Hypertension and kidney disease: A deadly connection

Kidney disease may be the cause or a consequence of hypertension. Hypertension affects 25% of the adult population in the United States. Similarly, chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been steadily increasing in incidence because of the increasing age of the US population and rise in the incidence of risk factors, including hypertension. Substantial evidence supports the notion that elevated blood pressure is the most significant risk factor for the development of CKD. Microalbuminuria has been shown to be the early marker of hypertensive renal disease. Furthermore, therapy to reduce microalbuminuria was associated with delay in the progression of renal disease. Black Americans are at higher risk for developing hypertensive nephrosclerosis than whites. Hypertension is a major risk factor for cardiovascular events in patients with CKD and ESRD and those who have undergone renal transplantation. Studies have documented that elevated serum creatinine and CKD are risk factors for a cardiovascular event. Tight blood pressure control has been shown to reduce microalbuminuria and proteinuria and to delay progression of renal disease. Tailoring the choice of antihypertensive medication to the clinical setting to achieve a blood pressure goal is critical in reducing complications from this deadly connection.     

Hypertension management: Special considerations in chronic kidney disease patients

It has been estimated that approximately 11% of the US adult population has chronic kidney disease (CKD), and it has been demonstrated that the prevalence of hypertension rises significantly as renal function declines. Even mild CKD significantly increases mortality risk, and cardiovascular disease remains the main cause of death among these patients. Although CKD patients have generally been excluded from trials testing the effect of lowering blood pressure on cardiovascular outcomes, guidelines suggest lowering blood pressure in hopes of reducing cardiovascular mortality and slowing the progression of renal disease. The preferred antihypertensive agents among these patients are drugs that block the renin-angiotensin system. In most hypertensive CKD patients, however, multiple agents are necessary to reach blood pressure targets. In general, diuretics and calcium channel blockers are added subsequently as adjunctive therapy. Hopefully, with increased recognition of the unique aspects of treating hypertension in this population, end-stage renal disease and cardiovascular morbidity and mortality will be delayed or avoided in the millions of patients with CKD.     

Ambulatory blood pressure and the kidney

During the last few years there has been a renewed interest in blood-pressure-induced kidney damage, due to a progressive increase in the incidence and prevalence of hyipertension and vascular diseases as a cause of end-stage renal disease (ESRD). The need to prevent ESRD demands continued efforts to achieve the early identification of persons with hypertension who are at risk and to provide them with effective antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) has been used successfully to assess blood pressure values and identify risk markers for cardiovascular diseases. A logical approach would be to use it also to identify those for ESRD. For hypertensive and type 1 diabetics ABPM data usually have a stronger correlation to the presence and magnitude of microalbuminuria than do routine office blood pressure measurements. The best Pearson correlation coefficients for relationship between ambulatory blood pressure values and urinary excretion of albumin were obtained with nocturnal blood pressure regardless of whether systolic, diastolic or mean blood pressure were considered. Moreover, high percentages of non-dippers have been found among subjects with renal failure, subjects undergoing dialysis (haemofiltration, peritoneal dialysis, continuous ambulatory peritoneal dialysis (CAPD), subjects with renovascular hypertension and with cystic kidney disease, subjects who have had a kidney transplant and subjects with cyclosporine-induced hypertension. Finally, ABPM seems to be prognostic for development of proteinuria in some refractory hypertensives. Whether higher nocturnal blood pressure values and the non-dipping pattern constitute a cause or are consequences of renal disease should be addressed in prospective studies. Assessment of nocturnal blood pressure seems to be an important tool in the management of patients with hypertensive-related renal disease and of patients who are susceptible to developing it.     

