Hypertension and CKD

The recent increase in CKD nationwide is closely tied to the combined increase in prevalence of obesity, diabetes, and hypertension. Age also is an important contributor since people are living longer, with the average age of death for men and women increasing by a decade compared with the 1960s.

Robinson and colleagues noted that in 1999-2002, hypertension (both diagnosed and undiagnosed) was present in approximately 78% of older women and 64% of older men (Aging Trends. 2007;7:1-12). The odds ratio of CKD in the 1999-2006 NHANES data was 5.9 for those older than 60, 2.5 for those with diabetes, and 1.8 for those with known hypertension. The number of Americans older than age 65 is expected to increase from 30 million in 2000 to more than 45 million people in 2020, with greater than 65% of these individuals projected to have hypertension.

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Analysis of the NHANES data shows that the overall CKD prevalence among those older than 20 years of age was higher in 1999-2004 than in 1988-1994 (Am J Med. 2008;121:332-340). This was true for each of the five stages of CKD. The overall prevalence of CKD among men in 1988-1994 was 8.2% and in 1999-2004 11.1%. Among women, the prevalence was 12.1% and 15.0%, respectively. By ethnicity, rates increased from 10.2% to 11.7% in African-Americans, from 6.3% to 8.0% in Mexican Americans, and from 10.5% to 13.8% among non-Hispanic whites.

The relationship between hypertension and worsening of kidney function has been known for more than 50 years. In a seminal paper, Perry and colleagues showed that the longer a patient has high BP and the higher it is, the sooner he or she will need dialysis (Hypertension. 1995;25:587-594).

This observation is further supported by Klag and colleagues, who noted a consistent relationship between elevated systolic BP (SBP) or diastolic BP (DBP) and end-stage renal disease (ESRD) in the Multiple Risk Factor Intervention Trial (MRFIT) (N Engl J Med. 1996;334:13-18). The relative risk for ESRD progression was 20-fold higher in patients with what was previously known as stage 4 hypertension (SBP higher than 210 mm Hg or DBP higher than 120 mm Hg) than in patients with optimal BP levels.

When BP is elevated or when the renal autoregulatory mechanisms are blunted as a result of advanced CKD, diabetes, or BP consistently elevated above 160/100, a linear relationship between systemic BP and glomerular capillary pressure is seen. This increased pressure load on the kidney vasculature results in injury by multiple mechanisms. Prospective studies have clearly shown that lowering BP to levels around 140/90 reduces risk for CKD progression (Med Clin North Am. 2009;93:697-715).

Further lowering of BP to less than 130/80  appears to benefit only those with significant albuminuria, i.e., higher than 200 mg/day, and not all those with CKD. Physicians should be aware that evidence for renin angiotensin system blockers to protect against CKD progression is restricted to those with advanced proteinuric nephropathy. Patients involved in trials with positive results for such end points as doubling of creatinine and progression to ESRD had glomerular filtration rates below 50 mL/min and proteinuria generally greater than 500 mg/day.

A rise in serum creatinine of 30%-35% during the treatment of such patients translates into long-term improvement in CKD outcomes and not worsening of kidney function (Arch Intern Med. 2000;160:685-693 and J Hum Hypertens. 2005;19:389-392). This was a common occurrence in trials in which all outcomes related to CKD, and therapy was continued. Hence, treatment with such agents should not be stopped if a rise in creatinine of this magnitude occurs.

What the future holds

The demographic and risk factor analyses presented predict a grim future unless something is done at a public-health level to manage the risk factors for hypertension. If racial disparities, access to health care, obesity, and the incidence of diabetes mellitus continue to rise at current epidemic rates, the economic impact of hypertension-related conditions will be staggering. The health-care budget will suffer a huge blow and will not be able to support the already overburdened primary-care system, with its direct and indirect cost of hypertension alone currently estimated at $73.4 billion for 2009.

One approach to curtailing the problem of hypertension has been put forth in a call to action document. This document summarizes the report of a group of international experts whose goal was to reduce cardiorenal disease by improving adherence and identification of hypertension. In summary, the group concluded that tackling the global challenge of hypertension would require partnerships among multiple constituencies, including patients, health-care professionals, industry, media, health-care educators, health planners, and governments.

Additionally, health-care professionals will need to act locally and with renewed impetus to improve the rates of patients meeting BP goals. This is already happening through the efforts of the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP).

The KEEP Working Group identified five core actions that should be rigorously implemented by practitioners and targeted by health systems throughout the world. These five core initiatives include (1) detection and prevention of high BP; (2) assessment of total cardiovascular risk; (3) formation of an active partnership with the patient; (4) treatment of hypertension to goal, and (5) creation of a supportive environment. Physicians should pursue these actions with vigor and in accordance with current clinical guidelines, adapting the details of implementation to the economic and cultural setting (J Hum Hypertens. 2008;22:63-70).

Dr. Hopkins is a fellow in the Hypertensive Diseases Unit, Department of Medicine at the University of Chicago, Pritzker School of Medicine, where Dr. Bakris serves as the Director