Cardiovascular risk in chronic kidney disease

National Kidney Foundation guidelines define chronic kidney disease (CKD) as persistent kidney damage (confirmed by renal biopsy or markers of kidney damage) and/or glomerular filtration rate (GFR) <60 mL/min/1.73m2 for greater than three months. Patients with CKD experience higher mortality and adverse cardiovascular (CV) event rates, which remains significant after adjustment for conventional coronary risk factors. This progressive CV risk associated with worsening renal function may be explained by other factors that become increasingly important with renal decline. In this regard, more investigation of nonconventional factors that have received a lot of attention includes associations with inflammation, albuminuria, reduced vascular compliance, and homocysteine. In addition, individuals with CKD encounter the problem of "therapeutic nihilism," in which there is a lack of appropriate risk factor modification and intervention, despite established awareness of their high cardiovascular risk. Several studies suggest that these individuals derive as much, if not more, benefit from evidence-based cardiovascular therapies and strategies. Greater educational efforts are needed to reduce this therapeutic gap.     

Cardiovascular risk in chronic kidney disease (CKD): the CKD-mineral bone disorder (CKD-MBD)

Recent advances in our understanding of the excess mortality of chronic kidney disease (CKD) due to cardiovascular complications, obtained through observational studies, demonstrate that vascular calcification and hyperphosphatemia are major cardiovascular risk factors. Mechanistic studies demonstrate that these two risk factors are related and that hyperphosphatemia directly stimulates vascular calcification. The role of hyperphosphatemia in stimulating vascular calcification in CKD is associated with a block to the skeletal reservoir function in phosphate balance due to excess bone resorption. This has led to the realization that renal osteodystrophy is linked to vascular calcification by disordered mineral homeostasis (phosphate) and that a multiorgan system fails in CKD, leading to cardiovascular mortality. In children with renal disease, the multiorgan system fails, just as in adults, but the outcomes have been less well studied, and perceptions of differences from adults are possibly incorrect. Vascular calcification and cardiovascular mortality are less prevalent among pediatric patients, but they are present. However, CKD-induced vascular disease causes stiffness of the arterial tree causing, in turn, systolic hypertension and left ventricular hypertrophy as early manifestations of the same pathology in the adult. Because of the role of the skeleton in these outcomes, renal osteodystrophy has been renamed as the CKD mineral bone disorder (CKD-MBD). This review, which focuses on the pediatric patient population, describes our current state of knowledge with regards to the pathophysiology of the CKD-MBD, including the new discoveries related to early stages of CKD. As a new necessity, cardiovascular function issues are incorporated into the CKD-MBD, and new advances in our knowledge of this critical component of the disorder will lead to improved outcomes in CKD.     

Cardiovascular risk assessment in children with chronic kidney disease

Chronic kidney disease (CKD) is a major factor contributing to cardiovascular (CV) morbidity and mortality with the highest risk in patients on dialysis. An estimation of CV risk is important not only to identify potential modifiable risk factors but also to evaluate the effect of treatments aimed to reduce the risk. Non-invasive methods of measuring vascular changes and circulating biomarkers are available to assess the presence and severity of cardiovascular damage. These include measures of structural (carotid intima-media thickness and coronary artery calcification score) and functional (aortic pulse wave velocity, 24-h ambulatory blood pressure monitoring, ambulatory arterial stiffness index, heart rate variability and flow-mediated dilatation) changes in the vessel wall. In addition, a number of circulating biomarkers of vascular damage and its progression have been studied. Many of these tests are well validated as surrogate markers of future cardiovascular events and death in adult CKD patients, but need technical adaptation, standardization and validation for use in children. With our current state of knowledge, these are best reserved for research studies and scarce clinical resources may be better utilized for preventative strategies to reduce the modifiable risk factors for calcification from early CKD stages.     

Cardiovascular disease in children with chronic kidney disease

More than a decade ago, cardiovascular disease (CVD) was recognized as a major cause of death in children with advanced CKD. This observation has sparked the publication of multiple studies assessing cardiovascular risk, mechanisms of disease, and early markers of CVD in this population. Similar to adults, children with CKD have an extremely high prevalence of traditional and uremia-related CVD risk factors. Early markers of cardiomyopathy, such as left ventricular hypertrophy and dysfunction, and early markers of atherosclerosis, such as increased carotid artery intima-media thickness, carotid arterial wall stiffness, and coronary artery calcification, are frequently present in these children, especially those on maintenance dialysis. As a population without preexisting symptomatic cardiac disease, children with CKD potentially receive significant benefit from aggressive attempts to prevent and treat CVD. Early CKD, before needing dialysis, is the optimal time to both identify modifiable risk factors and intervene in an effort to avert future CVD. Slowing the progression of CKD, avoiding long-term dialysis and, if possible, conducting preemptive transplantation may represent the best strategies to decrease the risk of premature cardiac disease and death in children with CKD.     