The effect of blood pressure reduction on end stage renal disease

In the past 20 years, clinicians have clearly demonstrated that antihypertensive therapy is very effective in reducing the incidence of myocardial infarction and stroke. However, little is known about the effects of blood pressure reduction on end stage renal disease (ESRD). Data from major clinical studies has clearly shown that patients with hypertension have an increased risk of developing ESRD. Black men and women with hypertension are at the greatest risk; however, the incidence of ESRD is increasing in all racial groups. Because patients with hypertensive ESRD often require dialysis, the cost of treating this increasing common disorder has the potential to deplete the Medicare system. The primary effect of blood pressure reduction in patients with ESRD has not been adequately addressed in any trial that has been completed to date. Results from some studies suggest that blood pressure reduction may improve renal function and that angiotensin converting enzyme inhibitors and calcium channel blockers may have renoprotective effects. Currently in progress are two large scale clinical trials that may provide more information on the effects of antihypertensive therapy on preventing ESRD in hypertensive patients. These are the African American Study of Kidney Disease and Hypertension (AASK), and a substudy of the Hypertension Optimal Treatment (HOT) Study. Data from the HOT study is expected to be available 5 years prior to that of the ASK Study, which is expected to be completed by the year 2002.     

Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease

Abstract. Stenvinkel P (Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden). Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease (Review). J Intern Med 2010; 268 : 456–467. The epidemics of cardiovascular disease, obesity, diabetes, HIV and cancer have all received much attention from the public, media and policymakers. By contrast, chronic kidney disease (CKD) has remained largely a ‘silent’ epidemic. This is unfortunate because early diagnosis of renal disease based on proteinuria and/or reduced estimated glomerular filtration rate could enable early intervention to reduce the high risks of cardiovascular events, end‐stage renal disease (ESRD) and death that are associated with CKD. Given the global increase in the incidence of the leading causes of CKD – hypertension, obesity and diabetes mellitus – better disease management and prevention planning are needed, as effective strategies are available to slow the progression of CKD and reduce cardiovascular risk. CKD may be regarded as a clinical model of accelerated vascular disease and premature ageing, and the risk‐factor profile changes during the progression from mild/moderate CKD to ESRD. Although many randomized controlled trials in patients with mild to moderate CKD have shown beneficial effects of interventions aimed at preventing the progression of CKD, most trials have been unable to demonstrate a beneficial effect of interventions aimed at improving outcome in ESRD. Thus, novel treatment strategies are needed in this high‐risk patient group.     

A longitudinal study of hypertension risk factors and their relation to cardiovascular disease: the Strong Heart Study

This study estimated hypertension incidence and explored hypertension risk factors and their association with cardiovascular disease. Data collected from 4549 American Indian participants in the 3 exams of the Strong Heart Study were used. Hypertension was defined as systolic blood pressure > or =140 mm Hg, diastolic blood pressure > or =90 mm Hg, or current use of antihypertensive medication. Generalized linear models were used to identify the risk factors for hypertension and the correlates of blood pressures. Cox proportional models with time-dependent covariates and the mixed models were used to explore the association of hypertension with cardiovascular disease. There was no sex difference in hypertension. After adjustment for other risk factors, the risks of developing hypertension among subgroups in each characterized group were as follows: prehypertensive versus normotensive, 3.21 times; macroalbuminuria and microalbuminuria versus normal, 3.47 and 1.72; diabetic versus nondiabetic, 1.56; overweight and obese versus normal weight, 1.30 and 1.51; and current alcohol drinking versus not, 1.22. Moreover, systolic blood pressure was significantly and positively associated with age, obesity, and albuminuria and negatively with smoking. After adjusting all other risk factors, those pretreated, untreated, controlled, and uncontrolled hypertensive participants had &1.74, 1.81, 2.19, and 2.77 times higher risks of developing cardiovascular disease compared with normotensive participants, respectively. In 45- to 74-year-old American Indians, the risk of developing hypertension was rising. Prehypertensive participants had 3.2/1.74 times higher risk of developing hypertension/cardiovascular disease than normotensive participants. Age, diabetes, and macro/microalbuminuria were independently significant risk factors of both hypertension and cardiovascular disease.     

