scholarly journals Renal oxygenation during the early stages of adenine-induced chronic kidney disease

2019 ◽  
Vol 317 (5) ◽  
pp. F1189-F1200 ◽  
Author(s):  
Md Mahbub Ullah ◽  
Connie P. C. Ow ◽  
Lucinda M. Hilliard Krause ◽  
Roger G. Evans
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Hypoxia Inducible Factor ◽  
Early Event ◽  
Pathological Feature ◽  
Sprague Dawley ◽  
Creatinine Concentration ◽  
Medullary Tissue ◽  
Clark Electrode

To assess whether renal hypoxia is an early event in adenine-induced chronic kidney disease, adenine (100 mg) or its vehicle was administered to male Sprague-Dawley rats by daily oral gavage for 7 days. Kidney oxygenation was assessed by 1) blood oximetry and Clark electrode in thiobutabarbital-anesthetized rats, 2) radiotelemetry in unanesthetized rats, and 3) expression of hypoxia-inducible factor (HIF)-1α and HIF-2α protein. After 7 days of treatment, under anesthesia, renal O2 delivery was 51% less, whereas renal O2 consumption was 65% less, in adenine-treated rats than in vehicle-treated rats. Tissue Po2 measured by Clark electrode was similar in the renal cortex but 44% less in the medulla of adenine-treated rats than in that of vehicle-treated rats. In contrast, in unanesthetized rats, both cortical and medullary tissue Po2 measured by radiotelemetry remained stable across 7 days of adenine treatment. Notably, anesthesia and laparotomy led to greater reductions in medullary tissue Po2 measured by radiotelemetry in rats treated with adenine (37%) than in vehicle-treated rats (16%), possibly explaining differences between our observations with Clark electrodes and radiotelemetry. Renal expression of HIF-1α was less after 7 days of adenine treatment than after vehicle treatment, whereas expression of HIF-2α did not differ significantly between the two groups. Renal dysfunction was evident after 7 days of adenine treatment, with glomerular filtration rate 65% less and serum creatinine concentration 183% greater in adenine-treated rats than in vehicle-treated rats. Renal cortical tissue hypoxia may not precede renal dysfunction in adenine-induced chronic kidney disease and so may not be an early pathological feature in this model.

scholarly journals A dual blocker of endothelin A/B receptors mitigates hypertension but not renal dysfunction in a rat model of chronic kidney disease and sleep apnea

2019 ◽  
Vol 316 (5) ◽  
pp. F1041-F1052 ◽  
Author(s):  
Humberto Morales-Loredo ◽  
David Jones ◽  
Adelaeda Barrera ◽  
Perenkita J. Mendiola ◽  
Joshua Garcia ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Sleep Apnea ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Rat Model ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Obstructive Sleep ◽  
End Stage

Obstructive sleep apnea is characterized by recurrent episodes of pharyngeal collapse during sleep, resulting in intermittent hypoxia (IH), and is associated with a high incidence of hypertension and accelerated renal failure. In rodents, endothelin (ET)-1 contributes to IH-induced hypertension, and ET-1 levels inversely correlate with glomerular filtration rate in patients with end-stage chronic kidney disease (CKD). Therefore, we hypothesized that a dual ET receptor antagonist, macitentan (Actelion Pharmaceuticals), will attenuate and reverse hypertension and renal dysfunction in a rat model of combined IH and CKD. Male Sprague-Dawley rats received one of three diets (control, 0.2% adenine, and 0.2% adenine + 30 mg·kg−1·day−1macitentan) for 2 wk followed by 2 wk of recovery diet. Rats were then exposed for 4 wk to air or IH (20 short exposures/h to 5% O2-5% CO27 h/day during sleep). Macitentan prevented the increases in mean arterial blood pressure caused by CKD, IH, and the combination of CKD + IH. However, macitentan did not improve kidney function, fibrosis, and inflammation. After CKD was established, rats were exposed to air or IH for 2 wk, and macitentan feeding continued for 2 more wk. Macitentan reversed the hypertension in IH, CKD, and CKD + IH groups without improving renal function. Our data suggest that macitentan could be an effective antihypertensive in patients with CKD and irreversible kidney damage as a way to protect the heart, brain, and eyes from elevated arterial pressure, but it does not reverse toxin-induced tubule atrophy.

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 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.

Histomorphometry of Feline Chronic Kidney Disease and Correlation With Markers of Renal Dysfunction

2012 ◽  
Vol 50 (1) ◽  
pp. 147-155 ◽  
Author(s):  
S. Chakrabarti ◽  
H. M. Syme ◽  
C. A. Brown ◽  
J. Elliott
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Image Analysis ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Interstitial Fibrosis ◽  
Glomerular Hypertrophy ◽  
Renal Lesions ◽  
Postmortem Examinations

Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression ( P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis.

