scholarly journals Development of a Model of Chronic Kidney Disease in the C57BL/6 Mouse with Properties of Progressive Human CKD

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Zahraa Mohammed-Ali ◽  
Gaile L. Cruz ◽  
Chao Lu ◽  
Rachel E. Carlisle ◽  
Kaitlyn E. Werner ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Animal Model ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Treatment Strategies ◽  
Premenopausal Women ◽  
Cell Loss ◽  
Tubular Epithelial Cell ◽  
Common Features ◽  
Stage Renal Disease

Chronic kidney disease (CKD) is a major healthcare problem with increasing prevalence in the population. CKD leads to end stage renal disease and increases the risk of cardiovascular disease. As such, it is important to study the mechanisms underlying CKD progression. To this end, an animal model was developed to allow the testing of new treatment strategies or molecular targets for CKD prevention. Many underlying risk factors result in CKD but the disease itself has common features, including renal interstitial fibrosis, tubular epithelial cell loss through apoptosis, glomerular damage, and renal inflammation. Further, CKD shows differences in prevalence between the genders with premenopausal women being relatively resistant to CKD. We sought to develop and characterize an animal model with these common features of human CKD in the C57BL/6 mouse. Mice of this genetic background have been used to produce transgenic strains that are commercially available. Thus, a CKD model in this strain would allow the testing of the effects of numerous genes on the severity or progression of CKD with minimal cost. This paper describes such a mouse model of CKD utilizing angiotensin II and deoxycorticosterone acetate as inducers.

scholarly journals Renoprotective Effects of ETA Receptor Antagonists Therapy in Experimental Non-Diabetic Chronic Kidney Disease: Is There Still Hope for the Future?

2018 ◽  
pp. S55-S67 ◽  
Author(s):  
I. VANĚČKOVÁ ◽  
S. HOJNÁ ◽  
M. KADLECOVÁ ◽  
Z. VERNEROVÁ ◽  
L. KOPKAN ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cell Injury ◽  
Interstitial Fibrosis ◽  
Experimental Studies ◽  
Tubular Atrophy ◽  
Eta Receptor ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ETA) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ETA receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ETA blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ETA antagonists, at least under certain pathological conditions.

Clinicopathological predictors for progression of chronic kidney disease in nephrosclerosis: a biopsy-based cohort study

2018 ◽  
Vol 34 (7) ◽  
pp. 1182-1188 ◽  
Author(s):  
Masayuki Yamanouchi ◽  
Junichi Hoshino ◽  
Yoshifumi Ubara ◽  
Kenmei Takaichi ◽  
Keiichi Kinowaki ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Albumin ◽  
Hemoglobin A1c ◽  
Interstitial Fibrosis ◽  
Information Criterion ◽  
Ckd Progression ◽  
Tubular Atrophy ◽  
Net Reclassification Improvement ◽  
Stage Renal Disease

Abstract Background Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. Methods We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by  ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell’s C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. Results During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35–0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54–0.94), eGFR (SHR 0.98; 95% CI 0.97–0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08–1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00–1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20–1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. Conclusions The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.

scholarly journals Investigation of the Impact of Endodontic Therapy on Survival among Dialysis Patients in Taiwan: A Nationwide Population-Based Cohort Study

2021 ◽  
Vol 18 (1) ◽  
pp. 326
Author(s):  
Chih-Chien Chiu ◽  
Ya-Chieh Chang ◽  
Ren-Yeong Huang ◽  
Jenq-Shyong Chan ◽  
Chi-Hsiang Chung ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Root Canal ◽  
Dialysis Patients ◽  
Root Canal Therapy ◽  
Risk Of Death ◽  
Stage Renal Disease ◽  
End Stage