Proteinuria: an underappreciated risk factor in cardiovascular disease

Changes in renal function produced by hypertension appear to be associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (eg, micro-albuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance, or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. The Framingham Heart Study documented the relevance of proteinuria for cardiovascular prognosis in the community. The International Nifedipine GITS study: Intervention as a goal in Hypertension Treatment (INSIGHT) study assessed the role of proteinuria as a very powerful risk factor. Several studies demonstrated that microalbuminuria is a predictor of cardiovascular disease. It has been shown that the presence of microalbuminuria in primary hypertension carries an elevated cardiovascular risk. Furthermore, recent data indicate that even minor derangements of renal function are associated with an increase in cardiovascular risk factors, and promote progression of atherosclerosis. All these parameters should routinely be evaluated in clinical practice, and in the future must be considered in any stratification of cardiovascular risk in hypertensive patients.     

Treatment of hypertension in patients with nondiabetic chronic kidney disease

Hypertension is highly prevalent in patients with chronic kidney disease (CKD). As either the cause or the consequence of CKD, hypertension is an important independent factor determining the rate of loss of renal function. Hypertension is also a significant independent risk factor for cardiovascular events in patients with CKD, the leading cause of their morbidity and mortality. Based on evidence from observational cohort studies and randomized clinical trials, the Canadian Hypertension Education Program (CHEP) recommends a target blood pressure (BP) of lower than 130/80 mmHg in hypertensive patients with nondiabetic CKD. The CHEP also endorses the use of renin-angiotensin system blockers for the BP-lowering regimen in nondiabetic patients with CKD and significant proteinuria. It is recognized that the majority of nondiabetic patients with CKD will require two or more BP-lowering drugs to attain target BP. Furthermore, extracellular fluid volume expansion is a major contributor to hypertension in patients with CKD, and diuretics should be part of the BP-lowering regimen in the majority of patients. Patients with CKD are recognized to be at high risk for cardiovascular events, and studies testing new emerging treatments of hypertension to reduce the burden of CKD on renal and cardiovascular outcomes are underway. In this regard, the CHEP will continue to review and update all its recommendations annually.     

Chronic kidney disease and cardiovascular risk

Chronic kidney disease (CKD) is a global public health concern, and there is emerging a strong relationship between CKD and increased cardiovascular disease (CVD) risk. CKD in the presence of other co-morbidities such as type 2 diabetes mellitus (T2DM) and hypertension (HTN) can lead to early progression to end-stage renal disease (ESRD/stage V CKD) and confer a greater risk for CVD morbidity and mortality. CVD events are the leading cause of premature death in patients with CKD, even before their progression to ESRD, with the rate of CVD progression being twice as common compared with the general population. The higher mortality from CVD persists even after adjusting for most of the traditional risk factors, suggesting the possible contributions of uremia-related, nontraditional risk factors. This has led to the current understanding that the pathophysiology of CVD in CKD involves a complex interplay of both the traditional as well as nontraditional, uremia-related risk factors. This review will elaborate on the pathophysiology of CVD in CKD and will discuss the role of microalbuminuria (MAU)-proteinuria as a potential diagnostic and prognostic tool for CVD in CKD risk assessment.     

Pathogenesis and Treatment of Microalbuminuria in Patients With Diabetes: The Road Ahead

The incidence of type 2 diabetes is increasing in the United States, which is expected to result in an increased prevalence of microalbuminuria and higher cardiovascular risk. Microalbuminuria is an indication that a low-level inflammatory process is ongoing. In patients with hypertension, with or without diabetes, increasing urinary albumin excretion (UAE) is associated with elevated levels of inflammatory markers, endothelial dysfunction, and platelet activation. Microalbuminuria is associated with an increased incidence of cardiovascular disease (CVD) morbidity and mortality in patients with hypertension and in those with diabetes with or without hypertension. Antihypertensive agents that modulate the renin-angiotensin-aldosterone system (RAAS) can delay the onset and reduce progression of microalbuminuria and decrease CVD morbidity and mortality in patients with diabetes. Clinical trials provide a spectrum of results regarding the protective effects of RAAS-blocking agents. Consideration of baseline blood pressure (BP), UAE and CVD risk, and the extent of BP lowering with treatment is necessary when interpreting clinical trial results in patients with microalbuminuria. It remains to be determined whether targeting the underlying inflammatory process can retard or prevent microalbuminuria progression or whether treatment of microalbuminuria can prevent end-stage renal disease or death.     

