The Management of Older Adults With a Low eGFR: Moving Toward an Individualized Approach

In the general population, approximately 38% of adults 70 years or older have an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2; most have moderate reductions in eGFR in the 30- to 59-mL/min/1.73 m2 range.1 Some have argued that such moderate reductions in eGFR can occur as the result of normal aging and should not be equated with chronic kidney disease (CKD) in the absence of other abnormalities.2, 3, 4 Others note that reductions in eGFR in the elderly may reflect the high prevalence of kidney disease risk factors at older ages and should not necessarily be considered normal simply because they are common.5

In this issue of the American Journal of Kidney Diseases, Roderick et al6 take a different approach to this issue. Instead of asking whether older patients with moderate reductions in eGFR have or do not have CKD, they ask whether reductions in eGFR in the elderly are associated with a clinically significant outcome, namely, mortality. These investigators address this question by using data collected as part of a randomized trial that compared 2 methods of multidimensional assessment in a representative sample of adults 75 years and older drawn from primary care practices across Britain. More than half the members of this cohort had an eGFR less than 60 mL/min/1.73 m2. Of these, most had mild to moderate decreases in eGFR (45 to 59 mL/min/1.73 m2) and most were women (Fig 1). Baseline characteristics did not differ greatly between those with an eGFR of 45 to 59 mL/min/1.73 m2 and the referent group with an eGFR of 60 mL/min/1.73 m2 or greater, particularly among women. The prevalence of traditional complications of CKD was very low among those with an eGFR ≥ 45 mL/min/1.73 m2. For example, only 1% of women with eGFR of 45 to 59 mL/min/1.73 m2 had hyperphosphatemia and less than 6% had a hemoglobin level less than 11 g/dL. The prevalence of cognitive and functional impairment by comparison was much greater. For example, almost 20% of women with eGFR of 45 to 59 mL/min/1.73 m2 had cognitive impairment, 33% were partially or fully dependent for 2 or more activities of daily living, and 8% had fallen at least twice during the previous 6 months. However, as for many baseline characteristics, these conditions were no more common in this group than in women with eGFR of 60 mL/min/1.73 m2 or greater.

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Figure 1. Distribution of estimated glomerular filtration rates (eGFRs) in men and women cohort members with eGFR less than 60 mL/min/1.73 m2. Conversion factor for GFR in mL/min/1.73 m2 to mL/s/1.73 m2, ×0.01667. Data from Roderick et al.6

Crude death rates were high for all groups, but increased with decreasing eGFR from 8% in those with eGFR of 60 mL/min/1.73 m2 or greater to 21% in those with an eGFR less than 30 mL/min/1.73 m2. Mortality rates were consistently higher and increased more steeply across eGFR categories in men compared with women. Compared with the referent group, absolute mortality rates for those with an eGFR of 45 to 59 mL/min/1.73 m2 were approximately 1% per year higher for women and 3% per year higher for men. After adjustment for baseline characteristics, the risk of all-cause mortality relative to the referent category with an eGFR of 60 mL/min/1.73 m2 or greater was only minimally increased for those with an eGFR of 45 to 59 mL/min/1.73 m2, and this did not reach statistical significance for women. Nevertheless, for both men and women in this group, death was more likely to be from cardiovascular causes than for patients with higher levels of eGFR, particularly if this occurred within the first 2 years of follow-up. The presence of dipstick proteinuria did not contribute substantial additional prognostic information beyond that provided by eGFR. Roderick et al6 conclude that in the elderly, identification and management of CKD should focus on the select group with more severe reductions in eGFR.

Unlike many studies examining the relationship between eGFR and mortality in the elderly, members of the cohort described by Roderick et al6 underwent detailed baseline assessment for both clinical and functional status measures and thus are extraordinarily well characterized. Furthermore, although clinical trial populations are often poorly representative of the general population, this study population was deliberately selected to be representative of older adults in general practice. Nevertheless, some caution is warranted in interpreting the results of this study. Although mortality clearly is an important and reliably ascertained outcome, other clinical outcomes may be more important in the elderly, including hospitalization, nonfatal cardiovascular events, disability, reduced quality of life, cognitive decline, and loss of independence. In addition, because ascertainment of proteinuria was based only on results of dipstick, this study may underestimate the prognostic value of urine protein measurements in this cohort. Finally, as the investigators note, heterogeneity in mortality rates among those with an eGFR of 60 mL/min/1.73 m2 or greater renders estimates of relative risk sensitive to the referent category selected.

