Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.
There are few studies evaluating exercise in the nondialysis chronic kidney disease (CKD) population. This review covers the rationale for exercise among patients with CKD not requiring dialysis and the effects of exercise training on physical functioning, progression of kidney disease, and cardiovascular risk factors. In addition, we address the issue of the risk of exercise and make recommendations for implementation of exercise in this population.
Evidence from uncontrolled studies and from small randomized controlled trials shows that exercise training results in improved physical performance and functioning among patients with CKD. In addition, although there are no studies examining cardiovascular outcomes, several studies suggest that cardiovascular risk factors such as hypertension, inflammation, and oxidative stress, may be improved with exercise training in this population. Although the current literature does not allow for definitive conclusions about whether exercise training slows the progression of kidney disease, no study has reported worsening of kidney function as a result of exercise training. In the absence of guidelines specific to the CKD population, recent guidelines developed for older individuals and patients with chronic disease should be applied to the CKD population.
In sum, exercise appears to be safe in this patient population if begun at moderate intensity and increased gradually. Indeed, the evidence suggests that the risk of remaining inactive is higher. Patients should be advised to increase their physical activity when possible and referred to physical therapy or cardiac rehabilitation programs when appropriate.
INTRODUCTION AND OBJECTIVE:
Kidney disorders can cause essential hypertension, which can subsequently cause renal disease. High blood pressure is also common among those with chronic kidney disease; moreover, it is a well-known risk factor for a more rapid progression to kidney failure. Because hypertension and kidney function are closely linked, the present study aimed to observe the beneficial effects of low-intensity physical activity on structural and ultrastructural renal morphology and blood pressure in normotensive and spontaneously hypertensive rats.
Male Wistar-Kyoto rats and spontaneously hypertensive rats were randomly allocated into four groups: sedentary or exercised Wistar-Kyoto and sedentary or exercised spontaneously hypertensive rats. The exercise lasted 20 weeks and consisted of treadmill training for 1 hour/day, 5 days/week.
The exercised, spontaneously hypertensive rats showed a significant blood pressure reduction of 26%. The body masses of the Wistar-Kyoto and spontaneously hypertensive strains were significantly different. There were improvements in some of the renal structures of the animals treated with physical activity: (i) the interdigitations of the proximal and distal convoluted tubules; (ii) the basal membrane of the proximal and distal convoluted tubules; and (iii) in the basal membrane, slit diaphragm and pedicels of the glomerular filtration barrier. The spontaneously hypertensive rats also showed a decreased expression of connexin-43.
Physical exercise could be a therapeutic tool for improving kidney ultrastructure and, consequently, renal function in hypertensive individuals.
Hypertension; Physical activity; Kidney; SHR; Ultrastructure
There are counterintuitive but consistent observations that African American maintenance dialysis patients have greater survival despite their less favorable socioeconomic status, high burden of cardiovascular risks including hypertension and diabetes, and excessively high chronic kidney disease prevalence. The fact that such individuals have a number of risk factors for lower survival and yet live longer when undergoing dialysis treatment is puzzling. Similar findings have been made among Israeli maintenance dialysis patients, in that those who are ethnically Arab have higher end-stage renal disease but exhibit greater survival than Jewish Israelis. The juxtaposition of these two situations may provide valuable insights into racial/ethnic-based mechanisms of survival in chronic diseases. Survival advantages of African American dialysis patients may be explained by differences in nutritional status, inflammatory profile, dietary intake habits, body composition, bone and mineral disorders, mental health and coping status, dialysis treatment differences, and genetic differences among other factors. Prospective studies are needed to examine similar models in other countries and to investigate the potential causes of these paradoxes in these societies. Better understanding the roots of racial/ethnic survival differences may help improve outcomes in both patients with chronic kidney disease and other individuals with chronic disease states.
