Stroke, CV disease and chronic kidney disease

Chronic kidney disease (CKD) is currently defined as the presence of proteinuria and/or an eGFR<60 mL/min/1.73m2 on the basis of the renal diagnosis. The global dimension of CKD is relevant, since its prevalence and incidence have doubled in the past three decades worldwide. A major complication that occurs in CKD patients is the development of cardiovascular (CV) disease, being the incidence rate of fatal/nonfatal CV events similar to the rate of ESKD in CKD. Moreover, CKD is a multifactorial disease where multiple mechanisms contribute to the individual prognosis. The correct development of novel biomarkers of CV risk may help clinicians to ameliorate the management of CKD patients. Biomarkers of CV risk in CKD patients are classifiable as prognostic, which help to improve CV risk prediction regardless of treatment, and predictive, which allow the selection of individuals who are likely to respond to a specific treatment. Several prognostic (cystatin C, cardiac troponins, markers of inflammation, and fibrosis) and predictive (genes, metalloproteinases, and complex classifiers) biomarkers have been developed. Despite previous biomarkers providing information on the pathophysiological mechanisms of CV risk in CKD beyond proteinuria and eGFR, only a minority have been adopted in clinical use. This mainly depends on heterogeneous results and lack of validation of biomarkers. The purpose of this review is to present an update on the already assessed biomarkers of CV risk in CKD and examine the strategies for a correct development of biomarkers in clinical practice. Development of both predictive and prognostic biomarkers is an important task for nephrologists. Predictive biomarkers are useful for designing novel clinical trials (enrichment design) and for better understanding of the variability in response to the current available treatments for CV risk. Prognostic biomarkers could help to improve risk stratification and anticipate diagnosis of CV disease, such as heart failure and coronary heart disease.

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Should We Consider the Cardiovascular System While Evaluating CKD-MBD?

Toxins ◽

10.3390/toxins12030140 ◽

2020 ◽

Vol 12 (3) ◽

pp. 140 ◽

Cited By ~ 2

Author(s):

Merita Rroji ◽

Andreja Figurek ◽

Goce Spasovski

Keyword(s):

Chronic Kidney Disease ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Mineral And Bone Disorder ◽

Disease Modifying Drugs ◽

Potential Association ◽

Bone Disorder ◽

Risk Of Progression ◽

Disease Modifying ◽

Cv Disease

Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early stages far exceeds the risk of progression to dialysis. The presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality. As a non-atheromatous process, it could be partially explained why standard CV disease-modifying drugs do not provide such an impact on CV mortality in CKD as observed in the general population. We summarize the potential association of CV comorbidities with the older (parathyroid hormone, phosphate) and newer (FGF23, Klotho, sclerostin) CKD-MBD biomarkers.

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Lipid disorders of patients with chronic kidney disease

10.1093/med/9780199592548.003.0102 ◽

2015 ◽

Author(s):

Alan G. Jardine ◽

Rajan K. Patel

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

Coronary Disease ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Strong Argument ◽

Lowering Therapy ◽

Coronary Events ◽

Cv Disease

The risk of developing cardiovascular (CV) disease is increased in patients with chronic kidney disease (CKD) and although dyslipidaemia is a major contributory factor to the development of premature CV disease, the relationship is complex. Changes in lipid fractions are related to glomerular filtration rate and the presence and severity of proteinuria, diabetes, and other confounding factors. The spectrum of CV disease changes from lipid-dependent, atheromatous coronary disease in early CKD to lipid-independent, non-coronary disease, manifesting as heart failure, and sudden cardiac death in advanced and end-stage renal disease. Statin-based lipid-lowering therapy is proven to reduce coronary events across the spectrum of CKD. The relative reduction in overall CV events, however, diminishes as CKD progresses and the proportion of lipid-dependent coronary events declines. There is nevertheless a strong argument for the use of statin-based therapy across the spectrum of CKD. The argument is particularly strong for those patients with progressive renal disease who will eventually require transplantation, in whom preventive therapy should start as early as possible. The SHARP study established the benefits and endorses the use of lipid-lowering therapy in CKD 3-4 but uncertainty about the value of initiation of statin therapy in CKD 5 remains. There is, however, no rationale for stopping agents started earlier in the course of the illness for compelling indications, particularly in those who will ultimately be transplanted. The place of high-density lipoprotein-cholesterol raising and triglyceride lowering therapy needs to be assessed in trials. Modifying dyslipidaemia in CKD has demonstrated that lipid-dependent atheromatous cardiovascular disease is only one component of the burden of CV disease in CKD patients, that this is proportionately less in advanced CKD, and that modification of lipid profiles is only one part of CV risk management.