Notwithstanding these limitations, the findings reported here are very consistent with results of earlier studies conducted in more broadly defined cohorts showing that the relative risk of death associated with a given level of eGFR is attenuated in the elderly.7, 8, 9, 10 The significance of this finding is that in the elderly, the threshold level of eGFR below which mortality risk exceeds that in the referent category is lower than in younger patients.9, 10 Collectively, these studies raise the question of whether a disease-oriented approach is appropriate for many elderly individuals who meet criteria for CKD. For patients with moderate reductions in eGFR, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) clinical action plan recommends the following strategies: diagnosis and treatment of kidney disease, treatment of comorbid conditions, slowing progression, cardiovascular risk reduction, estimating progression, and evaluating and treating complications.11 However, the value of this approach in older adults with mild to moderate reductions in eGFR is uncertain if most are at no greater risk of death than their age peers with higher eGFRs, do not have a treatable complication of CKD and have a less than a 1% chance per year of progressing to end-stage renal disease (as shown in prior studies).12, 13

Tinetti and Fried14 have noted that disease-oriented models of care evolved in an era when life expectancy was short and determined by dominant disease processes. They argue that management of complex comorbidity in the elderly calls for a more individualized approach to care focused on attainment of patient goals and impacting modifiable processes, both biological and nonbiological.14 Table 1 lists differences between these 2 models of care. It is important to note that an individualized approach does not preclude application of disease-specific treatment strategies when these may impact outcomes of importance to the individual patient.

Table 1. Comparison of Disease-Oriented and Integrated Models of Care

	Disease-Oriented Model	Integrated Individually Tailored Model
	Clinical decision making is focused primarily on the diagnosis, prevention, and treatment of individual diseases.	Clinical decision making is focused primarily on the priorities and preferences of individual patients.
	Discrete pathology is believed to cause disease; psychological, social, cultural, environmental and other factors are secondary factors, not primary determinants of disease.	Health conditions are believed to result from the complex interplay of genetic, environmental, psychological, social, and other factors.
	Treatment is targeted at the pathophysiologic mechanisms thought to cause the disease(s).	Treatment is targeted at the modifiable factors contributing to the health conditions impeding the patient's health goals.
	Symptoms and impairments are best addressed by diagnosing and treating “causative” disease(s).	Symptoms and impairments are the primary foci of treatment even if they cannot be ascribed to a discrete disease.
	Relevant clinical outcomes are determined by the disease(s).	Relevant clinical outcomes are determined by individual patient preference.
	Survival is the usual primary focus of disease prevention and treatment.	Survival is one of several competing goals.

Reprinted from Am J Med, Vol 116, Tinetti ME, Fried T, The end of the disease era, pp 179-185, Copyright 2004, with permission from Elsevier.14

Under the individualized care model, knowing whether an elderly person with moderate reductions in eGFR has CKD assumes less importance than it might under a disease-oriented model. Instead, greater emphasis is placed on assessing each patient's risk of particular outcomes, eliciting which outcomes are most important to the patient, and identifying processes that can be modified. Thus, for example, kidney disease–specific strategies may be very appropriate for an elderly person with an eGFR of 55 mL/min/1.73 m2 who has evidence of progressive loss of kidney function and/or metabolic complications of CKD, particularly if there are no competing health concerns. Conversely, in an elderly person with a stable eGFR of 55 mL/min/1.73 m2 and no complications of CKD, other health concerns may reasonably take precedence.

In conclusion, an individualized model may be more appropriate than a disease-oriented model of care for many elderly people who meet criteria for CKD. Nevertheless the substantial prognostic significance of eGFR in the elderly suggests that it may be very helpful in crafting individualized treatment plans. The clinical utility of this measure could be enhanced further by more studies such as this one, studies that embrace the complexity of how eGFR relates to significant outcomes in older adults in relation to potential modifying factors. The better we understand what eGFR and urinary protein can tell us about what lies in store for our elderly patients, the more helpful these measures will be in the clinical setting.