Cardiovascular disease (CVD) is increasingly recognised as a complication of childhood chronic kidney disease (CKD) even in the absence of diabetes and hypertension. We hypothesized that an alteration in angiopoietin-1 and -2, growth factors which regulate endothelial and vascular function could be involved. We report that the endothelial survival factor, angiopoietin-1 is low in children with pre-dialysis CKD whereas the pro-inflammatory angiopoietin-2 is elevated in children on dialysis. In dialysis patients, angiopoietin-2 positively correlated with time on dialysis, systolic blood pressure, and carotid artery intima media thickness. Elevated angiopoietin-2 levels in dialysis versus pre-dialysis CKD patients were also associated with an anti-angiogenic (high soluble VEGFR-1 and low VEGF-A) and pro-inflammatory (high urate, E-selectin, P-selectin and VCAM-1) milieu. Ang-2 was immunodetected in arterial biopsy samples whilst the expression of VEGF-A was significantly downregulated in dialysis patients. Serum urate correlated with angiopoietin-2 levels in dialysis patients and addition of uric acid was able to induce rapid release of angiopoietin-2 from cultured endothelial cells. Thus, angiopoietin-2 is a marker for cardiovascular disease in children on chronic dialysis and may act as an anti-angiogenic and pro-inflammatory effector in this context. The possibility that the release of angiopoietin-2 from endothelia is mediated by urate should be explored further.
With the increasing prevalence of hypertension, there has been a growing interest in understanding the health-related quality of life (HRQOL) of patients with hypertension. Although hypertension is often perceived as asymptomatic, it is associated with impaired HRQOL due to complications or co-morbidities, awareness of the diagnosis and adverse effects from anti-hypertensive medications. This article focuses on the literature published since 2000, on HRQOL in elderly hypertensive individuals as well as hypertensives with co-existent diseases, including chronic kidney disease (CKD), cardiovascular disease and diabetes mellitus. Most of the studies found that hypertensive individuals with co-existent co-morbidities tend to have lower HRQOL than those with hypertension alone, and identified the number of co-morbid illnesses as an independent determinant of HRQOL. The most pronounced effect was noted in the physical function domains of HRQOL. Studies have also examined the effects on HRQOL of specific classes of antihypertensive drugs without specific demonstration of superiority of 1 drug class over another in terms of HRQOL measures. While there is evidence in favor of ACE-inhibition for improving renal and cardiovascular outcomes in hypertensive patients, its role in ameliorating HRQOL outcomes remains to be established.
Hypertension; quality of life; chronic kidney disease; aging; cardiovascular diseases; diabetes mellitus
Numerous studies have documented the presence of racial disparities among Americans in health outcomes with respect to cardiovascular disease, infant mortality, cancer, and kidney disease. With regard to kidney diseases, these disparities are more dramatic. African, Hispanic, and Native Americans have the highest risks of end-stage renal disease (ESRD). The incidence of ESRD is four times higher in African Americans than in whites. Diseases causing chronic kidney failure, such as diabetes mellitus, hypertension, systemic lupus erythematosus, and human immunodeficiency virus-associated nephropathy, are particularly prevalent among African-American patients. In addition to the higher prevalence, the morbidity associated with kidney complications of these diseases appears worse in African-American patients. African Americans also have worse outcomes and a relatively reduced access to kidney transplantation--the best therapy for ESRD. It is highly likely that social and environmental factors play a very significant role in the persistence of these disparities. A detailed understanding of these socioeconomic and environmental factors will be critical in formulating rational public health strategies to redress these disparities. This paper reviews the social, economic and environmental factors that impact on the incidence of ESRD in minority groups.
Objectives: Scientific literature indicates that the risk of coronary heart disease morbidity and death among peritoneal dialysis patients exceeds risk observed in non-renal patients. The aims of this study were to establish the independent predictors associated with increased risk of coronary heart disease in peritoneal dialysis patients without diabetic nephropathy.
Materials and Methods: A number of 116 end-stage renal disease patients without diabetic nephropathy undergoing peritoneal dialysis were evaluated for coronary heart disease and predictive risk factors were investigated and identified. Also intima-media thickness measurements, as an early sign of atherosclerosis, were analyzed in a subset of patients in correlation with a number of traditional and non-traditional cardiovascular risk factors.
