scholarly journals Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease

2018 ◽  
Vol 115 (21) ◽  
pp. E4910-E4919 ◽  
Author(s):  
Juanjuan Zhao ◽  
Katherine Lupino ◽  
Benjamin J. Wilkins ◽  
Chengxiang Qiu ◽  
Jian Liu ◽  
...  

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

2021 ◽  
Vol 11 (20) ◽  
pp. 9677
Author(s):  
Takuji Iyama ◽  
Takaaki Sugihara ◽  
Tomoaki Takata ◽  
Hajime Isomoto

The early detection of a kidney injury is essential to protect against the progression of kidney damage owing to the progressive nature of chronic kidney disease. A renal biopsy is the gold standard for the assessment of pathological alterations such as interstitial fibrosis and glomerulosclerosis. However, there are concerns regarding potential complications including bleeding and a reduction in renal function. Ultrasound elastography is an ideal modality for assessing the alterations in various organs and diagnosing malignant tumors. This technique has the potential to help detect early changes in renal function and pathological alterations. However, the careful application and interpretation of this technique in the kidney is required because of its complex hemodynamics and architecture. Shear wave elastography is the most widely investigated technique among ultrasound elastography. This review aims to summarize the previous investigations of the kidney using shear wave elastography, particularly for renal malignancy, kidney transplantation, and chronic kidney disease. Additionally, we have highlighted the influencing factors concerning the practical measurement of renal elasticity.


2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.


2020 ◽  
Vol 6 (1) ◽  
pp. 55-60
Author(s):  
Khabib Barnoev ◽  
◽  
Sherali Toshpulatov ◽  
Nozima Babajanova ◽  

The article presents the results of a study to evaluate the effectiveness of antiaggregant therapy on the functional status of the kidneys in 115 patients with stage II and III chronic kidney disease on the basis of a comparative study of dipyridamole and allthrombosepin. Studies have shown that long-term administration of allthrombosepin to patients has led to improved renal function.


2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0001
Author(s):  
Junho Ahn ◽  
Katherine Raspovic ◽  
Dane Wukich ◽  
George Liu

Category: Midfoot/Forefoot Introduction/Purpose: With increasing rates of patients being newly diagnosed with diabetes mellitus, foot complications are becoming more common, which often lead to amputation. Compared to major lower extremity amputations, transmetatarsal amputations (TMA) are associated with lower cost, better function, and more aesthetically satisfactory results for patients. Renal failure has been shown to be a significant predictor of morbidity and mortality in lower extremity amputations at various levels. However, previous reports examining the effect of renal function on reamputation rates after TMA have been mixed. As a result, the purpose of this study was to evaluate renal dysfunction as a risk factor for reamputation after initial TMA during the 30-day perioperative period in a large population database. Methods: Patients under 90 years of age who underwent a TMA between 2012 and 2015 were retrospectively identified in the prospectively collected American College of Surgeons-National Surgical Quality Improvement Program® (ACS-NSQIP®) database using the Current Procedure Terminology (CPT) code 28805. Failure of the initial TMA was defined as reamputation in the 30-day perioperative period through corresponding CPT codes. From these criteria, a total of 1,775 patients were identified. More than 150 unique patient factors were included in the study, but glycated hemoglobin (HbA1C) was not reported by the ACS-NSQIP® database. Diabetes status was categorized into four groups: “Insulin” dependent, “Non-Insulin” dependent, or “None.” Filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and patients were categorized into stages of chronic kidney disease (CKD). Results: Over the 30-day perioperative period, the rate of reamputation after TMA was 6.5%. No statistical differences in age, gender, race, body-mass index, or level of pre-operative functional status were found between groups. Reamputation rates after TMA was significantly correlated with higher white blood cell counts (p<.00001), greater serum creatinine (p=.021), higher blood urea nitrogen (p=.021), type of glycemic control (p=.002), stage of CKD (p=.003), dialysis (p=.001), and pre-operative blood transfusion (p=.042). Stage IV-V CKD was associated with 75% increased odds of reamputation (OR=1.75, 95% CI=1.12-2.73), and higher stage of CKD was associated with greater reamputation rates (p=.003) where stage II CKD had the lowest reamputation rate (3.6%) and stage V with the highest reamputation rate (10.9%). A similar trend was seen with 30-day mortality (p<.00001). Conclusion: In the current study, CKD was significantly correlated with reamputation rates after TMA as well as 30-day mortality. In contrast to a previous report, dialysis was also associated with TMA failure and need for reamputation. Our findings corroborate previous findings correlating dialysis-dependent renal failure and mortality. Whether patients in certain stages of CKD would achieve better outcomes with higher-level amputation rather than a TMA should be investigated in future studies.


