The Message for World Kidney Day 2009: Hypertension and Kidney Disease: A Marriage That Should Be Prevented

Abstract

The prevalence of chronic kidney disease (CKD) continues to increase worldwide as does end stage renal disease. The most common, but not only, causes of CKD are hypertension and diabetes. CKD is associated with a significant increase in cardiovascular (CV) risk as most patients with CKD die of a CV cause. Moreover, CV risk increases proportionally as estimated glomerular filtration rate falls below 60 mL/min. CV causes of death in CKD are more prevalent than those from cancer; as a result, the identification and reduction of CKD is a public health priority. High blood pressure is a key pathogenic factor that contributes to the deterioration of kidney function. The presence of kidney disease is a common and underappreciated preexisting medical cause of resistant hypertension. Therefore, treatment of hypertension has become the most important intervention in the management of all forms of CKD. For this reason, World Kidney Day on March 12, 2009 will emphasize the role of hypertension.

The kidney is both a cause and a victim of hypertension. High blood pressure (BP) is a key pathogenic factor that contributes to deterioration of kidney function. Presence of kidney disease is a common and underappreciated preexisting medical cause of resistant hypertension. ¹ Therefore, treatment of hypertension has become the most important intervention in the management of all forms of chronic kidney disease (CKD). For this reason, the World Kidney Day on March 12, 2009, emphasized the role of hypertension in CKD.

How Does One Recognize the Presence of CKD?

In contrast to a decade ago, today most laboratories around the world report estimated glomerular filtration rate (eGFR) instead of or in addition to serum creatinine. This now provides the physician with information about kidney function that is, in general, more precise. As a result, a greater percentage of patients with diabetes or hypertension and their physicians have a better measure of kidney function. Assessment of eGFR as an index of kidney function should be complemented by examining urine for protein or albumin (preferred).

In spite of these laboratory updates, recent data demonstrate that a given patient’s knowledge that he or she has CKD is very low. In a recent analysis of almost half a million people in Taiwan who took part in a standard medical screening program, 12% had CKD, defined as an eGFR <60 mL/min. ² It was noteworthy that <4% of those with CKD were aware of their condition. These data may not, however, be applicable to other populations. People with CKD are several times more likely to die from cardiovascular (CV) causes than those without CKD. Hypertension is a major risk factor in these patients. ³ The combination of CKD and hypertension, therefore, is an important public health issue. Because of the costly treatments necessary for end‐stage renal disease (ESRD), end‐stage CKD has become a substantial burden to health budgets.

What is the Worldwide Frequency of CKD?

The frequency of CKD continues to increase worldwide, as does the prevalence of ESRD. ⁴ , ⁵ The most common, but not only, causes of CKD are hypertension and diabetes. The presence of CKD is associated with a large increase in CV risk. Moreover, CV risk increases proportionally as eGFR falls below 60 mL/min. Lastly, death from CV causes is higher in patients with CKD and much higher than cancer in patients with CKD. As a result, the identification and reduction of CKD has become a public health priority. ⁶

The reported prevalence of CKD stages 1 through 4 (eGFR >15 to <120 mL/min) in the most recent National Health and Nutrition Examination Survey (NHANES) between 1999 and 2006 was 26 million out of a population base of approximately 200 million. This represented US residents aged 20 years and older. Of these, 65.3% had CKD stage 3 or 4. Those with diabetes and hypertension had a greater prevalence of CKD (37% and 26%, respectively) compared with those without these conditions (11% and 8%, respectively). ⁷ In a more recent yet unpublished report from the CKD surveillance group, the prevalence or number of CKD stages 1 through 4 in the general population increased 30% from 1994 to 2006.

The most recent report of the US Renal Data System estimates that nearly half a million patients in the United States were treated for ESRD in the year 2004, ⁸ and by 2010 this figure is expected to increase by approximately 40%. Patients destined to progress to ESRD (ie, the elderly) are a growing segment of the population. In addition, men and African Americans with preexisting hypertension and CKD are also at much higher risk for ESRD. ⁹ This observation has also been confirmed throughout the developed world, including Europe, Asia, Australia, and regions of India and Africa. ⁴ , ⁵

The Role of Hypertension

Hypertension is a global problem that is projected to get worse. It is the major risk factor for the development and progression of CKD in nondiabetic and diabetic individuals.

The world population is getting older and aging is the most common risk factor for the development of hypertension and diabetes as well as CKD. Nearly one billion people worldwide have high BP (defined as >140/90 mm Hg), and that number is expected to increase to 1.56 billion people by 2025. ¹⁰ The predicted prevalence of hypertension will increase by 24% in developed countries and by 80% in developing regions such as Africa and Latin America. One report noted that 333 million adults in economically developed regions such as North America and Europe had an elevated BP in 2000; an additional 639 million people in developing countries have this condition.

In 1999–2006, the prevalence of hypertension in US adults was 43.4% when defined as >140/90 mm Hg and similar figures have been reported from many Western countries. ⁹ The rates of hypertension were highest in participants who were 60 years or older, ie, 68% to 80% compared with 25% in those between 20 and 39 years, in non‐Hispanic blacks (53%) vs Caucasians (43%) vs Mexican Americans (34%). Furthermore, hypertension was more common in individuals with a higher body mass index (BMI) (60% for BMI ≥35 vs 32% for BMI of 23). Slightly more than half of adults with hypertension were aware of their disease in 1999–2004; fewer than half were treated for their hypertension with medications; and <two thirds were controlled to <140/90 mm Hg with medication. ⁹ This trend in poor BP control is observed worldwide.

