Epidemiology of CKD in the Elderly
According to the Centers for Disease Control and Prevention (CDC), the number of elderly patients in the United States is expected to double in the next 25 years to 72 million patients, representing approximately 20% of the adult population by 2030 [30]. Analysis of the National Health and Nutrition Examination Surveys (NHANES) from 1999–2004 revealed an overall prevalence of CKD in the US population of 13.1%. However, when sub-grouped into patients greater than or equal to 70 years of age, the prevalence of CKD in this population increased to a staggering 47.5% [31]. Likewise, analysis of other elderly populations from Canada, China, Italy, and Spain indicated a roughly 3- to 7-fold increase in CKD prevalence in those elderly populations compared to younger patients [3]. Additionally, according to the United States Renal Data System there is evidence of a progressive rise in the number of end-stage renal disease (ESRD) patients enrolled in Medicare-funded programs over the past decades [32]. In extrapolating these estimates, it is conceivable to predict that approximately 30 million elderly patients may have CKD in the United States by year 2030, with enormous implications to treatment recommendations and healthcare associated costs.
The Aging Kidney and Expected Rate of Nephron Loss
A progressive, age-related decline in GFR has been demonstrated in many studies. In an earlier analysis of the Baltimore Longitudinal Study of Aging by Lindeman et al, a decline in measured creatinine clearance of 0.75 mL/min/year was demonstrated. It is important to note that in this analysis, patients with suspected pre-existing renal or urologic disease and those on diuretics or other antihypertensives were excluded from analysis, and a normal Gaussian distribution of creatinine clearance slopes versus time was demonstrated, suggesting the GFR loss was a process of normal aging [4].
In support of the theory of a physiologic age-related decline in renal function, a study by Rule et al analyzed potential kidney transplant donors for age-related decline in renal function and determined an approximately 6.3 mL/min/1.73 m2 decline in GFR for each decade. In this investigation, core needle biopsies were obtained at the time of donation and transplantation. The investigators found a progressive increase in the histologic prevalence of nephrosclerosis with each age group analyzed, increasing from 2.7% at ages 18 to 29 to 16% for ages 30 to 39, 28% for ages 40 to 49, 44% for ages 50 to 59, 58% for ages 60 to 69, and finally 73% in donors older than age 70. It is important to note that this study only examined live kidney donors, a group heavily screened and selected on the basis of optimal health, thus strongly arguing for progressive renal decline as a consequence of “normal” aging. Furthermore, though controlled hypertensive patients (treated with 2 or less medications) were allowed to be donors in this study, exclusion of this group had only a minimal impact on the findings of the study [33].
However, whether this age-related decline is purely a result of normal senescence or is a consequence of modifiable risk factors that could alter this outcome remains debatable. Additionally, vascular disease is clearly implicated in more accelerated renal decline. This concept was well demonstrated in an analysis of the longitudinal Age, Gene/Environment Susceptibility – Reykjavik Study, which showed that although age was associated with both reduced GFR and albuminuria, reduced GFR and albuminuria in elderly patients (mean age 80.8 yr) was strongly associated with midlife systolic and diastolic blood pressure, thus suggesting that potentially modifiable vascular pathology may play a much stronger role in CKD in the elderly than aging alone [34].
Finally, it has been hypothesized that reduced nephron mass at birth may contribute to CKD in the elderly [29]. Reduced nephron mass appears to be associated with low birth weight and prematurity, and this has been associated with an increased risk for ESRD later in life [35,36].
Hypertension in the Elderly
Pathophysiology
Age-associated hypertension is felt to arise from several mechanisms and hemodynamic changes. Systolic blood pressure has been noted to progressively rise with age, whereas diastolic blood pressure rises to the 5th or 6th decade, after which it appears to slowly decline. This pattern is felt likely secondary to increasing large vessel stiffness from collagen deposition and calcification with aging, and fracturing and degradation of elastin fibers. As large vessels become less distensible, pulse pressure and pulse wave velocity increases with this drop in diastolic BP, with less forward flow seen in diastole, leading to decreased organ perfusion. Additionally and alternatively, concentric left ventricular hypertrophy develops with aging, leading to reduced cardiac output from decreased stroke volume, which may also contribute to reduced organ perfusion [37,38]. These findings have led many to speculate that hypertension in the elderly may actually serve as a protective mechanism to maintain organ perfusion, and have led to great concern regarding excessive lowering of diastolic blood pressure and increasing of pulse pressure in this population with antihypertensive therapy. This theory was initially corroborated with a sub-analysis of the Systolic Hypertension in the Elderly Program (SHEP) where an increase in pulse pressure by 10 mm Hg was accompanied by increased risk of stroke and congestive heart failure in the treatment arm [39]. Nonetheless, the bulk of evidence continues to support a lower overall risk of cardiovascular events with treatment of hypertension in elderly patients, and general expert consensus recommends treatment with gradual reduction to normal levels of systolic blood pressure accompanied by careful monitoring for adverse effects [40,41].