Objectives Dental problems occur widely in patients with chronic kidney disease (CKD) and may increase comorbidities. Root canal therapy (RCT) is a common procedure for advanced decayed caries with pulp inflammation and root canals. However, end-stage renal disease (ESRD) patients are considered to have a higher risk of potentially life-threatening infections after treatment and might fail to receive satisfactory dental care such as RCT. We investigated whether appropriate intervention for dental problems had a potential impact among dialysis patients. Design Men and women who began maintenance dialysis (hemodialysis or peritoneal dialysis) between January 1, 2000, and December 31, 2015, in Taiwan (total 12,454 patients) were enrolled in this study. Participants were followed up from the first reported dialysis date to the date of death or end of dialysis by December 31, 2015. Setting Data collection was conducted in Taiwan. Results A total of 2633 and 9821 patients were classified into the RCT and non-RCT groups, respectively. From the data of Taiwan’s National Health Insurance, a total of 5,092,734 teeth received RCT from 2000 to 2015. Then, a total of 12,454 patients were followed within the 16 years, and 4030 patients passed away. The results showed that members of the non-RCT group (34.93%) had a higher mortality rate than those of the RCT group (22.79%; p = 0.001). The multivariate-adjusted hazard ratio for the risk of death was 0.69 (RCT vs. non-RCT; p = 0.001). Conclusions This study suggested that patients who had received RCT had a relatively lower risk of death among dialysis patients. Infectious diseases had a significant role in mortality among dialysis patients with non-RCT. Appropriate interventions for dental problems may increase survival among dialysis patients. Abbreviations: CKD = chronic kidney disease, ESRD = end-stage renal disease, RCT = root canal therapy.

scholarly journals The Nephroprotective Properties of Extracellular Vesicles in Experimental Models of Chronic Kidney Disease: a Systematic Review

2021 ◽  
Author(s):  
Natalia Nowak ◽  
Masayuki Yamanouchi ◽  
Eiichiro Satake
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Cell Damage ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Extracellular Vesicle ◽  
Experimental Models ◽  
Preclinical Research

AbstractExtracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD. Graphical Abstract

scholarly journals Delayed Exercise Training Improves Obesity-Induced Chronic Kidney Disease by Activating AMPK Pathway in High-Fat Diet-Fed Mice

2020 ◽  
Vol 22 (1) ◽  
pp. 350
Author(s):  
Florian Juszczak ◽  
Maud Vlassembrouck ◽  
Olivia Botton ◽  
Thomas Zwakhals ◽  
Morgane Decarnoncle ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Exercise Training ◽  
High Fat Diet ◽  
Interstitial Fibrosis ◽  
Calorie Intake ◽  
Acid Oxidation ◽  
Obese Mice ◽  
High Fat ◽  
Ampk Pathway

Exercise training is now recognized as an interesting therapeutic strategy in managing obesity and its related disorders. However, there is still a lack of knowledge about its impact on obesity-induced chronic kidney disease (CKD). Here, we investigated the effects of a delayed protocol of endurance exercise training (EET) as well as the underlying mechanism in obese mice presenting CKD. Mice fed a high-fat diet (HFD) or a low-fat diet (LFD) for 12 weeks were subsequently submitted to an 8-weeks EET protocol. Delayed treatment with EET in obese mice prevented body weight gain associated with a reduced calorie intake. EET intervention counteracted obesity-related disorders including glucose intolerance, insulin resistance, dyslipidaemia and hepatic steatosis. Moreover, our data demonstrated for the first time the beneficial effects of EET on obesity-induced CKD as evidenced by an improvement of obesity-related glomerulopathy, tubulo-interstitial fibrosis, inflammation and oxidative stress. EET also prevented renal lipid depositions in the proximal tubule. These results were associated with an improvement of the AMPK pathway by EET in renal tissue. AMPK-mediated phosphorylation of ACC and ULK-1 were particularly enhanced leading to increased fatty acid oxidation and autophagy improvement with EET in obese mice.

scholarly journals MicroRNA-451 as an Early Predictor of Chronic Kidney Disease in Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Mostafa Abdelsalam ◽  
A. M. Wahab ◽  
Maysaa El Sayed Zaki ◽  
Mohamad Motawea
Keyword(s):  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Early Diagnosis ◽  
Serum Creatinine ◽  
High Sensitivity ◽  
Urinary Albumin ◽  
Significant Difference ◽  
Plasma Microrna ◽  
Stage Renal Disease