Results: The study sample was found to be characterized by a high prevalence of traditional risk factors: hypertension (95.7%), dyslipidemia (93.1%) and metabolic syndrome (58.6%), but also of dialysis-related risk factors: inflammation (82.8%) and anemia (55.2%). Independent variables found to be associated in regression analysis with coronary heart disease were: age, smoking status, nephroangiosclerosis, albumin, C-reactive protein and iPTH levels. Intima-media thickness was significantly higher in patients with coronary heart disease, values greater than 0.89 mm being associated with increased risks for coronary heart disease, acute coronary syndrome and cardiovascular death.
Conclusions: The prevalence of traditional cardiovascular risk factors in these peritoneal dialysis patients is extremely high, but there are also some other factors involved, especially malnutrition and inflammation. Age higher than 55 years, smoking, albumin less than 3.5 g/dl, iPTH less than 150 pg/ml and nephroangiosclerosis were associated with highest odds ratio for coronary heart disease. An increasing CRP levels was associated with an increasing gradient for coronary heart disease risk.
end-stage renal disease; coronary heart disease; peritoneal dialysis; intima-media thickness
Advances in the field of kidney transplantation have led to a significant increase in the life of renal allograft with 1 - year graft survival rates of 93% to 99%.This increase in early graft survival has made it possible to observe the long-term morbidities that accompany renal transplantation.
Studies correlating the reduction of arterial blood pressure with patient and graft survival as well as the risk of cardiovascular disease do not exist. The recommendations come from the general population and from comparative studies of hypertensive and normotensive kidney graft recipients. It is known that in the general population hypertension is a risk factor for chronic kidney disease but at the same time a risk factor for death, ischaemic heart disease, chronic heart failure and left ventricular hypertrophy. We must always have in mind that there are many similarities between a kidney graft recipient and a patient with chronic kidney disease. Renal transplant recipients represent a patient population with a very high risk for development of cardiovascular disease which has been identified as the leading cause of death in these patients1. Of 18,482 deaths among renal allograft recipients, 38% had functioning renal allografts 2, 3. Successful renal transplantation (Rt) can result in partial regression of left ventricular hypertrophy (LVH) if it is associated with hypertension (HTN) remission or if HTN is controlled by medications. Frequently post transplant HTN is associated with failure of LVH to regress. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit from renal allograft and cardiovascular perspective. The target must always be long term patient and graft survival and acceptable quality of life. The antihypertensive drugs usually used after kidney transplantation are diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β – blockers. Most emphasis is given lately to ACEIs/ARBs and β – blockers because of their cardioprotecive effect.
kidney transplantation; hypertension; anti - hypertensive agents
Hypertension is an important independent risk factor for renal disease. If hypertension and chronic renal disease co-exist, as is common in patients with diabetes mellitus, the risk of cardiovascular disease is heightened. The importance of rigorous blood pressure control is recognized in current guidelines, with a recommended target of office blood pressure of < 130/80 mmHg; although ambulatory blood pressure may be more appropriate in order to identify the 24-hour hypertensive burden. Even lower blood pressure may further reduce the progression of chronic kidney disease, but the incidence of cardiovascular events may increase. Albuminuria not only indicates renal damage, but is also a powerful predictor of cardiovascular morbidity and mortality at least in patients with high cardiovascular risk and potentially pre-existing vascular damage. Management of the multiple factors for renal and cardiovascular disease is mandatory in the diabetic patient. The renin-angiotensin system (RAS) plays a pivotal role in the progression of renal disease, as well as in hypertension and target-organ damage. The use of agents that target the RAS confer renoprotection in addition to antihypertensive activity. There is extensive evidence of the renoprotective effect of angiotensin II receptor blockers (ARBs), and specifically telmisartan. In addition to providing 24-hour blood pressure control, clinical studies in patients with diabetes show that telmisartan improves renal endothelial function, prevents progression from microalbuminuria to macroalbuminuria, slows the decline in glomerular filtration rate and reduces proteinuria in overt nephropathy. These effects cannot be solely attributed to blood pressure control. In contrast to other members of the ARB class, the renoprotective effect of telmisartan is not confined to the management of diabetic nephropathy; slowing the progression of albuminuria has been demonstrated in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET®), which included diabetic and non-diabetic patients at high risk of cardiovascular events.
