Peptide block of constitutively activated Na+ channels in Liddle's disease

1996 ◽  
Vol 270 (1) ◽  
pp. C214-C223 ◽  
Author(s):  
I. I. Ismailov ◽  
B. K. Berdiev ◽  
C. M. Fuller ◽  
A. L. Bradford ◽  
R. P. Lifton ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Na Channel ◽  
Na Channels ◽  
Increased Risk ◽  
Carboxy Terminal Region ◽  
Stage Renal Disease ◽  
Carboxy Terminal ◽  
End Stage ◽  
Epithelial Na Channel ◽  
Constitutively Active

Hypertension is a multifactorial disorder that results in an increased risk of cardiovascular and end-stage renal disease. Liddle's disease represents a specific hypertensive disease and expresses itself in the human population as an autosomal dominant trait. Recent experimental evidence indicates that patients with Liddle's disease have constitutively active amiloride-sensitive Na+ channels and that these channels are phenotypically expressed in lymphocytes obtained from normal and affected members of the original Liddle's kindred. Linkage analysis indicates that this disease results from a deletion of the carboxy-terminal region of the beta-subunit of a recently cloned epithelial Na+ channel (ENaC). We report the successful immunopurification and reconstitution of both normal and constitutively active lymphocyte Na+ channels into planar lipid bilayers. These channels display all of the characteristics typical of renal Na+ channels, including sensitivity to protein kinase A phosphorylation. We demonstrate that gating of normal Na+ channels is removed by cytoplasmic trypsin digestion and that the constitutively active Liddle's Na+ channels are blocked by a beta- or gamma-ENaC carboxy-terminal peptide in a GTP-dependent fashion.

Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?

2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Close Association ◽  
Omega 3 ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.

scholarly journals Uremic Toxins and Their Relation with Oxidative Stress Induced in Patients with CKD

2021 ◽  
Vol 22 (12) ◽  
pp. 6196
Author(s):  
Anna Pieniazek ◽  
Joanna Bernasinska-Slomczewska ◽  
Lukasz Gwozdzinski
Keyword(s):  
Oxidative Stress ◽  
Uremic Toxins ◽  
Water Medium ◽  
Induce Insulin Resistance ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
End Stage

The presence of toxins is believed to be a major factor in the development of uremia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Uremic toxins have been divided into 3 groups: small substances dissolved in water, medium molecules: peptides and low molecular weight proteins, and protein-bound toxins. One of the earliest known toxins is urea, the concentration of which was considered negligible in CKD patients. However, subsequent studies have shown that it can lead to increased production of reactive oxygen species (ROS), and induce insulin resistance in vitro and in vivo, as well as cause carbamylation of proteins, peptides, and amino acids. Other uremic toxins and their participation in the damage caused by oxidative stress to biological material are also presented. Macromolecules and molecules modified as a result of carbamylation, oxidative stress, and their adducts with uremic toxins, may lead to cardiovascular diseases, and increased risk of mortality in patients with CKD.

scholarly journals Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Cristina Mega ◽  
Edite Teixeira-de-Lemos ◽  
Rosa Fernandes ◽  
Flávio Reis
Keyword(s):  
Type 2 Diabetes ◽  
Current Knowledge ◽  
Diabetic Patients ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Increased Risk ◽  
Long Time ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is now the single commonest cause of end-stage renal disease (ESRD) worldwide and one of the main causes of death in diabetic patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic control but also ameliorate dysfunction in various diabetes-targeted organs, especially the kidney, due to putative underlying cytoprotective properties, namely, its antiapoptotic, antioxidant, anti-inflammatory, and antifibrotic properties. Despite overall recommendations, many patients spend a long time well outside the recommended glycaemic range and, therefore, have an increased risk for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly, the prevention of pancreatic deterioration and the evolution of complications, such as DN. This review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin, namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney lesions, and cytoprotective properties.