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Chronic kidney disease and vascular remodelling: molecular mechanisms and clinical implications

Clinical Science ◽

10.1042/cs20120074 ◽

2012 ◽

Vol 123 (7) ◽

pp. 399-416 ◽

Cited By ~ 64

Author(s):

Marie Briet ◽

Kevin D. Burns

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Molecular Mechanisms ◽

Complex Disease ◽

Mineral Metabolism ◽

Renin Angiotensin System ◽

Cardiovascular Complications ◽

Arterial Calcification ◽

Clinical Consequences ◽

Cv Disease

CKD (chronic kidney disease) is a severe and complex disease with a very high prevalence of CV (cardiovascular) complications. CKD patients are exposed to haemodynamic disturbances in addition to severe metabolic abnormalities that lead to a specific form of arterial remodelling, which contributes to the development of CV disease. Arterial calcification is a major event in the arterial remodelling process and is strongly linked to mineral metabolism abnormalities associated with CKD. Arterial remodelling is not limited to arterial calcification and modifications in arterial wall composition are also observed. Activation of the RAS (renin–angiotensin system), ET-1 (endothelin-1), endothelial dysfunction, oxidative stress and ADMA (asymmetric ω-NG,NG-dimethylarginine), as well as the anti-aging molecule Klotho, are implicated in this process. The present review details the mechanisms involved in arterial calcification and arterial remodelling associated with CKD, and provides the clinical consequences of large and small artery stiffness and remodelling in CKD patients.

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Insulin resistance in chronic kidney disease: a systematic review

AJP Renal Physiology ◽

10.1152/ajprenal.00340.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. F1087-F1108 ◽

Cited By ~ 84

Author(s):

Belinda Spoto ◽

Anna Pisano ◽

Carmine Zoccali

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Molecular Mechanisms ◽

Vascular Dysfunction ◽

Left Ventricular ◽

Renal Diseases ◽

Cv Disease ◽

End Stage

Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the normal range and becoming almost universal in those who reach the end stage of kidney failure. The skeletal muscle represents the primary site of IR in CKD, and alterations at sites beyond the insulin receptor are recognized as the main defect underlying IR in this condition. Estimates of IR based on fasting insulin concentration are easier and faster but may not be adequate in patients with CKD because renal insufficiency reduces insulin catabolism. The hyperinsulinemic euglycemic clamp is the gold standard for the assessment of insulin sensitivity because this technique allows a direct measure of skeletal muscle sensitivity to insulin. The etiology of IR in CKD is multifactorial in nature and may be secondary to disturbances that are prominent in renal diseases, including physical inactivity, chronic inflammation, oxidative stress, vitamin D deficiency, metabolic acidosis, anemia, adipokine derangement, and altered gut microbiome. IR contributes to the progression of renal disease by worsening renal hemodynamics by various mechanisms, including activation of the sympathetic nervous system, sodium retention, and downregulation of the natriuretic peptide system. IR has been solidly associated with intermediate mechanisms leading to cardiovascular (CV) disease in CKD including left ventricular hypertrophy, vascular dysfunction, and atherosclerosis. However, it remains unclear whether IR is an independent predictor of mortality and CV complications in CKD. Because IR is a modifiable risk factor and its reduction may lower CV morbidity and mortality, unveiling the molecular mechanisms responsible for the pathogenesis of CKD-related insulin resistance is of importance for the identification of novel therapeutic targets aimed at reducing the high CV risk of this condition.