Patients with chronic kidney disease progress to end stage renal disease and about 86% are diagnosed hypertensives. Hypertension is a risk factor for cardiovascular disease which is the main cause of morbidity and mortality in the dialysis population. Pre and post–dialysis blood pressure values of < 140/90 mmHg are recommended as the optimal blood pressure. The extra-cellular volume (ECV) expansion is the main pathophysiological determinant of hypertension in dialysis patients. The efforts should be made to correctly estimate and achieve the patients dry body weigh and to limit dietary sodium intake. Angiotensin II receptor antagonists, beta blockers and calcium channel blockers are recommended as first choice drugs. Beta blockers and calcium channel blockers have been associated with reduced cardiovascular mortality and give their protective effects in patients at high risk. Antihypertensive drug therapies can effectively reduce blood pressure and are needed by the vast majority of hemodialysis patients.
hypertension; hemodialysis; peritoneal dialysis; cardiovascular disease
The elderly are the most rapidly growing population group in the world. Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. The risk of coronary artery disease, stroke, congestive heart disease, chronic kidney insufficiency and dementia is also increased in this subgroup of hypertensives. Hypertension in the elderly patients represents a management dilemma to cardiovascular specialists and other practioners. During the last years and before the findings of the Systolic Hypertension in Europe Trial were published, the general medical opinion considered not to decrease blood pressure values similarly to other younger patients, in order to avoid possible ischemic events and poor oxygenation of the organs (brain, heart, kidney). The aim of this review article is to highlight the importance of treating hypertension in aged population in order to improve their quality of life and lower the incidence of the cardiovascular complications.
Hypertension; Elderly; Pathophysiology; Treatment
As a result of altered kidney physiology, the aging kidney is at increased risk for both acute and chronic kidney injury. When coupled with the higher prevalence of such comorbid conditions as hypertension, diabetes and cardiovascular disease, it is not surprising that both the incidence and prevalence of chronic kidney disease, including end-stage renal disease (ESRD), increases with age. Although the increase in ESRD with age is observed for all races, it is disproportionately high among ethnic minority populations. The reasons for this are varied and numerous, and a complex interplay of environmental, socioeconomic, cultural, and possibly genetic factors, may be involved. It is clear, therefore, that kidney disease in the elderly ethnic minority population is a cause for specific concern and that targeted strategies are needed to improve disease management and treatment outcomes in this high-risk group of patients.
Chronic kidney disease affects one in nine Americans. Diabetes and hypertension account for nearly three quarters of all kidney failure cases. Disproportionate rates of chronic kidney disease, diabetes, and hypertension have been observed among African Americans. More than 70% of all kidney failure cases caused by diabetes and hypertension could have been prevented or delayed with healthy lifestyles and medications.
Approximately 14% of the population living in Michigan is African American. Despite this small proportion, 47% of patients on dialysis and 45% of those on the kidney transplant waiting list are African American. Risk of end-stage kidney failure is 4 times greater among African Americans than among whites.
The National Kidney Foundation of Michigan developed the Healthy Hair Starts with a Healthy Body (Healthy Hair) campaign to educate African American men and women about their disease risks and to motivate prevention behaviors. The campaign trains African American hair stylists to promote healthy behaviors with their clients through a "health chat" and by providing diabetes and hypertension risk assessment information and incentives.
Since 1999, Healthy Hair has trained nearly 700 stylists and reached more than 14,000 clients in eight Michigan cities. Information collected through a client "Chat Form" suggests a number of positive behavioral results.
