Identification and Management of Chronic Kidney Disease in Older Adults

Introduction

Chronic kidney disease (CKD) affects approximately 16.8% of the U.S. population age 20 years or older, or an estimated 50 million people, and recent estimates from the United States Renal Data System suggest that the prevalence of CKD is increasing.¹ CKD is particularly prevalent among elderly patients, with as much as 30% of adults over age 70 and 50% of adults age 80 and older having abnormal renal function.² The high prevalence is complicated by the fact that the world’s elderly population is increasing due to the increased birth rate after World War II and the 20-year increase in the average lifespan that has occurred over the last half of the twentieth century.³ As the U.S. population ages, chronic diseases will become ever more prominent causes of morbidity and mortality. Although the elderly make up a rapidly growing segment of the CKD population, defining and managing CKD specifically in older adults (≥ 65 years) is poorly defined.

CKD may lead to end-stage disease (ESRD) and is also associated with increased risk of mortality, premature death, cardiovascular disease, heart failure, and increased healthcare expenditures.^1,4,5 Progression to ESRD (requiring dialysis or transplantation) is an ongoing risk for patients with CKD; ESRD is associated with significant morbidity and high medical costs.¹ The annual incidence of ESRD represents a small fraction of the total number of patients with CKD.⁶ The disparity between the staggering number of patients with CKD and the relatively smaller number of patients who progress to ESRD stems in part from the high mortality rate of patients with CKD. The majority of patients with CKD die before progressing to ESRD; older adults with CKD are even more likely than their younger counterparts to die than to progress to ESRD.⁷

Given the high prevalence and increasing incidence of CKD, the identification and management of patients with CKD need to be optimized to minimize patient risk and reduce healthcare costs. Recent advances in the diagnosis of CKD using estimated glomerular filtration rate (eGFR), an estimated percentage of renal function, may have elucidated the increase in incidence, especially among older patients.⁸ Identifying CKD early is necessary to limit disease progression, sequelae, and cost. As mentioned, older adults with CKD are less likely to experience progression to ESRD; the degree to which older adults experience comorbidities related to CKD and at what level of kidney dysfunction are unknown.^6,7 As a result, an age-specific and tailored approach to CKD care for older patients may be of benefit.

Pathophysiology of the Aging Kidney

The kidneys, and kidney function, can change with age. Between young adulthood (approximately age 40) and age 90, kidney weight and mass decline by as much as 80 grams, a decrease by approximately half the weight of an average adult kidney.⁹ The size of the body itself also changes somewhat with age, and calculations that account for changes in body surface area show that the loss of kidney size appears to be commensurate with the loss of body surface area. Biopsy examinations of older kidneys exhibit more glomerulosclerosis (scarring of the glomerulus, which is the functional unit of the kidney) and increased tubulointerstitial fibrosis (associated with chronicity of renal dysfunction) as compared with younger kidneys. Renal blood flow declines with age by as much as 10% per decade, but this seems to specifically affect cortical tissue, where there is also often a loss of cortical vasculature.⁹ Despite these known physical changes in the kidneys, the ways in which kidney function may change with age is less clear.

The Baltimore Longitudinal Study of Aging examined changes in measured creatinine clearance (a method to evaluate renal function using 24-hour urine studies) with age.¹⁰ Researchers noted a mean decline in creatinine clearance of 0.75 mL/min/1.73 m² per year. Within their data, one-third of subjects showed a slow decline in creatinine clearance, one-third showed a more rapid decline, and one-third of subjects examined did not show a decline in renal function with age.¹⁰ The degree to which renal function decline is expected or “normal” with age remains unknown.

Identifying Chronic Kidney Disease

To help more accurately identify CKD, researchers developed the Modification of Diet in Renal Disease (MDRD) eGFR equation, using cohort data from the MDRD study.⁸ Prior to the MDRD eGFR equation, several mechanisms for estimating renal function were available. Direct measurement of GFR via inulin or iothalamate is both technically difficult and expensive, making these methods impractical for everyday clinical use. Measured serum creatinine alone overestimates renal function, both because of creatinine secretion and because the true “normal” value of creatinine varies both with muscle mass and age.⁸ Patients with smaller muscle mass have lower serum creatinine levels than those with greater muscle mass, and may be misclassified as “normal.” Women and the elderly are two populations in whom this difference may be noted, as muscle mass in these persons may be lower than in men and younger individuals, respectively. The eGFR equation takes into account not just creatinine but also age, gender, and race (which can also affect creatinine generation), thereby providing a more accurate reflection of true renal function and improved recognition of CKD.⁸ Use of eGFR equations is intended to allow physicians to better recognize renal dysfunction in patients with normal serum creatinine levels but functionally abnormal filtration rates. Use of eGFR in place of creatinine alone may result in earlier recognition of CKD, especially in those populations.