The hypertension control rate, defined as a BP <130/80 mm Hg, is substantially less in patients with CKD, particularly those with diabetes and CKD. ¹ , ⁹ This is illustrated by the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP), a US‐based health‐screening program for individuals at high risk for kidney disease. ⁹ The prevalence (86.2%), awareness (80.2%), and treatment (70.0%) of hypertension in the screened cohort was high; however, BP control rates were low (13.2%). The proportion of hypertensive patients increased with advancing stages of CKD.

Which BP Component is Most Relevant for Renal and CV Risk: Systolic or Diastolic?

There is now consensus, based on the totality of the data, that systolic rather than diastolic BP poses the greater risk for CV events and kidney disease progression. Against this background, it is relevant that in the KEEP study, elevated systolic BP accounted for the majority of patients with inadequate control. Male sex, non‐Hispanic black race, and BMI ≥30 kg/m² were inversely related to BP control.

What is the BP Target for CKD Patients?

According to the different guidelines published by the major kidney societies, systolic BP should be lowered to values <130 mm Hg. One has to be aware, however, that as a predictor of adverse CKD or CV events, office BP may be inferior compared with ambulatory BP measurement. ¹¹ This issue is particularly relevant in CKD because of the tendency for nighttime BP to be elevated (little or no nocturnal dip in BP) and the fact that central (aortic) BP tends to be higher than peripheral (brachial) BP. ¹¹ , ¹² In patients with diabetes, guidelines all recommend that lower BP targets may provide further CV benefit, but prospective trials assessing BP values to <130/80 mm Hg have thus far failed to confirm this epidemiologic observation.

The Role of Diabetic Nephropathy

As indicated above, diabetes and hypertension are the most common causes of CKD. There are currently more than 240 million people with diabetes worldwide. This figure is projected to rise to 380 million by 2025, largely due to population growth, aging, urbanization, unhealthy eating habits, increased body fat, and a sedentary lifestyle. Another factor may be that fewer people are dying from strokes, heart failure, and coronary disease at ages between 50 and 70 years and therefore living to an age when CKD becomes detectable. By 2025, the number of people with diabetes is expected to more than double in Southeast Asia, the Eastern Mediterranean and Middle East, and Africa. It is projected to rise by nearly 20% in Europe, 50% in North America, 85% in South and Central America, and 75% in the Western Pacific region. The top 5 countries with the highest prevalence of diabetes in order include India, China, the United States, Russia, and Japan. Worldwide, more than 50% of people with diabetes are unaware of their condition and are not treated.

The same behaviors that increase obesity are shared with those predisposed to diabetes, ie, family history, presence of hypertension, aging, excess body weight, lack of exercise, and unhealthy dietary habits. It is important to identify these risks early to reduce the development of diabetes and CKD, since CKD greatly amplifies the risk of CV events in the diabetic patient.

The Remaining Challenge

Underdiagnosis and undertreatment of CKD is a worldwide problem. Not only is CKD awareness low worldwide, but the relative lack of CKD risk factor awareness by physicians (ie, hypertension and diabetes) is even more disturbing. Moreover, even awareness of these risk factors does not ensure adequate treatment. This could relate either to the behavior of the patient, the provider, or both. Thus, the problem of CKD remains a challenge as exemplified by recent data showing that between 1999 and 2006, <5% of people with an eGFR <60 mL/min/1.73 m² and proteinuria were aware of having CKD. Of those with CKD stage 3, awareness was only 7.5%; for stage 4, awareness was <50%. Awareness rates among those with CKD stages 3 or 4 were higher if comorbid diagnoses of diabetes and hypertension were present, but even then, they were quite low (20% and 12%, respectively).

One barrier to overcome in order to ensure greater awareness is a more focused education of physicians, since they treat these patients. In one survey, more than one‐third of primary care physicians in the United States were not aware that family history was a risk factor for CKD, while almost a quarter did not perceive African American ethnicity as a CKD risk factor. In contrast, nearly all perceived diabetes (95%) and hypertension (97%) as risk factors for CKD. Even more problematic was the fact that while diabetes and hypertension were acknowledged as CKD risk factors, the achieved control rates (defined as reaching guideline goals) sadly remains well below 50% among those treated.

What Can be Done About this Problem?

There have been many consensus panels over the past decade to approach ways to achieve better BP control and educate physicians to the stages of CKD. ¹³ , ¹⁴ The approach to improve outcomes is to focus on public awareness and screening programs as well as programs to educate both patients and physicians. Data from the KEEP screening program in the United States have also noted that BP values are most likely to be at goal once a patient is aware that they have kidney disease. ¹⁵ Data from Bolivia highlight the observation that once kidney disease is diagnosed, more appropriate interventions to reduce CKD risk factors such as hypertension are instituted. ¹³

Programs to address these issues have started around the world, including KEEP‐type programs. As a major focus of World Kidney Day this year, the issue is hypertension in CKD (http://www.worldkidneyday.org).

Because of the aging world population and consequent increasing prevalence of hypertension and diabetes, CKD rates will continue to increase. This has and will continue to place an undue economic burden on societies given the costs for an ESRD program. In 2005, the United States spent $32 billion on such programs. These facts mandate that measures be implemented to ensure timely detection and prevention of CKD progression. The key to ensure successful prevention of CKD is screening for hypertension, improved testing, and diagnosis of predisposing comorbidities such as diabetes and aggressive treatment to guideline goals.

The International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF) have an ambitious long‐term worldwide goal: that every individual, particularly the patient with diabetes, knows his or her BP values. In addition, they should be aware that prompt treatment is necessary once BP values are no longer in the normal range. Finally, our societies strongly encourage public health authorities to support efforts to raise public awareness about CKD and promote moves to reduce the risk of developing hypertension. Such governmental public health initiatives are exemplified by countries like the United Kingdom, Finland, and Japan that have mandated that labels on food list sodium content. This has also been done in the United States. These initiatives have proven highly successful based on reduction in CV mortality and morbidity.