Author(s):  
Qiao Qin ◽  
Fangfang Fan ◽  
Jia Jia ◽  
Yan Zhang ◽  
Bo Zheng

Abstract Purpose An increase in arterial stiffness is associated with rapid renal function decline (RFD) in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether the radial augmentation index (rAI), a surrogate marker of arterial stiffness, affects RFD in individuals without CKD. Methods A total of 3165 Chinese participants from an atherosclerosis cohort with estimated glomerular filtration rates (eGFR) of ≥ 60 mL/min/1.73 m2 were included in this study. The baseline rAI normalized to a heart rate of 75 beats/min (rAIp75) was obtained using an arterial applanation tonometry probe. The eGFRs at both baseline and follow-up were calculated using the equation derived from the Chronic Kidney Disease Epidemiology Collaboration. The association of the rAIp75 with RFD (defined as a drop in the eGFR category accompanied by a ≥ 25% drop in eGFR from baseline or a sustained decline in eGFR of > 5 mL/min/1.73 m2/year) was evaluated using the multivariate regression model. Results During the 2.35-year follow-up, the incidence of RFD was 7.30%. The rAIp75 had no statistically independent association with RFD after adjustment for possible confounders (adjusted odds ratio = 1.12, 95% confidence interval: 0.99–1.27, p = 0.074). When stratified according to sex, the rAIp75 was significantly associated with RFD in women, but not in men (adjusted odds ratio and 95% confidence interval: 1.23[1.06–1.43], p = 0.007 for women, 0.94[0.76–1.16], p = 0.542 for men; p for interaction = 0.038). Conclusion The rAI might help screen for those at high risk of early rapid RFD in women without CKD.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Huai Leng Pisaniello ◽  
Mark C. Fisher ◽  
Hamish Farquhar ◽  
Ana Beatriz Vargas-Santos ◽  
Catherine L. Hill ◽  
...  

AbstractGout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3–5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) < 60 ml/min/1.73 m2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed—colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification—colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of < 30 mL/min/1.73 m2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daijin Ren ◽  
Tianlun Huang ◽  
Xin Liu ◽  
Gaosi Xu

Abstract Background Chronic kidney disease (CKD) are associated with acute myocardial infarction (AMI). High-sensitive cardiac troponin (hs-cTn) has been evidenced to enhance the early diagnostic accuracy of AMI, but hs-cTn levels are often chronically elevated in CKD patients, which reduces their diagnostic utility. The aim of this study was to derive optimal cutoff-values of hs-cTn levels in patients with CKD and suspected AMI. Methods In this retrospective paper, a total of 3295 patients with chest pain (2758 in AMI group and 537 in Non-AMI group) were recruited, of whom 23.1% were had an estimated glomerular filtration rate (eGFR) of < 60 mL min−1 (1.73 m2)−1. Hs-cTnI values were measured at presentation. Results AMI was diagnosed in 83.7% of all patients. The optimal value of hs-TnI in diagnosing AMI was 1.15 ng mL−1, which were higher in males than females comparing different cutoff-values of subgroups divided by age, gender and renal function, and which increased monotonically with decreasing of eGFR because in patients with CKD without AMI, the correlation between hs-cTnI and renal function is low but significant (r2 = 0.067, P < 0.001). Conclusions Different optimal cutoff-values of hs-cTnI in the diagnosis of AMI in patients with CKD were helpful to the clinical diagnosis of AMI in various populations and were higher in males than females, but which was needed to be validated by multicenter randomized controlled clinical studies in the future.


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