Abstract 145: Rates of Transfusion and Progression to End-Stage Renal Disease in Chronic Kidney Disease Patients Undergoing Transradial Versus Transfemoral Cardiac Catheterization - An Analysis from the VA CART Program

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Amit N Vora ◽  
Maggie A Stanislawski ◽  
John S Rumsfeld ◽  
Thomas M Maddox ◽  
Mladen Vidovich ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Catheterization ◽  
High Risk Population ◽  
Post Procedure ◽  
Increased Risk ◽  
Significant Difference ◽  
Independent Association ◽  
Stage Renal Disease ◽  
End Stage

Background: Patients with chronic kidney disease (CKD) are at increased risk of bleeding and transfusion after cardiac catheterization. Whether rates of these complications or progression to new dialysis are increased in this high-risk population undergoing transradial (TR) access compared to transfemoral (TF) access is unknown. Methods: From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program between 10/2007-09/2012 we identified 40,160 CKD patients undergoing cardiac catheterization with baseline glomerular filtration rate (GFR) ≤ 60 ml/min. We used multivariable Cox modeling to determine the independent association between TR access and post-procedure transfusion as well as progression to new dialysis using TF as the reference. Results: Overall, 3,828 (9.5%) of CKD patients underwent TR access and tended to be slightly younger but overall had similar rates of CKD severity compared with TF patients (GFR 45-60 ml/min: 77.0% vs. 77.0%; GFR 30-44 ml/min: 19.7% vs. 19.3%; GFR 15-29 ml/min: 3.3% vs. 3.7%, p=0.35). TR patients had longer fluoroscopy times (8.1 vs 6.9 minutes, p=<0.0001) but decreased contrast use (90.0 vs 100.0 ml, p=<0.0001). Among the 31,692 patients with a full year of follow-up, 42 (1.7%) of TR patients and 545 (1.9%) of TF patients progressed to new dialysis within 1 year (p=0.64). However, only 33 (0.9%) of TR patients compared with 570 TF patients (1.6%) needed post-procedure blood transfusion (p=0.0006). After multivariable adjustment, there was no significant difference in progression to ESRD between TR and TF patients but TR was associated with a significant decrease in transfusion (Figure). Conclusion: Among CKD patients undergoing cardiac catheterization in the VA health system, TR access is associated with a decreased risk for post-procedure transfusion compared with TF access. There was no significant difference between the two approaches with respect to progression to ESRD. These data suggest that TR is a reasonable option for patients with any level of CKD undergoing cardiac catheterization.

scholarly journals Anticoagulation in Patients with End-Stage Renal Disease and Atrial Fibrillation: Confusion, Concerns and Consequences

2020 ◽  
Vol 22 (3) ◽  
pp. 306-316
Author(s):  
Narender Goel ◽  
Deepika Jain ◽  
Danny B. Haddad ◽  
Divya Shanbhogue
Keyword(s):  
Atrial Fibrillation ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Clinical Decision Making ◽  
Controlled Trial ◽  
Oral Anticoagulants ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

End-stage renal disease (ESRD) patients have a higher prevalence of diabetes mellitus, hypertension, congestive heart failure and advanced age, along with an increased incidence of non-valvular atrial fibrillation (AF), thereby increasing the risk for cerebrovascular accidents. Systemic anticoagulation is therefore recommended in patients with ESRD with AF to reduce the risk and complications from thromboembolism. Paradoxically, these patients are at an increased risk of bleeding due to great degree of platelet dysfunction and impaired interaction between platelet and endothelium. Currently, CHA2DS2-VASc and Hypertension, Abnormal liver/kidney function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol (HAS-BLED) are the recommended models for stroke risk stratification and bleeding risk assessment in patients with AF. There is conflicting data regarding benefits and risks of medications such as antiplatelet agents, warfarin and direct oral anticoagulants in ESRD patients with AF. Moreover, there is no randomized controlled trial data to guide the clinical decision making. Hence, a multi-disciplinary approach with annual re-evaluation of treatment goals and risk-benefit assessment has been recommended. In this article, we review the current recommendations with risks and benefits of anticoagulation in patients with ESRD with AF.