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 Nephroprotective strategy in the treatment of hypertension as a modern general medical problem

2018 ◽  
pp. 107-118 ◽  
Author(s):  
V. I. Podzolkov ◽  
A. E. Bragina ◽  
T. I. Ishina ◽  
L. V. Bragina ◽  
L. V. Vasilyeva
Keyword(s):  
Chronic Kidney Disease ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Medical Problem ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
High Prevalence ◽  
Advanced Stages ◽  
Receptor Blockers

The current population is characterized by a high prevalence of risk factors for the development of chronic kidney disease: hypertension, diabetes, obesity, metabolic syndrome, physical inactivity, smoking. The development of severe complications and a close connection with potentially fatal cardiovascular disorders make this disease a socially and economically significant problem. Treatment of chronic kidney disease in advanced stages belong to nephrologist duties. However, the success of preventive interventions depends on the time of their onset, which makes it relevant to identify the disease. The use of nephroprotective approaches by physicians of different specialties (general practitioners, cardiologists, gerontologists, nephrologists, endocrinologists) can significantly improve the prognosis of both those at risk of developing renal dysfunction and the existing disease. The review presents data on the clinical and laboratory efficacy of angiotensin-renin blocker use, as well as the combination of angiotensin II receptor blockers with calcium antagonists. Using the combination of the angiotensin II receptor blocker irbesartan and amlodipine as an example, we demonstrated the possibilities of nephroprotective therapy in patients with renal dysfunction.

scholarly journals Renal dysfunction indicative of outcomes in hospitalized patients with takotsubo syndrome

2017 ◽  
Vol 7 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Kaoru Ando ◽  
Hiroyasu Sukekawa ◽  
Aoi Takahata ◽  
Yusuke Kobari ◽  
Hayato Tsuchiya ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Confidence Interval ◽  
Renal Dysfunction ◽  
Left Ventricular ◽  
Hazard Ratio ◽  
Hospitalized Patients ◽  
Rank Test ◽  
Takotsubo Syndrome ◽  
Pump Failure

Background: Left ventricular dysfunction as part of takotsubo syndrome is reversible, and the long-term prognosis appears favorable. However, life-threatening complications are not uncommon during the acute phase, and it remains unclear whether renal dysfunction is a factor in complications suffered by hospitalized patients with takotsubo syndrome. The present study was conducted to investigate the implications of renal dysfunction in this setting. Methods: Data from 61 consecutive patients (male, 21; female, 40) diagnosed with takotsubo syndrome at our hospital between years 2010 and 2016 were evaluated retrospectively. In-hospital complications by definition were all-cause deaths and severe pump failure (Killip class ≥III). Results: Overall, 30 patients (49%) developed renal dysfunction. In the 32 patients (52%) who suffered in-hospital complications (mortality, 10; severe pump failure, 22), estimated glomerular filtration rate (eGFR) was significantly lower by comparison (51.3±29.8 vs. 69.5±29.0; p=0.019). Low eGFR (<30 ml/min per 1.73m2) proved independently predictive of in-hospital complications (hazard ratio =2.84, 95% confidence interval: 1.20–6.69) in multivariate Cox hazard analysis, also showing a significant association with peak event rate of Kaplan–Meier curve (log-rank test, p=0.0073). Similarly, patients with chronic kidney disease were at significantly greater risk of in-hospital complications (hazard ratio=2.49, 95% confidence interval: 1.01–5.98), relative to non-compromised counterparts (eGFR >60 ml/min per 1.73m2). Conclusion: Renal dysfunction is a simple but useful means of predicting complications in hospitalized patients with takotsubo syndrome, especially those with chronic kidney disease.

scholarly journals Dickkopf-3 in the prediction of contrast media induced acute kidney injury

2020 ◽  
Author(s):  
Felix S. Seibert ◽  
Anja Heringhaus ◽  
Nikolaos Pagonas ◽  
Benjamin Rohn ◽  
Frederic Bauer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Coronary Angiography ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Acute Kidney Injury Network ◽  
Creatinine Ratio ◽  
Creatinine Concentration

Abstract Background Dickkopf-3 (DKK3) has recently been discovered as a urinary biomarker for the prediction of acute kidney injury (AKI) after cardiac surgery. This finding needs to be confirmed for AKI in other clinical settings. The present study investigates whether DKK3 can predict contrast-induced AKI (CI-AKI). Methods We performed a prospective study in 490 patients undergoing coronary angiography. Primary endpoint was an increase in serum creatinine concentration ≥ 0.3 mg/dl within 72 h after the procedure. DKK3 was assessed < 24 h before coronary angiography. Predictive accuracy was assessed by receiver operating characteristic (ROC) curves. Results CI-AKI was observed in 30 (6.1%) patients, of whom 27 corresponded to stage I and 3 to stage II according to the Acute Kidney Injury Network (AKIN) criteria. Subjects who developed CI-AKI had a 3.8-fold higher urinary DKK3/creatinine ratio than those without CI-AKI (7.5 pg/mg [interquartile range [IQR] 1.2–1392.0] vs. 2.0 pg/mg [IQR 0.9–174.0]; p = 0.047). ROC analysis revealed an area under the curve (AUC) of 0.61. Among subjects without clinically overt chronic kidney disease (estimated glomerular filtration rate [eGFR] > 60 ml/min, urinary albumin creatinine ratio < 30 mg/g), the DKK3/creatinine ratio was 5.4-fold higher in those with subsequent CI-AKI (7.5 pg/mg [IQR 0.9–590.1] vs. 1.38 pg/mg [IQR 0.8–51.0]; p = 0.007; AUC 0.62). Coronary angiography was associated with a 43 times increase in the urinary DKK3/creatinine ratio. Conclusions Urinary DKK3 is an independent predictor of CI-AKI even in the absence of overt chronic kidney disease (CKD). The study thereby expands the findings on DKK3 in the prediction of postoperative loss of kidney function to other entities of AKI. Graphic abstract

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