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Cardiovascular Morbidity and Mortality in Children with Chronic Kidney Disease in North America: Lessons from the Usrds and Naprtcs Databases

Peritoneal Dialysis International ◽

10.1177/089686080502503s31 ◽

2005 ◽

Vol 25 (3_suppl) ◽

pp. 120-122 ◽

Cited By ~ 25

Author(s):

Mark M. Mitsnefes

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

North America ◽

Cardiac Disease ◽

Cardiac Risk ◽

Morbidity And Mortality ◽

Cardiovascular Morbidity And Mortality ◽

Cv Disease ◽

Stage Renal Disease

Cardiovascular (CV) disease mortality has not changed in the past three decades, remaining the second most common cause of death in children with end-stage renal disease (ESRD). This article reviews pediatric data pertaining to CV disease obtained from the two largest renal databases in North America. The data indicate high incidence and prevalence of CV complications and cardiac risk factors in children with ESRD, accounting for high cardiac mortality in this patient population. Early identification and intervention to treat modifiable risk factors and asymptomatic cardiac disease might lead to prevention of cardiac disease and to a decrease in CV morbidity and mortality in young adults who developed chronic kidney disease during childhood.

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The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz242 ◽

2019 ◽

Cited By ~ 4

Author(s):

Francis Verbeke ◽

Justyna Siwy ◽

Wim Van Biesen ◽

Harald Mischak ◽

Anneleen Pletinck ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Cox Regression ◽

Total Mortality ◽

Independent Information ◽

Increased Risk ◽

Ckd Stage ◽

History Of ◽

Cv Disease ◽

Stratified Analysis

Abstract Background The urinary proteomic classifier chronic kidney disease 273 (CKD273) is predictive for the development and progression of chronic kidney disease (CKD) and/or albuminuria in type 2 diabetes. This study evaluates its role in the prediction of cardiovascular (CV) events in patients with CKD Stages G1–G5. Methods We applied the CKD273 classifier in a cohort of 451 patients with CKD Stages G1–G5 followed prospectively for a median of 5.5 years. Primary endpoints were all-cause mortality, CV mortality and the composite of non-fatal and fatal CV events (CVEs). Results In multivariate Cox regression models adjusting for age, sex, prevalent diabetes and CV history, the CKD273 classifier at baseline was significantly associated with total mortality and time to fatal or non-fatal CVE, but not CV mortality. Because of a significant interaction between CKD273 and CV history (P = 0.018) and CKD stages (P = 0.002), a stratified analysis was performed. In the fully adjusted models, CKD273 classifier was a strong and independent predictor of fatal or non-fatal CVE only in the subgroup of patients with CKD Stages G1–G3b and without a history of CV disease. In those patients, the highest tertile of CKD273 was associated with a >10-fold increased risk as compared with the lowest tertile. Conclusions The urinary CKD273 classifier provides additional independent information regarding the CV risk in patients with early CKD stage and a blank CV history. Determination of CKD273 scores on a random urine sample may improve the efficacy of intensified surveillance and preventive strategies by selecting patients who potentially will benefit most from early risk management.

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Prognostic potential of brain natriuretic peptide (BNP) in predialysis chronic kidney disease patients

Clinical Science ◽

10.1042/cs20040351 ◽

2005 ◽

Vol 109 (1) ◽

pp. 75-82 ◽

Cited By ~ 30

Author(s):