In an effort to better identify patients with CKD, the National Kidney Foundation developed the Kidney Disease Outcomes Quality Initiative (KDOQI) “Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification.”¹¹ These guidelines recommend the use of the MDRD eGFR equation to avoid the problems associated with direct GFR measurement and the inaccuracies of serum creatinine and creatinine clearance tests. In these guidelines, the KDOQI defined the stages of CKD as follows: stage 1 = GFR ≥ 90 mL/min/1.73 m²; stage 2 = GFR 60 to 89 mL/min/1.73 m²; stage 3 = GFR 30 to 59 mL/min/1.73 m²; stage 4 = GFR 15 to 29 mL/min/1.73 m²; and stage 5 (kidney failure) = GFR < 15 mL/min/1.73 m² or ongoing dialysis or transplantation.¹¹

Despite the KDOQI guidelines endorsing the use of eGFR, nephrologists are beginning to debate the utility of eGFR as a screening tool for the identification of CKD. Although serum creatinine may overestimate decreased renal function, eGFR may underestimate normal renal function, especially among the elderly.^12,13 Thus, some argue that using eGFR as a screening tool for the identification of CKD may result in a significant number of false-positive tests.¹⁴ Using a screening test with a high false-positive rate has the most value when a secondary test exists that can clarify the presence or absence of true disease. No such test is clinically available for CKD. In addition to resulting in false-positive tests, eGFR identifies many cases of CKD in patients who are unlikely to progress to ESRD, particularly among the elderly.⁶ Thus, using eGFR as a screening test may result in unnecessary referrals and increased expense among patients who have minimal risk of CKD progression.¹³

CKD in the Elderly: A Disease or a Condition?

The previous discussion highlighted the uncertainty of whether the current definition of CKD is appropriate for older adults, which is a significant problem because the elderly represent a large portion of newly recognized patients with CKD.^1,2 Because a decline in GFR is prevalent among aging populations, it is difficult to interpret its clinical significance.^10,15 In addition, older adults appear to manifest their CKD differently as compared with their younger counterparts. A prospective cohort study published in 2006 illustrated a high prevalence of CKD in the community-dwelling elderly, but also showed a slow rate of progression to ESRD.¹⁶ A retrospective cohort study published in 2007 found that patients age 65 to 84 years had to have an eGFR of less than 15 mL/min/1.73 m² (stage 5 CKD) to have a greater risk of ESRD than of death by any cause.⁷ Whether older adults carry the same risk for other CKD sequelae (such as anemia and bone disease) as younger patients remains unclear.

It is this uncertainty that fosters questions regarding CKD definitions and management in older patients. The concern for the need to modify definitions for CKD in the elderly is based on the lack of disease progression in the overwhelming majority of elderly patients. Conversely, in the absence of the risk of progression to ESRD, older patients with CKD may still be at risk for increased mortality, cardiovascular outcomes, and additional comorbidities, such as CKD-mineral bone disorder and CKD-related anemia. The rate of comorbidities related to CKD occurring at different levels of eGFR in the elderly remains largely unknown. Additionally, as illustrated by the results of the Baltimore Longitudinal Study of Aging, it is clear that not all individuals experience decreasing creatinine clearance with advancing age.¹⁰ As such, asserting that a lower GFR is “normal” in all elderly individuals is problematic. Without definitive studies to demonstrate both decreased risk of progression to ESRD and decreased occurrence of CKD-related comorbidities, CKD in the elderly is still considered a disease.

Diabetes in the Older Adults: A Model for Age-specific Disease Management

The field of diabetes serves as an excellent example of how age-specific modifications to guidelines can optimize the care and the quality of life for elderly persons with a specific disease or condition. For instance, in 2003, the American Geriatrics Society published its “Guidelines for Improving the Care of the Older Person with Diabetes Mellitus,” which suggested that less stringent blood glucose control is reasonable in those elderly patients who have a limited life expectancy.¹⁷ In some cases, more rigorous control can lead to increases in adverse outcomes, such as hypoglycemia. These guidelines placed special emphasis on managing comorbidities that are likely to impact the elderly patient’s quality of life, such as cardiovascular disease.¹⁷ A decision analysis by Huang et al¹⁸ examined this issue in an attempt to identify patients in whom intensive blood glucose control would be of less value. The authors elucidated that, in patients age 60 to 80 years, the higher the level of comorbid illness and the longer the duration of diabetes, the less benefit that would be derived from intensive blood glucose control in terms of quality-adjusted patient days.

CKD in the Older Adults: Management of Hypertension

Using the case of care for elderly patients with diabetes as a model, the modification of CKD guidelines specifically for older adults with CKD offers the same opportunity to optimize both care and quality of life. A major comorbidity in patients with CKD that affects the progression of disease as well as cardiovascular outcomes and mortality is hypertension. Tailoring more age-specific hypertension management guidelines for older adults with CKD could potentially have a significant impact on their disease. The area of diabetes differs from that of CKD in that more trial data in elderly patients with diabetes are available to impact guideline development. In the area of CKD, data that are specific to older patients with CKD are sparse. Until more trial data become available, we must consider what is known about CKD in general and about hypertension in older adults without CKD to help guide our care decisions.

