scholarly journals Microvascular disease in chronic kidney disease: the base of the iceberg in cardiovascular comorbidity

2020 ◽  
Vol 134 (12) ◽  
pp. 1333-1356
Author(s):  
Uwe Querfeld ◽  
Robert H. Mak ◽  
Axel Radlach Pries
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscular Atrophy ◽  
Treatment Strategies ◽  
Microvascular Disease ◽  
Organ Damage ◽  
Cardiovascular Complications ◽  
Microvascular Density ◽  
Cardiovascular Comorbidity ◽  
Microvascular Rarefaction

Abstract Chronic kidney disease (CKD) is a relentlessly progressive disease with a very high mortality mainly due to cardiovascular complications. Endothelial dysfunction is well documented in CKD and permanent loss of endothelial homeostasis leads to progressive organ damage. Most of the vast endothelial surface area is part of the microcirculation, but most research in CKD-related cardiovascular disease (CVD) has been devoted to macrovascular complications. We have reviewed all publications evaluating structure and function of the microcirculation in humans with CKD and animals with experimental CKD. Microvascular rarefaction, defined as a loss of perfused microvessels resulting in a significant decrease in microvascular density, is a quintessential finding in these studies. The median microvascular density was reduced by 29% in skeletal muscle and 24% in the heart in animal models of CKD and by 32% in human biopsy, autopsy and imaging studies. CKD induces rarefaction due to the loss of coherent vessel systems distal to the level of smaller arterioles, generating a typical heterogeneous pattern with avascular patches, resulting in a dysfunctional endothelium with diminished perfusion, shunting and tissue hypoxia. Endothelial cell apoptosis, hypertension, multiple metabolic, endocrine and immune disturbances of the uremic milieu and specifically, a dysregulated angiogenesis, all contribute to the multifactorial pathogenesis. By setting the stage for the development of tissue fibrosis and end organ failure, microvascular rarefaction is a principal pathogenic factor in the development of severe organ dysfunction in CKD patients, especially CVD, cerebrovascular dysfunction, muscular atrophy, cachexia, and progression of kidney disease. Treatment strategies for microvascular disease are urgently needed.

Biochemical and Paraclinical Evaluation of Organ Damage in Arterial Hypertension with Associated Chronic Kidney Disease

2020 ◽  
Vol 71 (6) ◽  
pp. 194-204
Author(s):  
Teim Baaj ◽  
Ahmed Abu-Awwad ◽  
Mircea Botoca ◽  
Octavian Marius Cretu ◽  
Elena Ardeleanu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Ventricular Hypertrophy ◽  
Ankle Brachial Index ◽  
Intima Media Thickness ◽  
Organ Damage ◽  
Left Ventricular ◽  
Study Group ◽  
Group A

Organ damages, which contribute to the overall cardiovascular risk of hypertensive patients, should be early detected, prevented and treated. The study evaluated organ damage in a hypertensive study group with chronic kidney disease (CKD), compared with a study group of hypertension without CKD. Albuminuria was present in 41.2% and reduced estimated glomerular filtration rate [60 ml/min/m2 was present in 72.5% of hypertensive with CKD. The comparison of organ damage revealed in the CKD group a statistical significant higher prevalence of organ damage as follows: intima-media thickness ]0.9 mm in 39.9% vs 10.5%, carotid plaques in 28.2% vs 12.6%, left ventricular hypertrophy in 39.9% vs 31%, ankle brachial index in 6.2% vs 3.5%. Early detection and treatment of additional cardiovascular risk factors as dyslipidaemia and hyperglycaemia, that have significant role in the pathogenesis of organ damage, contribute to the better prevention of cardiovascular and renal complications in hypertension with CKD.

scholarly journals Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 936
Author(s):  
Chien-Lin Lu ◽  
Cai-Mei Zheng ◽  
Kuo-Cheng Lu ◽  
Min-Tser Liao ◽  
Kun-Lin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Wasting ◽  
Mesangial Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Tubulointerstitial Injury

The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines’ effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD’s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.

scholarly journals New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
José Pedraza-Chaverri ◽  
Laura G. Sánchez-Lozada ◽  
Horacio Osorio-Alonso ◽  
Edilia Tapia ◽  
Alexandra Scholze
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Cardiovascular Complications ◽  
Vitamin D Metabolism ◽  
Therapy Options ◽  
Mitochondrial Alterations ◽  
Inflammatory Processes ◽  
The Impact

In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline of kidney function and development of cardiovascular complications. We discuss the impact of mitochondrial alterations and dysfunction, a pathogenic role for hyperuricemia, and disturbances of vitamin D metabolism and signal transduction. Recent antioxidant therapy options including the use of vitamin D and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent), plant antioxidants, and food components as alternative antioxidant therapies.

scholarly journals THU0300 RISK FACTORS FOR COMPLICATIONS AND REFRACTORY COURSE IN PATIENTS WITH ANCA-ASSOCIATED SYSTEMIC VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 378.2-378
Author(s):  
A. Chudinov ◽  
I. Belyaeva ◽  
M. Pervakova ◽  
V. Mazurov ◽  
O. Inamova ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Induction Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Disease Risk ◽  
Systemic Vasculitis ◽  
Cardiovascular Complications ◽  
Infectious Complications ◽  
Eosinophilic Granulomatosis With Polyangiitis