With nearly 60% of clients indicating that they have taken steps to prevent diabetes, hypertension, and chronic kidney disease or to seek a physician's advice, the Healthy Hair program appears to be effective in the short term in prompting attention to healthy behaviors and increasing risk awareness.
Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV.
We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease.
PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function.
The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure.
Chronic kidney disease has serious implications with a high risk for progressive loss of renal function, increased cardiovascular events as well as a substantial financial burden. The renin-angiotensin-aldosterone system (RAAS) is activated in chronic kidney disease, especially in diabetes and hypertension, which are the leading causes of chronic kidney disease. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease the rate of progression of diabetic and non-diabetic nephropathy and are recommended therapy for chronic kidney disease.
Key clinical trials supporting the use of ACE inhibitors and ARBs in chronic kidney disease are discussed. Recent developments in our understanding of RAAS biology and the use of direct renin inhibition are reviewed in the context of their potential impact on the prevention and management of chronic kidney disease.
Despite the clinical success of ACE inhibitors and ARBs the rates of mortality and progression to renal failure remain high in these patient populations. ACE inhibitor or ARB monotherapy, in doses commonly used in clinical practice does not result in complete suppression of the RAAS. Aliskiren, a direct renin inhibitor, offers a novel approach to inhibit the RAAS in chronic kidney disease.
High dose ARB therapy or combination therapies with ACE inhibitors and ARBs have shown beneficial effects on surrogate markers of chronic kidney disease. Early data based on urinary protein excretion rates as a surrogate marker for renal function suggest a possibly novel role for aliskiren alone or in combination with ARBs in chronic kidney disease.
Aliskiren; Renin; Angiotensin; Kidney disease
Hypertension is a common and important modifiable risk factor for cardiovascular and kidney diseases. The prevalence of hypertension, particularly isolated systolic hypertension, increases with advancing age, and this is partly due to the age-related changes in the arterial tree, leading to an increase in arterial stiffness. Therapeutic lifestyle changes, such as reduced dietary sodium intake, weight loss, regular aerobic activity, and moderation of alcohol consumption, have been shown to benefit elderly patients with hypertension. Lowering blood pressure (BP) using pharmacological agents reduces the risk for cardiovascular morbidity and mortality, with no difference in risk reduction in elderly patients compared to younger hypertensives. Guidelines recommend a BP goal of <140/90 in hypertensive patients regardless of age and <130/80 in patients with concomitant diabetes or kidney disease, and lowering the BP further has not been shown to confer any additional benefit. Moreover, the choice of antihypertensive does not seem to be as important as the degree of BP lowering. Special considerations in the treatment of elderly hypertensive patients include cognitive impairment, dementia, orthostatic hypotension, and polypharmacy.
hypertension; elderly; treatment; blood pressure
The world’s population is aging, with the number of older adults projected to increase dramatically over the next two decades. This trend poses major challenges to health care systems, reflecting the greater healthcare utilization by and more comorbid conditions among elderly adults. Chronic kidney disease (CKD) is a substantial concern in the elderly, with both an increasing incidence of treated kidney failure with dialysis as well as a high prevalence of earlier stages of CKD. Given the high burden of risk factors for CKD, the high prevalence of CKD in the elderly is not surprising, with the rise in obesity, diabetes and hypertension in middle-aged adults likely foreshadowing further increases in CKD prevalence among the elderly. It is now commonly agreed that the presence of CKD identifies a higher risk state in the elderly, with increased risk for multiple adverse outcomes, including kidney failure, cardiovascular disease, cognitive impairment, and death. Accordingly, CKD in older adults is worthy of attention by both health care providers and patients, with the presence of a reduced GFR or albuminuria in the elderly potentially informing therapeutic and diagnostic decisions for these individuals.