Background. Diabetes mellitus is the leading cause of end-stage renal disease worldwide. Microalbuminuria is the cornerstone for the diagnosis of diabetic nephropathy. However, it is an inadequate marker for early diagnosis. MicroRNAs are not only new and promising markers for early diagnosis but also, but they may also play a role in the prevention of disease progression. Methods. This study included ninety patients with type 2 DM in addition to 30 control subjects. MicroRNA-451 expression in blood and plasma using real-time PCR was evaluated in addition to the classic diabetic nephropathy markers (serum creatinine, urinary albumin, and eGFR). Results. There was a significant difference between the studied groups versus control regarding serum creatinine, eGFR, urinary, and plasma microRNA-451 with p=0.0001. Patients with eGFR 60 ml/min/1.73 m2 showed a significantly higher plasma microRNA-451 (29.6 ± 1.6) and significantly lower urinary microRNA-451 (21 ± 0.9) in comparison to patients with eGFR >60 ml/min/1.73 m2 and p=0.0001. eGFR showed a positive correlation with urinary microRNA-451 and negative correlation with both plasma microRNA-451 and urinary albumin. Both plasma and urinary microRNA-451 are highly sensitive and specific markers for chronicity in diabetic nephropathy patients with sensitivity of 90.9% and 95.5% and specificity of 67.6% and 95.6%, respectively. Conclusion. MicroRNA-451 is a promising early biomarker for chronic kidney disease in diabetic nephropathy with high sensitivity and specificity.

Serum Sodium Levels and Patient Outcomes in an Ambulatory Clinic-Based Chronic Kidney Disease Cohort

2015 ◽  
Vol 41 (3) ◽  
pp. 200-209 ◽  
Author(s):  
Sang-Woong Han ◽  
Anca Tilea ◽  
Brenda W. Gillespie ◽  
Fredric O. Finkelstein ◽  
Margaret A. Kiser ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Patient Outcomes ◽  
Serum Sodium ◽  
Risk Of Mortality ◽  
Ambulatory Patients ◽  
Lower Egfr ◽  
Stage Renal Disease ◽  
End Stage ◽  
Improve Patient

Background: Chronic kidney disease (CKD) patients are prone to both hypo- and hypernatremia. Little has been published on the epidemiology of hypo- and hypernatremia in ambulatory patients with non-dialysis CKD. Methods: Data collected in two contemporaneous CKD cohort studies, the Renal Research Institute (RRI)-CKD study (n = 834) and the Study of Treatment of Renal Insufficiency: Data and Evaluation (STRIDE) (n = 1,348) were combined and analyzed to study the association between serum sodium (Na+) and clinical outcomes. Results: Baseline estimated glomerular filtration rate (eGFR) and Na+ were 26 ± 11 ml/min/1.73 m2 and 140.2 ± 3.4 mEq/l, respectively. The prevalence of Na+ ≤135 mEq/l and ≥144 mEq/l was 6 and 16%, respectively. Higher baseline Na+ was significantly associated with male sex, older age, systolic blood pressure, BMI, serum albumin, presence of heart failure, and lower eGFR. The risk of end-stage renal disease (ESRD) was marginally significantly higher among patients with Na+ ≤135 mEq/l, compared with 140< Na+ <144 mEq/l (referent), in time-dependent models (adjusted hazard ratio, HR = 1.52, p = 0.06). Mortality risk was significantly greater at 135< Na+ ≤140 mEq/l (adjusted HR = 1.68, p = 0.02) and Na+ ≥144 mEq/l (adjusted HR = 2.01, p = 0.01). Conclusion: CKD patients with Na+ ≤135 mEq/l were at a higher risk for progression to ESRD, whereas both lower and higher Na+ levels were associated with a higher risk of mortality. While caring for CKD patients, greater attention to serum sodium levels by clinicians is warranted and could potentially help improve patient outcomes.

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.

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