Susan J. CARR ◽

Sunita BAVANANDAN ◽

Barbara FENTUM ◽

Leong NG

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Natriuretic Peptide ◽

Cox Model ◽

High Sensitivity ◽

Hazard Ratio ◽

End Point ◽

Cv Disease ◽

Stage Renal Disease ◽

Overall Mortality

In the present study, we investigated the potential of N-BNP (N-terminal B-type natriuretic peptide) as a prognostic marker for risk of CV (cardiovascular) events, overall mortality and progression to ESRD (end-stage renal disease) in a cohort of 83 pre-dialysis CKD (chronic kidney disease) patients without clinical evidence of heart failure. During the study, ten patients reached the combined end point of overall mortality and/or CV event. Univariate factors associated with the combined end point were plasma N-BNP (P<0.0005), creatinine (P<0.002), systolic blood pressure (P<0.009) and age (P<0.015). N-BNP levels were higher in patients with CV events (P<0.0005). Cox model regression analysis yielded log10 N-BNP (hazard ratio, 9.608; P<0.007) and pre-existing CV disease (hazard ratio, 4.571; P<0.029) as independent predictors of overall mortality or CV events. Kaplan–Meier analysis curves for the subgroup with supramedian creatinine levels (225 μmol/l) showed significant separation of the curves stratified for plasma N-BNP levels above and below the group median (291 pmol/l) for all end points. Receiver-operator-characteristic curves for N-BNP (355 pmol/l cut-off) demonstrated a specificity of 65.8% at a sensitivity of 100% for predicting CV events/overall mortality. The measurement of plasma N-BNP may aid in the risk stratification of pre-dialysis CKD patients. The high sensitivity and negative predictive value (100%) may enable the selection of patients who could safely be excluded from further investigations, resulting in better focusing of resources.

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The challenge of early glomerular filtration rate decline in response to antihypertensive treatment and chronic kidney disease outcomes

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa171 ◽

2020 ◽

Author(s):

Lorenzo Signorini ◽

Gianluigi Zaza ◽

Giovanni Gambaro

Keyword(s):

Chronic Kidney Disease ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Filtration Rate ◽

Enzyme Inhibitor ◽

Response To Treatment ◽

Beneficial Effects ◽

Cv Disease ◽

The Impact

Abstract Hypertension and chronic kidney disease (CKD) are closely linked pathological processes. Combating high blood pressure (BP) is an essential part of preventing CKD progression and reducing cardiovascular (CV) risk. Data from recent randomized controlled trials on patients at high CV risk showed the beneficial effects of intensive action to meet BP targets on mortality related to CV disease. The impact of meeting such targets on renal function is still unclear, however, particularly for patients with CKD. This issue has been the object of several post hoc analyses because lowering BP definitely has a nephroprotective role, but the early decline in glomerular filtration rate (GFR) associated with antihypertensive therapies and strict BP targets is still a concern in nephrology clinical practice. The present review discusses the results of studies on this topic, focusing specifically on the clinical significance of early GFR decline in response to treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or to different BP targets, in terms of renal and CV outcomes, and how this tips the balance towards continuing or discontinuing antihypertensive therapy.

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Use of SGLT-2 Inhibitors in Patients with Chronic Kidney Disease

10.12788/jfp.0225 ◽

2021 ◽

Vol 70 (6 Supplement) ◽

Author(s):

Mottl

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

The United States ◽

Sodium Glucose Cotransporter ◽

Diabetes Status ◽

Equivalent Efficacy ◽

History Of ◽

Cv Disease ◽

Diabetes Family History ◽

Diabetes Family

KEY TAKEAWAYS • Chronic kidney disease (CKD) is common, occurring in 1 of 7 adults in the United States. • 9 out of 10 adults with CKD are unaware of it. • People with CKD have the same risk for cardiovascular (CV) death as people with known atherosclerotic heart disease. • The risk for CV events and death increases with worsening albuminuria and estimated glomerular filtration rate (eGFR). • Patients with risk factors for CKD (hypertension, diabetes, family history of CKD, or advancing age) should be screened by measuring both eGFR and urinary albuminto-creatinine ratio. • Sodium-glucose cotransporter-2 inhibitors are first-line agents for treatment of patients with type 2 diabetes mellitus and CKD or a history of atherosclerotic CV disease. • Dapagliflozin has demonstrated equivalent efficacy for reducing kidney events in patients with CKD irrespective of diabetes status, and a similar, ongoing trial with empaglifloz

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