Hypertension in chronic kidney disease and dialysis: pathophysiology and management

Hypertension affects 24% of the adult US population. In the United States, 3% of the adult population has an elevated serum creatinine level, and 70% of these patients have hypertension. The prevalence of hypertension in chronic kidney disease (CKD) depends on the patient's age and the severity of renal failure, proteinuria, and underlying renal disease. As patients with CKD progress to end-stage renal disease (ESRD), 86% are diagnosed with hypertension. It has long been recognized that kidney function affects and is affected by hypertension. This article discusses the pathophysiology and management of hypertension in patients with CKD.     

HOW TO PREVENT PROGRESSION TO END STAGE RENAL DISEASE

Chronic kidney disease (CKD) and end stage renal disease (ESRD) are severe medical conditions, increasing threats to human health and socio‐economic burdens in industrialized countries. CKD is assessed by an estimation of the glomerular filtration rate (eGFR). ESRD is an indication for renal replacement therapy by either dialysis or kidney‐transplantation. Major risk factors for CKD are arterial hypertension, hyperglycemia and hyperlipidemia. The multifactorial pathogenesis of CKD and ESRD offers various therapeutic interventions: treatment of the underlying disease, anti‐hypertensive therapy, glycemic control and anti‐diabetic therapy, anti‐proteinuric therapy, renoprotection, and life style management. Angiotensin converting enzyme inhibitors (ACE‐I) and angiotensin II receptor blockers (ARB) lower the systemic blood‐pressure, reduce proteinuria and may slow or even halt the deterioration of renal function. Alert glycemic control is important to avoid or protract diabetic nephropathy. Restricted protein intake, cessation of cigarette smoking and chronic analgesic‐abuse may also prevent the progression of chronic nephropathy.     

Evaluation and treatment of hypertension.

Hypertension is a significant and prevalent risk factor for the development of cardiovascular disease and target organ damage. The urgency of treatment of high blood pressure depends on the level of blood pressure elevation and the presence of coexistent risk factors for cardiovascular disease. Likewise, the level to which blood pressure is reduced is not restricted to the definition of high blood pressure but instead depends on the underlying disease. Diabetes and renal insufficiency, for example, require blood pressure goals below those that are traditionally defined. In the absence of contraindications, beta-blockers and diuretics are still recommended as first-line agents for treatment of uncomplicated hypertension. Calcium channel antagonists also may reduce mortality. In patients with diabetes, ACE inhibitors are effective first-line agents in type 1 and type 2 diabetic patients who are hypertensive or have microalbuminuria. ACE inhibitors may be beneficial in patients with nondiabetic renal insufficiency as well. Calcium channel antagonists may have some effect in retarding progression of diabetic nephropathy although a recent trial found a higher incidence of death as a secondary endpoint in hypertensive diabetic patients who were treated with calcium channel antagonists. Beta-blockers seem to be safe and well tolerated in patients with mild to moderate intermittent claudication, although patients with rest pain or limb ischemia have not been studied. Beta-blockers should not be used in patients with asthma. Dihydropyridine calcium channel antagonists are the preferred treatment of hypertension in patients with Raynaud's but should be avoided in patients with severe gastroesophageal reflux disease. NSAIDs, particularly piroxicam and indomethacin, raise mean blood pressure by approximately 5 mm Hg, enough to consider a change of either NSAID or antihypertensive to one that is not as affected by NSAIDs. Cyclosporine A can induce hypertension by its vasoconstrictive effects, particularly on the kidney. Calcium channel antagonists may antagonize this vasoconstriction while allowing the clinician to reduce the dose of cyclosporine A required to achieve its immunosuppressive effect.     