Chronic kidney disease; elderly; glomerular filtration rate; albuminuria; cardiovascular disease
Arterial hypertension is the most prevalent risk factor associated with increased cardiovascular morbidity and mortality. Although pharmacological treatment is generally well tolerated, 5%–20% of patients with hypertension are resistant to medical therapy, which is defined as blood pressure above goal (>140/90 mmHg in general; >130–139/80–85 mmHg in patients with diabetes mellitus; >130/80 mmHg in patients with chronic kidney disease) despite treatment with ≥3 antihypertensive drugs of different classes, including a diuretic, at optimal doses. These patients are at significantly higher risk for cardiovascular events, in particular stroke, myocardial infarction, and heart failure, as compared with patients with nonresistant hypertension. The etiology of resistant hypertension is multifactorial and a number of risk factors have been identified. In addition, resistant hypertension might be due to secondary causes such as primary aldosteronism, chronic kidney disease, renal artery stenosis, or obstructive sleep apnea. To identify patients with resistant hypertension, the following must be excluded: pseudo-resistance, which might be due to nonadherence to medical treatment; white-coat effect; and inaccurate measurement technique. Activation of the sympathetic nervous system contributes to the development and maintenance of hypertension by increasing renal renin release, decreasing renal blood flow, and enhancing tubular sodium retention. Catheter-based renal denervation (RDN) is a novel technique specifically targeting renal sympathetic nerves. Clinical trials have demonstrated that RDN significantly reduces blood pressure in patients with resistant hypertension. Experimental studies and small clinical studies indicate that RDN might also have beneficial effects in other diseases and comorbidities, characterized by increased sympathetic activity, such as left ventricular hypertrophy, heart failure, metabolic syndrome and hyperinsulinemia, atrial fibrillation, obstructive sleep apnea, and chronic kidney disease. Further controlled studies are required to investigate the role of RDN beyond blood pressure control.
resistant hypertension; secondary hypertension; sympathetic nervous system; renal denervation; symplicity
Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS) leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD). Albuminuria is a major risk factor for cardiovascular diseases (CVDs). Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.
Heart failure is common and is associated with poor prognosis. Chronic kidney disease is common in heart failure, and shares many risk factors with heart failure such as age, hypertension, diabetes, and coronary artery disease. Over half of all heart failure patients may have moderate to severe chronic kidney disease. The presence of chronic kidney disease is associated with increased morbidity and mortality, yet it is also associated with underutilization of evidence-based heart failure therapy that may reduce morbidity and mortality. Understanding the epidemiology and outcomes of chronic kidney disease in heart failure is essential to ensure proper management of these patients.
Heart failure; chronic kidney disease; epidemiology; risk factors; management
Patients with chronic kidney disease (CKD) experience co-morbid illneses including cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between retinopathy and self reported CVD in a subgroup of the participants of the Chronic Renal Insufficiency Cohort (CRIC) study. In this observational, ancillary investigation, 2605 CRIC participants were invited to participate in this study, and non-mydriatic fundus photographs in both eyes were obtained in 1936 subjects. Photographs were reviewed in a masked fashion at a central photograph reading center. Presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter caliber were assessed using standard protocols by trained graders masked to information about study participants. History of self-reported cardiovascular disease was obtained using a medical history questionnaire. Kidney function measurements, traditional and non-traditional risk factors for CVD were obtained from the CRIC study. Greater severity of retinopathy was associated with higher prevalence of any cardiovascular disease and this association persisted after adjustment for traditional risk factors for CVD. Presence of vascular abnormalities usually associated with hypertension was also associated with increased prevalence of CVD. We found a direct relationship between CVD prevalence and mean venular caliber. In conclusion, presence of retinopathy was associated with CVD, suggesting that retinovascular pathology may be indicative of macrovascular disease even after adjustment for renal dysfunction and traditional CVD risk factors. This would make assessment of retinal morphology a valuable tool in chronic kidney disease studies of CVD outcomes.
