Clinical Review

The Management of Hypertension in Elderly Patients with Chronic Kidney Disease


 

References

From the Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM.

Abstract

  • Objective: To review the available literature regarding hypertension and chronic kidney disease (CKD) in the elderly and provide a framework for clinical management of hypertension in this subset of the elderly population.
  • Methods: Review of the available literature.
  • Results: Though several large, well-designed randomized trials exist examining the treatment of isolated hypertension in the elderly, these trials have uniformly excluded patients with CKD, thus reducing the generalizability of these results to this subgroup. CKD in the elderly is poorly studied overall, and whether CKD in the elderly is an expected product of senescence or a pathology from modifiable risk factors is debatable. Concern exists regarding the increased potential of acute kidney injury events and a more rapid progression of CKD with more aggressive hypertension lowering in elderly patients.
  • Conclusion: Though data is limited regarding hypertension treatment in the subset of elderly patients with CKD, given the consistent benefits in cardiovascular reduction with hypertension treatment in the general elderly population, it is likewise recommended that elderly patients with hypertension and CKD receive antihypertensive therapy, though with more careful monitoring for adverse renal effects. We provide a practical approach to management for this clinical scenario.

Chronic kidney disease (CKD) is an increasingly recognized finding in elderly patients, with approximately half of all patients over the age of 70 meeting the most common currently accepted definition of CKD stage III, an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 [1]. Whether this finding is a result of normal physiologic aging or whether it represents a true disease process in elderly patients has been a matter of considerable debate [2–4]. Nonetheless, the decline in eGFR in elderly patients has important implications regarding drug dosing and the potential risk of acute kidney injury (AKI) in this population [5–9]. Additionally, elderly patients with reduced GFR may have an increased risk of cardiovascular events and progression to end-stage kidney disease (ESKD), though extensive studies are lacking in this population [10–13].

In contrast, isolated hypertension and its treatment in the elderly population has now been extensively evaluated in several well-designed, prospective randomized studies, with generally favorable results arguing for the treatment of hypertension in elderly individuals [14–17]. Unfortunately, however, these studies have uniformly excluded patients with CKD in their study designs. Thus, the impact of aggressive hypertension management in elderly patients with CKD is unknown. As a considerable proportion of CKD in this population has been felt secondary to vascular disease and poor overall vascular health, many have questioned whether aggressive blood pressure reduction, particularly in patients with wide pulse pressure as an indicator of vascular disease, may result in decreased overall renal perfusion and greater risk for AKI, and thus potentially accelerate renal decline in this population [18–22].

In this paper, we review the epidemiology and physiology of renal disease in the elderly, provide an analysis of the available data regarding management of hypertension in the elderly, and suggest an approach to management of hypertension in this specific patient population. Though a multitude of age cutoffs defining elderly have been proposed, for the purposes of this paper we define elderly as age greater than 65 years unless otherwise specified.

Definition of CKD

The currently accepted definition of CKD represents any composite of pathology resulting in impaired kidney function, defined as a drop of GFR < 60 mL/min/1.73 m2 for 3 months or longer, or a higher GFR but with evidence of structural or functional abnormalities, such as proteinuria [23]. However, there are key aspects and important limitations to the above diagnostic criteria to be considered in the elderly patient population. Importantly, the most commonly used GFR estimation equations use serum creatinine as the marker for impaired renal function. As serum creatinine levels are also determined by overall muscle mass, significant error in estimating GFR can occur using these equations in elderly patients, who may have widely varying degrees of musculature and thus creatinine production. Additionally, these equations were often derived using all CKD or mostly CKD patients, which may result in healthy individuals having a higher GFR at the same serum creatinine levels than CKD patients, thus incorrectly classifying many patients with normal kidney function as having CKD [24].

Serum cystatin C has been proposed as an alternative surrogate marker for impaired kidney function, particularly in the elderly, as it is not affected by muscle mass. However, cystatin C levels are affected by obesity, inflammation, and atherosclerosis, and thus equations using this marker to determine GFR also face some limitations in the elderly population [25]. Evidence comparing various GFR estimating equations in the elderly suggest that formulas that use a combination of serum creatinine and cystatin C do best at predicting GFR when compared to gold standard techniques, such as iohexol clearance, though it is important to note that yet the ideal GFR estimating equation for elderly patients has not been determined [26–28].

It has been suggested that given these limitations and potential to underestimate GFR in the elderly population, a lower GFR reference range of 45 mL/min/1.73 m2 be used in the absence of other signs of kidney damage given the multiple unique characteristics of the aging kidneys, as we will explore in this review [29]. In general, we are in agreement with this suggestion that all elderly patients with a creatinine based estimated GFR of < 45 mL/min/1.73 m2 can safely be assumed to have CKD, and it is our opinion that elderly patients with a GFR > 45 mL/min/1.73 m2 but less < 60 mL/min/1.73 m2, without other signs of structural of functional renal disease such as proteinuria, have additional evaluation for the presence of impaired renal function, including but not limited to the addition of cystatin C to estimate GFR.

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