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.

scholarly journals Urine Osmolarity and Risk of Dialysis Initiation in a CKD Cohort

2015 ◽  
Vol 66 (Suppl. 3) ◽  
pp. 14-17 ◽  
Author(s):  
Lise Bankir ◽  
Max Plischke ◽  
Nadine Bouby ◽  
Martin Haas
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Association Studies ◽  
Experimental Studies ◽  
Dialysis Initiation ◽  
Hazards Model ◽  
Baseline Creatinine ◽  
Stage Renal Disease ◽  
End Stage ◽  
Disease Stages

Background: Several experimental studies in rats and a few association studies in humans suggest that the antidiuretic action of vasopressin may accelerate the progression of chronic kidney disease. We undertook a retrospective analysis in a monocentric cohort of 273 patients with chronic kidney disease stages 1-4, focusing on a strong variable of interest, urinary osmolarity, and a strong endpoint, dialysis initiation. Data was analyzed in a multivariate proportional sub-distribution hazards model for competing risk data with appropriate co-variates. Main Results: Over a median follow-up period of 92 months, dialysis was initiated in 105 patients. After adjustments for baseline creatinine clearance, and other confounding factors, a higher risk for initiation of dialysis was found in patients with higher urinary osmolarity. After 72 months, the estimated adjusted cumulative incidence probability for dialysis initiation was 15, 24, and 34% in patients with baseline urinary osmolarity of 315, 510, and 775 mosm/l, respectively (p = 0.033). Key Messages: In this retrospective, longitudinal study, a higher baseline urinary osmolarity was strongly associated with a higher risk of end-stage renal disease (after appropriate adjustments). Further, prospective studies are required to evaluate the possible benefit of interventions aiming at reducing urinary osmolarity as a potential treatment for slowing chronic kidney disease progression.

Buffering chronic kidney disease with sodium bicarbonate

2018 ◽  
Vol 132 (17) ◽  
pp. 1999-2001 ◽  
Author(s):  
Emily N. Williams ◽  
Keisa W. Mathis
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
End Stage Renal Disease ◽  
Filtration Rate ◽  
Experimental Studies ◽  
Progressive Loss ◽  
Research Findings ◽  
Stage Renal Disease ◽  
End Stage

The roles of the kidney are well defined, if there is a progressive loss in renal function, the kidney is no longer able to perform the listed tasks and chronic kidney disease (CKD) persists. In both clinical and experimental studies, NaHCO3 supplementation has been shown to improve glomerular filtration rate (GFR) as well as halt the progression toward end-stage renal disease (ESRD). In an article recently published in Clinical Science (vol 132 (11) 1179-1197), Ray et al. presented an intriguing and timely study, which investigates the mechanisms involved in the protection that follows oral NaHCO3 ingestion. Here we comment on their research findings.

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 Modified arteriosclerosis score predicts the outcomes of diabetic kidney disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yifan Zhang ◽  
Qifeng Jiang ◽  
Jianteng Xie ◽  
Chunfang Qi ◽  
Sheng Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Interstitial Fibrosis ◽  
Smooth Muscle Actin ◽  
Prognostic Indicators ◽  
Urine Protein ◽  
Tubular Atrophy ◽  
Diabetic Kidney ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background The significance of renal arteriosclerosis in the prediction of the renal outcomes of diabetic kidney disease (DKD) remains undetermined. Methods We enrolled 174 patients with DKD from three centres from January 2010 to July 2017. The severity and extent of arteriosclerosis were analysed on sections based on dual immunohistochemical staining of CD31 and α-smooth muscle actin. An X-tile plot was used to determine the optimal cut-off value. The primary endpoint was renal survival (RS), defined as the duration from renal biopsy to end-stage renal disease or death. Results The baseline estimated glomerular filtration rate (eGFR) of 135 qualified patients was 45 (29 ~ 70) ml/min per 1.73 m2, and the average 24-h urine protein was 4.52 (2.45 ~ 7.66) g/24 h. The number of glomeruli in the biopsy specimens was 21.07 ± 9.7. The proportion of severe arteriosclerosis in the kidney positively correlated with the Renal Pathology Society glomerular classification (r = 0.28, P < 0.012), interstitial fibrosis and tubular atrophy (IFTA) (r = 0.39, P < 0.001), urine protein (r = 0.213, P = 0.013), systolic BP (r = 0.305, P = 0.000), and age (r = 0.220, P = 0.010) and significantly negatively correlated with baseline eGFR (r = − 0.285, P = 0.001). In the multivariable model, the primary outcomes were significantly correlated with glomerular class (HR: 1.72, CI: 1.15 ~ 2.57), IFTA (HR: 1.96, CI: 1.26 ~ 3.06) and the modified arteriosclerosis score (HR: 2.21, CI: 1.18 ~ 4.13). After risk adjustment, RS was independently associated with the baseline eGFR (HR: 0.97, CI: 0.96 ~ 0.98), urine proteinuria (HR: 1.10, CI: 1.04 ~ 1.17) and the modified arteriosclerosis score (HR: 2.01, CI: 1.10 ~ 3.67), and the nomogram exhibited good calibration and acceptable discrimination (C-index = 0.82, CI: 0.75 ~ 0.87). Conclusions The severity and proportion of arteriosclerosis may be helpful prognostic indicators for DKD.

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

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.

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