Epidemiology of hypertensive kidney disease

The prevalence of hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD) attributable to hypertension continues to rise worldwide. Identifying the precise prevalence of CKD attributable to hypertension is difficult owing to the absence of uniform criteria to establish a diagnosis of hypertensive nephropathy. Despite the increasing prevalence of CKD-associated hypertension, awareness of hypertension among individuals with CKD remains suboptimal and rates of blood-pressure control remain poor. Targeted subgroups involved in studies of CKD seem to reach better rates of blood-pressure control, suggesting that this therapeutic goal can be achieved in patients with CKD. Elevated blood-pressure levels are associated with CKD progression. However, the optimal blood-pressure level and pharmacological agent remains unclear. Physicians treating patients with CKD must recognize the importance of maintaining optimal salt and volume balance to achieve blood-pressure goals. Furthermore, agents that modify the renin-angiotensin-aldosterone axis can be an important adjunct to therapy and physicians must monitor expected changes in serum creatinine and electrolyte levels after their administration. Hypertension remains a common factor complicating CKD. Future investigations identifying early signs of hypertension-related CKD, increasing awareness of the effects of hypertension in CKD and determining optimal therapeutic interventions might help reduce the incidence of hypertensive nephropathy.     

Antihypertensive drugs and the kidney

In the United States, 50 million Americans are estimated to have hypertension. Over the past several decades, it has become clear that hypertension is both a cause and a consequence of kidney disease. In contrast to the striking decline in mortality rates from both stroke and coronary heart disease, the prevalence of hypertension as a cause of end-stage renal disease (ESRD) has increased such that it is now the second most common cause of ESRD in the United States. Hypertension and proteinuria occur in most patients with chronic kidney disease and are risk factors for faster progression of kidney disease. Antihypertensive agents reduce blood pressure and urine protein excretion and slow the progression of kidney disease. The level of blood pressure achieved and use of renin-angiotensinaldosterone system-blocking agents is critical for delaying progression of renal disease in all ethnic groups.     

Hypertensive renal vascular disease and cardiovascular endpoints

PURPOSE OF REVIEW: Hypertension involves the entire cardiovascular system, and hypertensive vascular disease may promote and exacerbate cardiac and renal dysfunction. We discuss the coexistence of cardiorenal disease as a manifestation of vascular involvement in hypertension, and the relationship of biomarkers of renal vascular involvement in hypertension with cardiovascular endpoints. RECENT FINDINGS: Markers of renal dysfunction, especially microalbuminuria, have been considered recently as potent predictors of cardiovascular morbidity and mortality in all explored populations, including hypertensive individuals. Microalbuminuria, per se, is related to vascular injury and to the increased glomerular permeability of albumin as a direct manifestation of renal vascular involvement in hypertension, a systemic vascular disease. Left ventricular hypertrophy in hypertension develops even before proteinuria or impairment of renal function. Factors including anemia, inflammation and hyperuricemia are either induced or exacerbated by renal vascular disease, and each of these may exert additional influence in determining the increased incidence of cardiovascular events with progressive renal dysfunction. SUMMARY: The development and progression of vascular disease is the primary determinant in the progressive cardiac and renal dysfunction observed in hypertension and, therefore, is the underlying mechanism of the overall clinical manifestations of cardiorenal disease. Commonly used biomarkers of renal and vascular function are important tools for determination of the progression and, hence, management of hypertensive disease and its complications.     

Management of hypertension in hemodialysis patients

Hypertension is very common in patients with chronic kidney disease and is present in most patients with end-stage renal disease (ESRD). Hypertension is largely responsible for premature cardiovascular disease in dialysis patients. The pathophysiology of hypertension in ESRD is complex, and multiple mechanisms are likely involved in blood pressure dysregulation in patients on hemodialysis. Some of these patients demonstrate resistant hypertension. Aggressive control of hypertension in ESRD/dialysis is mandatory. Generally, nonpharmacologic treatments are not enough to achieve the goal blood pressure levels in dialysis patients. Multiple antihypertensive drugs are often necessary. Drugs that block the reninangiotensin system offer a number of advantages for patients with chronic kidney disease or ESRD, but additional drug classes are often needed to achieve effective blood pressure control in dialysis patients. Physicians treating hypertension in dialysis patients should be familiar with the pharmacokinetic properties of antihypertensive drugs in renal failure and choose the dosages accordingly. Vigorous control of hypertension is recommended to reduce the disease burden in patients with ESRD.     