Background:ANCA-associated systemic vasculitis (AAV) is characterized by a high incidence of complications and high mortality. The most significant complications during the first 3 years of the disease are infectious and cardiovascular. Development of chronic kidney disease also impairs the prognosis of AAV. Refractory to induction therapy can significantly increase the severity of organ lesions in patients with AAV.Objectives:The aim of this study was to determine risk factors for complications and refractory course in patients with AAV.Methods:Patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) were observed during the first 3 years of the disease and included in this study between 2010 and 2018. Most common infectious complications requiring inpatient treatment were pneumonia, mycosis, sepsis, purulent arthritis, purulent otitis media. Cardiovascular complications included pulmonary thromboembolism, myocardial infarction, ischemic stroke, venous thrombosis.Results:In total 209 (165 [79%] female and mean age 51.8 ± 13.2 years) AAV patients (94 GPA; 46 MPA; and 69 EGPA) were included in the analysis. Risk factors for infectious complications were BVAS level at the beginning of induction therapy > 25 (OR – 2.92, 95% CI (1.53;5.45) p<0.001), usage of prednisone in doses more than 60 mg / day at the induction of remission (OR – 2.76, 95% CI (1.45;5.29) p=0.003), usage of prednisone in doses ≥ 10 mg / day after 6 months of induction therapy (OR – 2.60, 95% CI (1.38;4.93) p=0.003), ANCA-PR3 positivity (OR – 2.25, 95% CI (1.13;4.46) p=0.017) and presence of diabetes mellitus in the AAV onset (OR – 1.77, 95% CI (1.14;3.45) p=0.038). Patients with AAV had following risk factors for cardiovascular complications: male (OR – 2.28, 95% CI (1.33;3.88) p=0.002), BVAS level > 25 (OR – 2.1, 95% CI (1.11;3.16) p=0.008) and presence of coronary artery disease in the AAV onset (OR – 2.2, 95% CI (1.18;4.10) p=0.015). ANCA positivity (OR – 5.62, 95% CI (2.1;14.9) p<0.001), presence of rapidly progressive glomerulonephritis in the first 3 months from onset AAV (OR – 5.02, 95% CI (3.42;7.35) p<0.001) and over 60 years of age (OR – 2.17, 95% CI (1.38;3.44) p=0.001) were risk factors of development of chronic kidney disease. Risk factors for refractory to induction therapy in patients with AAV were ANCA-PR3 positivity (OR – 3.13, 95% CI (1.63;6.02) p<0.001), BVAS level > 25 (OR – 2.63, 95% CI (1.74;4.34) p<0.001), initiation of therapy after 4 months from the onset of clinical manifestations (OR – 2.17, 95% CI (1.26;3.91) p=0.005). We additionally defined that identification of pathological phenotypes of alpha-1-antitrypsin was risk factors for refractory course in patients with GPA manifestations (OR – 2.66, 95% CI (1.12;6.33) p=0.048).Conclusion:Our study has shown that high disease activity, ANCA positivity and comorbid pathology increase risk of serious complications. Early administration of immunosuppressive therapy, adequate steroid dosing and use of risk factors for complications and refractory course in clinical practice can significantly improve the prognosis of AAV.Disclosure of Interests:None declared

Pediatric problems of stratification of the severity of stages, cardiovascular complications and renal forecast of chronic kidney disease by NKF-K / DOQI (2002) and KDIGO (2012) classifications

2021 ◽  
Vol 25 (3) ◽  
pp. 9-19
Author(s):  
N. D. Savenkova ◽  
O. P. Grigoreva
Keyword(s):  
Chronic Kidney Disease ◽  
High Risk ◽  
Kidney Disease ◽  
Pediatric Patients ◽  
Cardiovascular Complications ◽  
High Risk Group ◽  
Cardiovascular Pathology ◽  
Cardiovascular Prognosis ◽  
Renal Prognosis

Chronic kidney disease (CKD) in children is a global problem worldwide. The article discusses the problem of stratification of CKD severity according to the classifications of the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K / DOQI) (2002) and Kidney Disease Improving Global Outcomes (KDIGO) (2012) in pediatric patients. There are limitations in assessing severity of CKD stages C1-5 according to NKF-K / DOQI (2002) and KDIGO (2012) in children under 2 years of age who have a low glomerular filtration rate in contrast to adults. The stratification of the severity of stages 1-5 of CKD, cardiovascular complications and renal prognosis in children and adolescents according to the classifications NKF-K / DOQI (2002) [3] and KDIGO (2012) [14] are discussed. In adult patients with CKD, there is a compelling case for identifying of C3a and C3b sub stages in 3 stages of CKD according to KDIGO (2012) was that renal and cardiovascular prognosis are different with GFR 45-59 ml/min/1.73 m 2and GFR 30-44 ml/min/1.73 m 2 . The prognosis of the risk of developing cardiovascular diseases and complications for stages C2-5 in accordance with the KDIGO classification (2012) in children and adults differ. As follows from the publications, children with CKD in the pre-dialysis stages C2-4 form a high-risk group, with C4-5 on dialysis a group of very high risk of complications associated with cardiovascular pathology. Cardiovascular complications account for more than 30 % of all deaths of pediatric patients with CKD C4-5 on dialysis. The arguments justifying the allocation of CKD stages C1-5 in children under 2 years of age in accordance with the classification of NKF-K/DOQI (2002) are presented.

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