Cardiovascular disease in patients with chronic kidney disease

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with renal failure. Patients with chronic kidney disease have significant CVD, and carry a high cardiovascular burden by the time they commence renal replacement therapy (RRT). The severity of CVD that has been observed in dialysis patients lead to a growing body of research examining the pathogenesis and progression of CVD during the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) (ie, predialysis phase). Multiple factors are involved in the development of CVD in CKD. More importantly, critical and key factors seem to develop early in the course of CKD, and result in preventable worsening of CVD in this patient population. Anemia is common in patients with CKD, and has been shown to have an independent role in the genesis of left ventricular hypertrophy (LVH) and subsequent CVD. Unfortunately, it is underdiagnosed and undertreated in patients with CKD. Early intervention, and better correction of anemia, seems to gain a great momentum in the prevention and management of CVD in CKD. Hypertension is another risk factor that has been targeted by the National Kidney Foundation Task Force on CVD in chronic kidney disease. This article reviews the different factors involved in the pathogenesis of CVD in CKD and the evidence supporting early and aggressive intervention.     

Cardiovascular disease in children with chronic kidney disease

In children with end-stage renal disease (ESRD), cardiovascular disease (CVD) mortality has not changed for the past 3 decades. Cardiac disease remains the second most common cause of death. Recent data demonstrate a high incidence and prevalence of traditional and chronic kidney disease (CKD)-related CVD risk factors in children. Early markers of cardiomyopathy, such as left ventricular hypertrophy (LVH) and left ventricular dysfunction (LV dysfunction), and early markers of atherosclerosis, such as increased carotid artery intima-media thickness (IMT) and carotid arterial wall stiffness, are frequently found in this patient population. Early identification of modifiable risk factors and treatment of asymptomatic CVD might lead to decrease of cardiovascular morbidity and mortality in young adults who developed CKD during childhood.     

Cardiovascular complications of pediatric chronic kidney disease

Cardiovascular disease (CVD) mortality is a leading cause of death in adult chronic kidney disease (CKD), with exceptionally high rates in young adults, according to the Task Force on Cardiovascular Disease. Recent data indicate that cardiovascular complications are already present in children with CKD. This review summarizes the current literature on cardiac risk factors, mortality and morbidity in children with CKD.     

Anaemia management in patients with chronic kidney disease: Taiwan practice guidelines

The introduction of erythropoiesis‐stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non‐dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin‐α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10–11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation.     

Cardiovascular disease in chronic kidney disease from a cardiologist's perspective

PURPOSE OF REVIEW: Cardiovascular disease accounts for the majority of morbidity and mortality in patients with chronic kidney disease (CKD). This review therefore concentrates on CKD from the viewpoint of the cardiologist. RECENT FINDINGS: Studies have identified several explanations for this observation, including high rates of risk factors for cardiovascular disease, lesser use of cardioprotective strategies, adverse outcomes with cardiovascular drugs and procedures, and accelerated atherosclerosis and myocardial disease in CKD. Because recent studies have rigorously controlled for confounding factors, there is an emerging recognition that CKD is an independent cardiovascular risk state. Conversely, CKD appears to be the result of systemic atherosclerosis. The relative under-utilization of cardioprotective therapies has been an increasingly reported finding in the literature. It appears that conventional cardiovascular risk factor reduction in both the chronic and acute care settings has a greater relative benefit in those patients with CKD than in those with normal renal function. SUMMARY: CKD is an independent cardiovascular risk state. Hence, there is a strong rationale for research in CKD patients into the pathogenesis of CVD. In addition, there are multiple opportunities for improving cardiovascular outcomes in patients with CKD, including both chronic and acute cardiovascular risk reduction.     