Is Nocturnal Blood Pressure Reduction the Secret to Reducing the Rate of Progression of Hypertensive Chronic Kidney Disease?

Hypertension is a significant risk factor for cardiovascular and renal disease. Lowering blood pressure (BP) has been shown to reduce the incidence of cardiovascular disease, but randomized trials have not demonstrated a benefit of lowering BP for the progression of renal disease except in secondary analyses in patients with significant proteinuria. Recently, there has been increasing interest in measuring BP outside of the clinic, using both home and ambulatory blood pressure monitoring (ABPM). ABPM has the advantage of measuring BP throughout both the day and night. Elevated nighttime BP and a lack of decline in BP from day to night (nondipping) are more potent risk factors for cardiovascular and renal outcomes than elevated daytime or clinic BP. Studies have shown that it is possible to lower nighttime BP and restore normal dipping with the administration of antihypertensive medications in the evening, known as chronotherapy. Evening administration of antihypertensives not only lowers nighttime BP but also is associated with decreased urinary protein excretion, decreased cardiovascular events, and decreased all-cause mortality. Reducing nighttime BP may slow the progression of chronic kidney disease and may be the key to linking the treatment of hypertension with improved renal outcomes.     

Predictors of renal and cardiovascular mortality in patients with non-insulin-dependent diabetes: A brief overview of microalbuminuria and insulin resistance

Both microalbuminuria and insulin resistance are present at some stage in the natural history of non-insulin-dependent diabetes mellitus (NIDDM). Microalbuminuria predicts both progression to endstage renal disease and an increase in cardiovascular mortality compared to diabetic patients without microalbuminuria. Conversely, microalbuminuria is not a strong predictor of either renal or cardiovascular mortality in hypertensive nondiabetic subjects. This difference in risk may relate to the presence of glycated albumin in patients with diabetes. Glycation of albumin occurs because of persistent hyperglycemia. Glycated albumin is directly toxic to both renal and vascular tissue through stimulation of reactive oxygen species by both renal and immune protective cells. Blunting the rise in microalbuminuria with either aggressive blood glucose control or angiotensin-converting enzyme (ACE) inhibition, early in the course of the disease, markedly reduces renal mortality. In contrast to microalbuminuria, which is a reflection of renal injury, insulin resistance is a genetically determined problem that directly relates to peripheral glucose utilization. In most cases, insulin resistance is phenotypically expressed as diabetes as a result of environmental factors such as obesity. Insulin resistance is associated with an increased risk for development of both hypertension and NIDDM as well as atherosclerosis. Diabetic or hypertensive subjects with insulin resistance have an increased risk of cardiovascular but not renal mortality. Sustained weight loss is the best way to reduce insulin resistance and arterial pressure. Additionally, blockers, more than other antihypertensive agents reduce insulin resistance. This class of drugs, however, has not been shown to reduce either microalbuminuria or overall cardio-renal mortality.     

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??Abstract??The global population is progressively aging??to the extent that over 1.5 billion people worldwide will be aged 65 years or more by 2050.Chronic kidney disease (CKD) in the elderly has become a major public health problem in China with approximately one third to one half of the individuals older than 70 years have CKD.Rates of treated end-stage renal disease (ESRD) among the elderly have been rising dramatically over the last decade.Most of older individuals with CKD die from cardiovascular diseases??infections and cerebrovascular diseases before reaching ESRD.Proteinuria??hypertension??diabetes??hyperlipidemia??and diet are strong risk factors for progression from CKD to ESRD.In this review??we will discuss comprehensive treatment strategy in preventing and slowing progression of CKD in elderly patients concerning the above risk factors.