Retinopathy; chronic kidney disease; cardiovascular disease
Chronic kidney disease is becoming a major health problem globally and in India an alarming number of about 8 million people are suffering from this disease. Patients undergoing hemodialysis have a high prevalence of protein-energy malnutrition and inflammation. As these two conditions often occur concomitantly in hemodialysis patients, they have been referred together as ‘malnutrition-inflammation-atherosclerosis syndrome’ to emphasize the important association with atherosclerotic cardiovascular disease. The three factors related to the pathophysiology in these patients are dialysis related nutrient loss, increased protein catabolism and hypoalbuminemia. Inflammation in Chronic Kidney disease is the most important factor in the genesis of several complications in renal disease. Pro-inflammatory cytokines like IL-1 and TNF-alpha play a major role in the onset of metabolic alterations in Chronic Kidney disease patients. Atherosclerosis is a very frequent complication in uremia due to the coexistence of hypertension, hyperhomocysteinemia, inflammation, malnutrition and increased oxidative stress, generation of advanced glycation end products, advanced oxidation protein products, hyperlipidemia and altered structural and functional ability of HDL. LDL-cholesterol, apolipoprotein (A), apolipoprotein (B), and Lp(a) are also associated with atherosclerosis. Studies have now provided enormous data to enable the evaluation of the severity of malnutrition-inflammation-atherosclerosis syndrome as well as effective monitoring of these patients.
Chronic Kidney Disease; Hemodialysis; Malnutrition; Inflammation; Atherosclerosis; Syndrome
Purpose of review
Coronary artery disease is the major cause of death worldwide. Hypertension is a major risk factor for developing coronary disease. It is now recognized that endothelial dysfunction is an early marker of coronary artery disease before structural changes to the vessel wall are apparent on angiography or intravascular ultrasound and that it has a prognostic value in predicting cardiovascular events in hypertensive patients. This review addresses recent developments in hypertension-induced endothelial dysfunction.
Hyperaldosteronism causes endothelial dysfunction independent of high blood pressure. Exaggerated exercise blood pressure response has been related to endothelial dysfunction. Cyclosporin-A-induced endothelial dysfunction is related to reduced cholesterol content in caveolae. Chronic kidney disease induces changes in caveoli-1 and thus contributes to the reduced nitric oxide bioavailability, and causes oxidative stress independent of the high blood pressure. Asymmetric dimethylarginine plays a role in endothelial dysfunction in hypertensive patients independent of insulin resistance. 20-Hydroxyeicosatetraenoic acid is an independent predictor of hypertension in postmenopausal women. Endothelial dysfunction precedes and predicts the development of hypertension in postmenopausal women. Oral treatment with L-arginine improves endothelial dysfunction in hypertensives and lowers the blood pressure.
The pathophysiology of endothelial dysfunction in hypertension is multifactorial. Recent findings have contributed to our understanding of mechanisms of endothelial dysfunction and support a role for early intervention to prevent irreversible vascular and organ damage.
coronary artery disease; endothelial dysfunction hypertension; nitric oxide
Diabetic kidney disease is characterized by persistent albuminuria (>300 mg/dl or >200 μg/min) that is confirmed on at least 2 occasions 3 to 6 months apart, with a progressive decline in the glomerular filtration rate (GFR), elevated arterial blood pressure, and an increased risk for cardiovascular morbidity and mortality. Diabetic kidney disease is the leading cause of end stage renal disease (ESRD) prompting investigators to evaluate mechanisms by which to slow disease progression. One such mechanism is to block the activity of angiotensin II at the receptor site and agents that follow this mechanism are referred to as angiotensin receptor blockers (ARB). There is sufficient clinical evidence to support that ARB have protective effects on kidney function in patients with diabetes and hypertension. However, in the past decade there have been few investigations comparing individual ARBs on renal outcomes. Telmisartan, a lipophilic ARB with a long half-life, has been hypothesized to have a greater anti-proteinuric effect when compared to the shorter acting losartan. Therefore, the A comparison of telMisartan versus losArtan in hypertensive type 2 DiabEtic patients with Overt nephropathy (AMADEO) trial sought to investigate renal and cardiovascular endpoints. In this review, we discuss the pathophysiology of diabetic kidney disease and implications of the AMADEO trial in the context of current understanding from recent outcome trials.
diabetic kidney disease; hypertension; telmisartan; AMADEO