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.     

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.     

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.     

Cardiovascular disease in early stages of chronic kidney disease in a Chinese population

Cardiovascular disease (CVD) is one of the most serious complications of kidney disease, yet studies of CVD in early stage of chronic kidney disease (CKD) in Asian patients are very limited. Therefore, this study determined the prevalence and the spectrum of CVD in individuals with early-stage CKD and compared them with data of individuals without CKD. Compared with individuals with estimated GFR (eGFR) >90 ml/min per 1.73 m2, the prevalence of myocardial infarction, stroke, and total CVD of individuals with eGFR 60 to 89 ml/min per 1.73 m2 was increased by 91.4, 71.7, and 67.6%, respectively. For individuals with eGFR 30 to 59 ml/min per 1.73 m2, the percentage was 105.2, 289.1, and 200.7%, respectively. For each eGFR category, stroke was more prevalent than myocardial infarction. Compared with individuals with eGFR >90 ml/min per 1.73 m2, participants with eGFR 60 to 89 and 30 to 59 ml/min per 1.73 m2 tended to have more cardiovascular risk factors, and there were strong unadjusted and adjusted associations between CVD with different stages of eGFR (eGFR >90 ml/min per 1.73 m2 as reference). This is the first report on the prevalence and the spectrum of CVD in early stages of CKD in a community-based Chinese population. The spectrum of CVD in this Chinese population is different from reports of Western countries. Individuals with subtle decreased renal function seem much more likely to have multiple cardiovascular risk factors and have higher prevalence of CVD than those without CKD.     

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.     

Long-term risk of chronic kidney disease in unilateral multicystic dysplastic kidney

The clinical spectrum of renal dysplasia includes the non-functioning multicystic dysplastic kidney (MCDK). We report our experience of the outcome of unilateral MCDK and its contralateral kidney in 101 children with the diagnosis of MCDK from 1985 to 2009. Data collected included urine protein/creatinine ratio, estimated GFR (eGFR), blood pressure, surgical intervention, renal length and abnormalities of the contralateral kidney, and the involution rate. There was a predominance of left-sided MCDK. Diagnosis was made prenatally in 86.7%. Contralateral abnormalities included vesicoureteral reflux (16.8%), UPJ obstruction (4.1%), and megaureter (2.4%). Complete involution of MCDK occurred within 5 years in 60%. Compensatory hypertrophy of the contralateral kidney to >97% occurred in 74.1%. Nephrectomy was performed in 19.8%. There was an increased risk of chronic kidney disease (CKD) stage ≥2, and hypertension in those with contralateral abnormalities (p < 0.0001; p < 0.001 respectively). In those without contralateral abnormalities, hyperfiltration with mean eGFR of 149 ± 13 ml/min/1.73 m² was seen in 32% and proteinuria in 9.8%. There was a significantly inverse relationship between proteinuria and eGFR (p < 0.0001). In conclusion, children with contralateral abnormalities are at risk for developing decreased kidney function, whereas a substantial number of patients with no obvious contralateral abnormalities have markers of renal injury. Therefore, systematic follow-up of all patients is recommended.     

Cardiovascular risk factors in kidney transplantation

Classical and non-classical cardiovascular risk factors are common after renal transplantation, and they are effectively associated with the development of cardiovascular disease. Despite the absence of large, controlled clinical trials examining the effect of prevention strategies, therapies should not be withheld from renal transplant recipients with significant risk factors, because their risk of developing cardiovascular disease is at least as high as that of the general population.     

Fracture risk assessment in patients with chronic kidney disease

Fractures are common in patients with chronic kidney disease (CKD) and associated with substantially high morbidity and mortality. Bone mass measurements are commonly used to assess fracture risk in the general population, but the utility of these measurements in patients with CKD, and specifically among those on hemodialysis, is unclear. This review will outline the epidemiology and etiology of fractures in patients with CKD with a particular emphasis on men and women on hemodialysis. As well, we will summarize the published data, which describes the association between risk factors for fracture (including bone mass measurements, biochemical markers of mineral metabolism, and muscle strength) and fractures in patients with CKD. Patients with CKD suffer from fractures due to impairments in bone quantity, bone quality, and abnormalities of neuromuscular function. There is a paucity of evidence on the associations between bone quality, bone turnover markers, neuromuscular function, and fractures in patients with CKD. Furthermore, the complex etiology of fractures combined with the technical limitations of bone mineral density testing, both by dual energy X-ray absorptiometry (DXA) and by peripheral quantitative tomography (pQCT), limits the clinical utility of bone mass measurements for fracture prediction in CKD; this is particularly true among patients with stages 4 and 5 CKD. Further prospective studies to identify noninvasive measures of bone strength that can be used for fracture risk assessment are needed.     

Uremia-related metabolic cardiac risk factors in chronic kidney disease

Growing evidence has been gathered over the last 15 years regarding the role of nontraditional or uremia-related risk factors in the pathogenesis of atherosclerosis in subjects with renal failure. Among those factors, dyslipidemia, inflammation, hyperhomocysteinemia, and oxidant stress have been extensively studied. However, the clinical significance of many of these factors remains controversial in light of reported studies. In this article, the existing evidence regarding the role of uremia-related risk factors in the pathogenesis of atherosclerosis is reviewed, with special emphasis on prevalence, cardiac risk, and management in patients with chronic kidney disease (CKD). Consensus treatment recommendations are provided for risk factors for which there is evidence to support preventive or therapeutic interventions.     

Long-term risk of hypertension and chronic kidney disease in living kidney donors

Objective

The aim of this study was to assess the long-term risks of chronic kidney disease and arterial hypertension in living kidney donors.

Methods

Donors who were followed for more than 1 year after nephrectomy were included. We assessed each donor's blood pressure, urine protein, and estimated glomerular filtration rate (eGFR).

Results

The follow-up rate was 11% (154 out of 1,356 donors), only 19% of whom were followed by nephrologists. Blood pressure had increased from 113/75 to 116/77 mm Hg (P < .01), urinary protein excretion after donation did not increase, and renal function was well preserved after donor nephrectomy. However, 33 patients (21.4%) showed a decreased eGFR of <60 mL/min/1.73 m², and 3 donors developed end-stage renal disease that required renal replacement therapy.

Conclusions

The follow-up rate of living donors after donation was low, and we observed an increased risk of developing chronic kidney disease after donation.