Hypertension management in patients with CKD is relatively straightforward; the KDOQI guidelines recommend a blood pressure of lower than 130/80 mm Hg for all patients with CKD, regardless of age.¹⁹ Data for this hypertension guideline were developed in cohorts of patients age 70 and younger.^20,21 Hypertension management in older adults without CKD is more complex, and research in this area has changed over time. Early investigation of hypertension management among elderly patients without CKD found that lower blood pressures were associated with a higher rate of mortality.²² Later, research suggested that hypotension may be a marker for illness severity.²³ Since that time, cohort studies have illustrated that, when comorbidities are controlled for within the study design, low blood pressure does not correlate to higher mortality rates in older adults, unless the patient’s blood pressure is less than 140/90 mm Hg.^23,24

So, what blood pressure goals should clinicians target for older adults? The randomized, double-blind trial from the Systolic Hypertension in the Elderly Program (SHEP) research group helped to begin to address this question.²⁵ Researchers found that patients over age 60 who received a diuretic to lower their systolic blood pressure (achieved systolic blood pressure of 143 mm Hg on average) had a lower risk of stroke and cardiovascular outcomes as compared with those who were treated with placebo (who had an average systolic blood pressure of 155 mm Hg).²⁵ The most recent data in this subject area come from the Hypertension in the Very Elderly Trial (HYVET).²⁶ This randomized, controlled trial examined 3845 patients, 80 years and older, who were randomized to a diuretic with or without an angiotensin-converting enzyme inhibitor versus placebo; these patients were followed for 2 years. HYVET confirmed a decreased risk of stroke and overall mortality in those patients who were treated for their hypertension versus control patients who were untreated. Of note, the average systolic blood pressure in the treated group at 2 years was approximately 140 to 150 mm Hg, versus 160 to 170 mm Hg in the control group.²⁶

As CKD was an exclusion criterion in many of these trials, it is difficult to extrapolate these data to older adults with CKD. Although data among these older adults without CKD suggest a benefit of some hypertension management, they also showed it to be detrimental in individuals with blood pressures of lower than 140/90 mm Hg—a value above that recommended by CKD guidelines for blood pressure management.^19,24 

Although there are clear guidelines from several organizations regarding goals for blood pressure in patients with CKD, there are no age-specific guidelines for elderly patients with CKD (Table).^19,24-30 Both the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure²⁷ and the 2007 European Society of Hypertension-European Society of Cardiology Guidelines for the Management of Arterial Hypertension²⁹ recommended avoiding severe diastolic hypotension in older adults (avoid diastolic blood pressure < 55-60 mm Hg), but these guidelines are not specifically for older adults with CKD. The KDOQI guidelines¹⁹ and guidelines from the National Collaborating Centre or Chronic Conditions (NCC-CC)/National Institute for Health and Clinical Excellence (NICE)²⁸ do not make specific recommendations or modifications to blood pressure goals for older patients with CKD. Based on the available data, applying the current age-neutral CKD guidelines for blood pressure control (< 130/80 mm Hg) in the elderly with special care during drug titration to avoid diastolic hypotension is the most appropriate management. More outcome data regarding mortality, progression to ESRD, and hospitalization in older patients with CKD are needed to further modify blood pressure guidelines for this unique age group.

Conclusion

The number of elderly patients with CKD is already high and is expected to grow over the next decade. A diagnosis of CKD increases the risk of progression to ESRD (requiring dialysis or transplantation), mortality, cardiovascular disease, mineral bone disorder, and anemia. There is an ongoing debate regarding the definition of CKD in the older adults, based on some data that suggest that a decline in GFR may be part of the normal aging process and because these patients are less likely to progress to ESRD; however, there are no data to suggest that older patients who meet the current definition criteria for CKD are less likely to experience the associated CKD comorbidities, including increased risk of cardiovascular disease and mortality. On the basis of the data that are currently available, the standard of care remains to apply the guidelines identifying CKD to patients of all age groups, including the elderly.

Other specialties have begun to examine guidelines for disease management in the specific context of elderly patients. Diabetes serves as an excellent example of this, and guidelines for glycemic control among older adults have been adjusted to help optimize both care and quality of life among older persons with diabetes. A similar tactic for CKD guidelines might similarly benefit elderly patients with CKD, but the paucity of trial data makes the process of guideline adjustment challenging. Hypertension management in older adults with CKD presents a particular dilemma, as the blood pressure goal for patients with CKD is lower than the recommended blood pressure goal for older patients without CKD. Available data dictate that careful titration of blood pressure toward CKD guideline goals, with specific avoidance of hypotension or diastolic blood pressures of less than 55 to 60 mm Hg is the best way to achieve standard of care, with special consideration appropriate to patients in this age group. Trial data in the future may help better define blood pressure goals and many facets of CKD care specifically for older adults.

The authors report no relevant financial relationships. Dr. Weiss is Instructor in Nephrology, Oregon Health & Science University, and Post Doctoral Fellow in Research, Kaiser Permanente Center for Health Research, Portland, OR; Ms. Petrik is Research Associate, Kaiser Permanente Center for Health Research, Portland, OR; and Dr. Thorp is Chief of Nephrology, Kaiser Permanente Northwest, and Clinical Assistant Professor, Oregon Health & Science University, Portland, OR.

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