scholarly journals Increased Risk of End-Stage Renal Disease in Familial IgA Nephropathy

2002 ◽  
Vol 13 (2) ◽  
pp. 453-460
Author(s):  
Francesco Paolo Schena ◽  
Giuseppina Cerullo ◽  
Michele Rossini ◽  
Salvatore Giovanni Lanzilotta ◽  
Christian D’Altri ◽  
...  
Keyword(s):  
Renal Disease ◽  
Iga Nephropathy ◽  
End Stage Renal Disease ◽  
Upper Respiratory Tract ◽  
Renal Survival ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
Tract Infections ◽  
End Stage

ABSTRACT. Primary IgA nephropathy (IgAN) is characterized by recurrent episodes of macroscopic hematuria accompanied by upper respiratory tract infections or persistent asymptomatic microscopic hematuria with or without proteinuria. IgAN may involve one or more members of a family. Three generations of a cohort of 110 patients with biopsy-proven IgAN, living in Southern Italy, were checked for urinalysis, and the relative risk (RR) of developing the disease was evaluated. A total of 19 unrelated familial, 37 suspected, and 54 sporadic cases of IgAN were identified. Renal survival was estimated by the Kaplan-Meier method for censored data and compared by use of the log-rank test. More than 50% of the patients with IgAN clustered in kindred with more than two probably affected relatives. In 19 unrelated IgAN families, 8 had single-generation (SG) and 11 multigenerational (MG) involvement showing a prevalent vertical transmission of the trait. The RR was 16 times higher in first-degree relatives (odds ratio [OR], 16.4; 95% confidence interval [CI], 5.7 to 47.8; P < 0.0001) and >2 times higher, even if NS, in second-degree relatives (OR, 2.4; 95 % CI, 0.7 to 7.9; P = 0.145). The clinical and histologic picture of familial and sporadic IgAN appeared to be similar. The 20-yr renal survival rate from the apparent onset of the disease was significantly poorer in patients with familial (41%) than in patients with sporadic (94%) IgAN (P = 0.003). Furthermore, 15-yr renal survival from the time of renal biopsy was significantly worse in familial IgAN (P = 0.02); end-stage renal disease was present in 64% of familial and only in 8% of patients with sporadic IgAN. Finally, renal survival was significantly worse in patients belonging to families with SG rather than with MG involvement (P = 0.03). These data show, for the first time, that familial IgAN may be considered a nonbenign disease that occurs frequently in first-degree relatives. Familial IgAN has a poorer outcome than sporadic IgAN. Therefore, an accurate family history and urinalysis in all family members is urgently recommended in clinical practice. This procedure might avoid late referral of subjects with persistent and underestimated urinary abnormalities and late diagnosis of the disease.

scholarly journals Lithium and Renal Impairment: A Review on a Still Hot Topic

2018 ◽  
Vol 51 (05) ◽  
pp. 200-205 ◽  
Author(s):  
René Nielsen ◽  
Lars Kessing ◽  
Willem Nolen ◽  
Rasmus Licht
Keyword(s):  
Renal Impairment ◽  
Lithium Treatment ◽  
Serum Levels ◽  
Sound Studies ◽  
Renal Outcome ◽  
Unipolar Disorder ◽  
Increased Risk ◽  
The 1960S ◽  
Stage Renal Disease ◽  
End Stage

Abstract Introduction Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment, after long-term use, lithium might be underutilized. Methods This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. Results An increased risk of renal impairment associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound studies do not. Discussion The improved renal outcome found in the more recent lithium studies may be a result of improved monitoring and focus on recommended serum levels (preferentially 0.6–0.8 mmol/L) as compared to poorer renal outcome in studies with patients treated in the 1960s to 1980s.

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