Guest editorial: hypertension and kidney disease

Abstract

In this issue of Advances in Chronic Kidney Disease, a broad spectrum of topics dealing with various aspects of hypertension and chronic kidney disease (CKD) are presented. Peter McCullough and colleagues highlight the fact that presence of CKD is a well-recognized and independent risk factor for cardiovascular disease (CVD) events, including stroke and myocardial infarction. A glomerular filtration rate of less than 60 mL/min or persistent microalbuminuria (<300 mg/g creatinine) are independent markers for increased cardiovascular risk. Estimation of glomerular filtration rate using serum creatinine and demographic factors, including age, gender, and race is now an accepted method of identifying those at risk for CVD events. For this reason, screening for early nephropathy among those with diabetes or hypertension is warranted. A rationale for multiple risk-factor intervention, including pharmacological as well as diet and life-style modifications, for reducing risk of both progression of CKD and development of CVD events is presented.The observations put forth by McCullough et al are further expanded by Yeo and colleagues in patients with stage 4 and 5 nephropathy. People with these stages of nephropathy are at much higher CVD risk than the general population or people with earlier stages of nephropathy. Moreover, people at these stages of nephropathy are not maximally treated to reduce blood pressure or CVD risk. These aspects of risk management and others are discussed.Blood pressure measurement in people on dialysis is challenging, with many unanswered questions. Niranjan Sankaranarayanan and colleagues have been studying this issue for some time and discuss in detail approaches to measurement of blood pressure in people on dialysis. They discuss not only different methodologies but also the role of 24-hour ambulatory measurements compared with routine measurements. They also deal with the troubling questions of when is the best time to measure blood pressure and under what circumstances.In a separate paper, Portman et al highlight the many challenges that face the management of hypertension in children with CKD. It is clear that hypertension in children results from diverse causes, particularly in early years, mostly from secondary forms. However, in older children, primary hypertension is much more common. This timely review indicates that accurate measurement of blood pressure in this vulnerable population includes routine methods, such as automated BP measures, as well as ambulatory blood pressure monitoring. Elevated blood pressure, as determined by either routine or ambulatory BP measurement, is associated with target-organ damage in children. The authors emphasize the need for better techniques to assist in early identification and intervention to reduce risk of subclinical end-organ involvement and for prevention of cardiovascular disease. Future investigations should focus on appropriate workup, criteria for use of potentially invasive and expensive diagnostic techniques, criteria for beginning antihypertensive therapy, and pharmacokinetic and pharmacodynamic properties of antihypertensive agents in children. On this background, questions remain as to the impact of early intervention on prevention of hypertensive complications later in life. Accordingly, the authors conclude that children with hypertension of any etiology should be primarily managed by those with extensive experience in pediatric hypertension and nephrology.In the paper by Ikizler, recent advances in our understanding of the relationships between nutrition and inflammation in the pathogenesis of CKD and its complications are discussed. New data on inflammatory markers in CKD, including C-reactive protein (CRP) and others in relation to nutritional status, morbidity, and mortality in CKD are reviewed. In addition, the role of oxidative stress in the pathogenesis and progression of CKD is discussed in some detail. There is clear evidence that uremic malnutrition and chronic inflammation are important comorbid conditions closely linked to CVD risk in people with ESRD. However, additional studies are needed to establish the pathophysiological link(s) between malnutrition, inflammation, and atherosclerosis in CKD patients. Both uremic malnutrition and chronic inflammation are also associated with increased oxidative stress, a condition proposed as a unifying concept of CVD in uremia. These and related data are discussed by the author. Further research in this area is likely to identify future treatment options to improve the high mortality and morbidity in ESRD patients.Weir discusses treatment and goal blood-pressure values in kidney transplant patients. In this area, as in dialysis, an accepted goal blood pressure, as well as ideal antihypertensive agent to confirm optimal protection, is unknown. Although many surgeons use calcium antagonists, many recent studies with biopsies of the transplanted kidneys suggest that block of the renin-angiotensin system confers greater long-term protection. Additionally, the author discusses the CVD risk associated with different levels of blood pressure in this patient group.In short, all aspects of hypertension are covered from children to adults with CKD, including transplant patients. It is clear that although there is a large database and store of knowledge, there are many fundamental questions