Disease management in chronic kidney disease

Chronic kidney disease (CKD) is a growing health problem of epidemic proportions both in the United States and worldwide. The care of CKD patients, before and after starting dialysis, remains highly fragmented resulting in suboptimal clinical outcomes and high costs, creating a high burden of disease on patients and the health care system. Disease management (DM) is an approach to coordinating care for this complex population of patients that has the promise of improving outcomes and constraining costs. For CKD patients not yet on dialysis, the major goals of a DM program are (1) early identification of CKD patients and therapy to slow the progression of CKD, (2) identification and management of the complications of CKD per se, (3) identification and management of the complications of comorbid conditions, and (4) smooth transition to renal replacement therapy. For those CKD patients on dialysis, focused attention on avoidable hospitalizations is a key to a successful DM program. Multidisciplinary collaboration among physicians (nephrologist, primary care physician, cardiologist, endocrinologist, vascular surgeons, and transplant physicians) and participating caregivers (nurse, pharmacist, social worker, and dietician) is critical as well. There are several potential barriers to the successful implementation of a CKD/end-stage renal disease DM program, including lack of awareness of the disease state among patients and health care providers, late identification and referrals to a nephrologist, complex fragmented care delivered by multiple providers in many different sites of care, and reimbursement that does not align incentives for all involved. Recent experience suggests that these barriers can be overcome, with DM becoming a promising approach for improving outcomes for this vulnerable population.     

Predictive cardiovascular risk factors in patients with chronic kidney disease (CKD)

BACKGROUND: Traditional cardiovascular risk factors and uremia-related specific factors have been identified in patients with CKD, explaining the highest risk for morbidity and mortality from cardiovascular disease. The aim of this study was to analyze the predictive power of several cardiovascular risk factors and markers in a population of stable patients with moderate CKD. METHODS: One hundred twenty-eight (78 M, 50 F) outpatients with estimated glomerular filtration rate (GFR) <60 mL/min were included in the study. Medical records about cardiovascular factors were recorded. Analytical parameters and cardiac markers were analyzed. The patients were prospectively followed, and the end points were fatal and nonfatal cardiovascular events. RESULTS: After a mean follow-up of 22.3 months, 27 patients had a cardiovascular event. The patients who suffered a cardiovascular event were older (P= 0.002), with more anemia (P= 0.014), higher pulse pressure (P= 0.011), and cTnT levels (P= 0.000). In addition, they had more prevalence of LVH (P= 0.001), diabetes (P= 0.013), previous coronary heart disease (P= 0.008), chronic heart failure (P= 0.000), vascular peripheral disease (P= 0.006), and had also a higher score of 10-year coronary heart disease predicted risk (P= 0.006). Age [hazard ratio (HR) 1.07, P= 0.02], previous coronary artery disease (HR 4.08, P= 0.0012), and cTnT levels (HR 1.64, P= 0.0000) independently predicted cardiovascular events on multivariate Cox analysis. CONCLUSION: In stable patients with CKD, age and previous coronary artery disease were the traditional cardiovascular risk factors more predictive for cardiovascular events. Cardiac troponin T is a powerful marker of cardiovascular events in CKD patients.     

Cardiovascular calcification in nondialyzed patients with chronic kidney disease

Chronic kidney disease (CKD) has become a major health-care problem of global proportions. Progression to end-stage renal disease (ESRD), the need for renal replacement therapy, and the high annual death rate of dialysis patients are the most noticeable outcomes of CKD. Less appreciated, however, is the fact that most patients with CKD actually die mainly from cardiovascular disease, rather than progress to ESRD. Coronary artery calcification (CAC), a surrogate marker of atherosclerosis, is common in dialysis and CKD patients. Coronary artery calcium scores, as measured by ultrafast computed tomography, is an independent predictor of future cardiac events. Using this technique, several studies have documented extensive calcification in dialysis patients, a subject of several exhaustive reviews. Unfortunately, much less attention has been paid to calcification in nondialyzed patients with CKD. In this review, I will emphasize the fact that CVC is common in patients with CKD not yet on dialysis, develops early in the course of CKD, and worsens with the decline in renal function particularly among diabetics who progressed to ESRD. I will also discuss the pathogenesis of CVC in CKD patients and highlight the lack of a major role for abnormalities of mineral metabolism in the pathogenesis of calcification in CKD patients. In addition to the high prevalence of traditional risk factors for CAD, the presence of proteinuria, reduced renal function, diabetic nephropathy, and the rate of progression to ESRD may represent the main uremia-related factors that increase the risk for calcification in CKD. Finally, I will review the protective role of inhibitors of calcification in CKD.     

