto ◽  
Camilla Fanelli ◽  
Simone Costa Alarcon Arias ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Innate Immunity ◽  
Kidney Disease ◽  
Renal Injury ◽  
Cortical Area ◽  
Prolonged Exposure ◽  
Capillary Density ◽  
Renal Tissue ◽  
Peritubular Capillary

Hypoxia is thought to influence the pathogenesis of chronic kidney disease, but direct evidence that prolonged exposure to tissue hypoxia initiates or aggravates chronic kidney disease is lacking. We tested this hypothesis by chronically exposing normal rats and rats with 5/6 nephrectomy (Nx) to hypoxia. In addition, we investigated whether such effect of hypoxia would involve activation of innate immunity. Adult male Munich-Wistar rats underwent Nx ( n = 54) or sham surgery (sham; n = 52). Twenty-six sham rats and 26 Nx rats remained in normoxia, whereas 26 sham rats and 28 Nx rats were kept in a normobaric hypoxia chamber (12% O2) for 8 wk. Hypoxia was confirmed by immunohistochemistry for pimonidazole. Hypoxia was confined to the medullary area in sham + normoxia rats and spread to the cortical area in sham + hypoxia rats, without changing the peritubular capillary density. Exposure to hypoxia promoted no renal injury or elevation of the content of IL-1β or Toll-like receptor 4 in sham rats. In Nx, hypoxia also extended to the cortical area without ameliorating the peritubular capillary rarefaction but, unexpectedly, attenuated hypertension, inflammation, innate immunity activation, renal injury, and oxidative stress. The present study, in disagreement with current concepts, shows evidence that hypoxia exerts a renoprotective effect in the Nx model instead of acting as a factor of renal injury. The mechanisms for this unexpected beneficial effect are unclear and may involve NF-κB inhibition, amelioration of oxidative stress, and limitation of angiotensin II production by the renal tissue.

scholarly journals Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study

2020 ◽  
Author(s):  
Ulla T Schultheiss ◽  
Inga Steinbrenner ◽  
Matthias Nauck ◽  
Markus P Schneider ◽  
Fruzsina Kotsis ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Thyroid Function ◽  
Positive Association ◽  
Inverse Association ◽  
All Cause Mortality ◽  
Disease Study ◽  
Reduced Kidney Function

Abstract Background Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function. Methods Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status. Results Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (Nevents = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65–0.82; Nevents = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint. Conclusions Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.

scholarly journals Clinical Epidemiology of Reduced Kidney Function among Elderly Male Fishing and Agricultural Population in Taipei, Taiwan

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Chi-Mei Kuo ◽  
Wu-Hsiung Chien ◽  
Hsi-Che Shen ◽  
Yi-Chun Hu ◽  
Yu-Fen Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Associated Factors ◽  
Estimated Glomerular Filtration Rate ◽  
Clinical Epidemiology ◽  
The Elderly ◽  
Multiple Logistic Regression ◽  
Clinical Factors ◽  
Elderly Male ◽  
Reduced Kidney Function

Purpose. To quantify the prevalence of and associated factors for chronic kidney disease (CKD) among male elderly fishing and agricultural population in Taipei, Taiwan.Methods. Subjects (n=2,766) aged 65 years and over voluntarily admitted to a teaching hospital for a physical checkup were collected in 2010. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2.Results. Among these subjects, the over prevalence of chronic kidney disease was 13.6% (95% CI: 12.3–14.9%). The age-specific prevalence of CKD in 65–74 years, 75–84 years, and ≥85 years was 8.2%, 19.1%, and 27.0%, respectively. From the multiple logistic regression, age (OR = 1.05, 95% CI: 1.02–1.09), hyperuricemia (OR = 2.94, 95% CI: 1.90–3.78), central obesity (OR = 1.17, 95% CI: 1.02–1.56), hyperglycemia (OR = 1.23, 95% CI: 1.11–1.67), hypertriglyceridemia (OR = 1.25, 95% CI: 1.08–1.66), and lower HDL-C (OR = 1.61, 95% CI: 1.23–1.92) were statistically significantly related to CKD. The presence of metabolic components (one or two versus none, OR = 1.10, 95% CI: 1.04–1.25; three or more versus none, OR = 2.12, 95% CI: 1.86–2.78) also appeared to be statistically significantly related to CKD after adjustment for other independent factors.Conclusion. Several clinical factors independently affect the development of CKD in the elderly male fishing and agricultural population.

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