that remain unanswered. In this issue of Advances in Chronic Kidney Disease, a broad spectrum of topics dealing with various aspects of hypertension and chronic kidney disease (CKD) are presented. Peter McCullough and colleagues highlight the fact that presence of CKD is a well-recognized and independent risk factor for cardiovascular disease (CVD) events, including stroke and myocardial infarction. A glomerular filtration rate of less than 60 mL/min or persistent microalbuminuria (<300 mg/g creatinine) are independent markers for increased cardiovascular risk. Estimation of glomerular filtration rate using serum creatinine and demographic factors, including age, gender, and race is now an accepted method of identifying those at risk for CVD events. For this reason, screening for early nephropathy among those with diabetes or hypertension is warranted. A rationale for multiple risk-factor intervention, including pharmacological as well as diet and life-style modifications, for reducing risk of both progression of CKD and development of CVD events is presented. The observations put forth by McCullough et al are further expanded by Yeo and colleagues in patients with stage 4 and 5 nephropathy. People with these stages of nephropathy are at much higher CVD risk than the general population or people with earlier stages of nephropathy. Moreover, people at these stages of nephropathy are not maximally treated to reduce blood pressure or CVD risk. These aspects of risk management and others are discussed. Blood pressure measurement in people on dialysis is challenging, with many unanswered questions. Niranjan Sankaranarayanan and colleagues have been studying this issue for some time and discuss in detail approaches to measurement of blood pressure in people on dialysis. They discuss not only different methodologies but also the role of 24-hour ambulatory measurements compared with routine measurements. They also deal with the troubling questions of when is the best time to measure blood pressure and under what circumstances. In a separate paper, Portman et al highlight the many challenges that face the management of hypertension in children with CKD. It is clear that hypertension in children results from diverse causes, particularly in early years, mostly from secondary forms. However, in older children, primary hypertension is much more common. This timely review indicates that accurate measurement of blood pressure in this vulnerable population includes routine methods, such as automated BP measures, as well as ambulatory blood pressure monitoring. Elevated blood pressure, as determined by either routine or ambulatory BP measurement, is associated with target-organ damage in children. The authors emphasize the need for better techniques to assist in early identification and intervention to reduce risk of subclinical end-organ involvement and for prevention of cardiovascular disease. Future investigations should focus on appropriate workup, criteria for use of potentially invasive and expensive diagnostic techniques, criteria for beginning antihypertensive therapy, and pharmacokinetic and pharmacodynamic properties of antihypertensive agents in children. On this background, questions remain as to the impact of early intervention on prevention of hypertensive complications later in life. Accordingly, the authors conclude that children with hypertension of any etiology should be primarily managed by those with extensive experience in pediatric hypertension and nephrology. In the paper by Ikizler, recent advances in our understanding of the relationships between nutrition and inflammation in the pathogenesis of CKD and its complications are discussed. New data on inflammatory markers in CKD, including C-reactive protein (CRP) and others in relation to nutritional status, morbidity, and mortality in CKD are reviewed. In addition, the role of oxidative stress in the pathogenesis and progression of CKD is discussed in some detail. There is clear evidence that uremic malnutrition and chronic inflammation are important comorbid conditions closely linked to CVD risk in people with ESRD. However, additional studies are needed to establish the pathophysiological link(s) between malnutrition, inflammation, and atherosclerosis in CKD patients. Both uremic malnutrition and chronic inflammation are also associated with increased oxidative stress, a condition proposed as a unifying concept of CVD in uremia. These and related data are discussed by the author. Further research in this area is likely to identify future treatment options to improve the high mortality and morbidity in ESRD patients. Weir discusses treatment and goal blood-pressure values in kidney transplant patients. In this area, as in dialysis, an accepted goal blood pressure, as well as ideal antihypertensive agent to confirm optimal protection, is unknown. Although many surgeons use calcium antagonists, many recent studies with biopsies of the transplanted kidneys suggest that block of the renin-angiotensin system confers greater long-term protection. Additionally, the author discusses the CVD risk associated with different levels of blood pressure in this patient group. In short, all aspects of hypertension are covered from children to adults with CKD, including transplant patients. It is clear that although there is a large database and store of knowledge, there are many fundamental questions that remain unanswered.