Cardiovascular disease risk factors in chronic renal insufficiency

BACKGROUND: Coronary heart disease (CHD) is an important cause of morbidity and mortality in end-stage renal disease (ESRD). Prevention of CHD in ESRD requires identification and treatment of coronary risk factors in chronic renal insufficiency (CRI). METHODS: We evaluated the prevalence of "traditional coronary risk factors" in CRI in 1,795 patients enrolled in the baseline period of Modification of Diet in Renal Disease (MDRD) Study. Using a cross-sectional design, we determined the relationship of these risk factors to the level of glomerular filtration rate (GFR) and proteinuria. We also predicted the CHD risk in the MDRD Study baseline cohort using the coronary point score. RESULTS: 64.0% had blood pressure > or = 130/85 mmHg despite antihypertensive therapy. 64.2% had LDL cholesterol > or = 130 mg/dl, while 38.3% had HDL cholesterol < 35 mg/dl. After adjustment for age, gender and the presence of diabetes, GFR was inversely associated with systolic blood pressure and positively associated with HDL cholesterol, but not associated with total or LDL cholesterol. After adjustment for age. gender and the presence of diabetes, proteinuria was positively associated with systolic and diastolic blood pressure, total serum cholesterol and LDL cholesterol, and inversely associated with HDL cholesterol. Nonetheless, the predicted CHD risk, even at a very low GFR, was similar to the risk in the general population and lower than the observed rate of de novo CHD in incident dialysis patients. CONCLUSIONS: "Traditional coronary risk factors" are highly prevalent in CRI and vary with the level of renal function. However, the coronary point score does not appear to explain the extent of increased CHD risk in ESRD. Non-traditional risk factors may also contribute to CHD in ESRD.     

Building the chronic kidney disease management team

The need to be efficient and the demands for performance-based service are changing how nephrologists deliver care. Chronic kidney disease (CKD) occurs in patients with complex medical and social problems. CKD management requires that multidisciplinary professionals provide patient education, disease management, and psychosocial support. To remain cost-efficient, many physicians are training and supervising midlevel practitioners in the delivery of specialized health care. Specialized care that meets present CKD patient needs is best delivered in a CKD clinic. Three models of CKD clinic are identified: (1) anemia management CKD clinic, (2) the basic CKD clinic, and (3) the comprehensive CKD clinic. Each clinic model is based on critical elements of staffing, billable services, and patient-focused health care. Billable services are anemia-management services, physician services that may be provided by midlevel practitioners, and medical nutrition therapy. In some cases, social worker services may be billable. Building a patient-focused clinic that offers CKD management requires planning, familiarity with federal regulations and statutes, and skillful practitioners. Making services cost-efficient and outcome oriented requires careful physician leadership, talented midlevel practitioners, and billing professionals who understand the goals of the CKD clinic. As Medicare payment reforms evolve, a well-organized CKD program can be well poised to meet the requirements of payers and congressional mandates for performance-based purchasing.     

Prevalence of chronic kidney disease in the Japanese general population

Background

We previously estimated the prevalence of chronic kidney disease (CKD) stages 3–5 at 19.1 million based on data from the Japanese annual health check program for 2000–2004 using the Modification of Diet in Renal Disease (MDRD) equation multiplied by the coefficient 0.881 for the Japanese population. However, this equation underestimates the GFR, particularly for glomerular filtration rates (GFRs) of over 60 ml/min/1.73 m². We did not classify the participants as CKD stages 1 and 2 because we did not obtain proteinuria data for all of the participants. We re-estimated the prevalence of CKD by measuring proteinuria using a dipstick test and by calculating the GFR using a new equation that estimates GFR based on data from the Japanese annual health check program in 2005.

Methods

Data were obtained for 574,024 (male 240,594, female 333,430) participants over 20 years old taken from the general adult population, who were from 11 different prefectures in Japan (Hokkaido, Yamagata, Fukushima, Tochigi, Ibaraki, Tokyo, Kanazawa, Osaka, Fukuoka, Miyazaki and Okinawa) and took part in the annual health check program in 2005. The glomerular filtration rate (GFR) of each participant was computed from the serum creatinine value using a new equation: GFR (ml/min/1.73 m²) = 194 × Age^?0.287 × S-Cr^?1.094 (if female × 0.739). The CKD population nationwide was calculated using census data from 2005. We also recalculated the prevalence of CKD in Japan assuming that the age composition of the population was same as that in the USA.

Results

The prevalence of CKD stages 1, 2, 3, and 4 + 5 were 0.6, 1.7, 10.4 and 0.2% in the study population, which resulted in predictions of 0.6, 1.7, 10.7 and 0.2 million patients, respectively, nationwide. The prevalence of low GFR was significantly higher in the hypertensive and proteinuric populations than it was in the populations without proteinuria or hypertension. The prevalence rate of CKD in Japan was similar to that in the USA when the Japanese general population was age adjusted to the US 2005 population estimate.

Conclusion

About 13% of the Japanese adult population—approximately 13.3 million people—were predicted to have CKD in 2005.