Is Chronic Kidney Disease in Older People a New Geriatric Giant?

Ahmed H Abdelhafiz; Shameela Ahmed; Katie Flint; Meguid El Nahas

Aging Health. 2011;7(5):749-762.

Abstract and Introduction

Abstract

The global population is aging, and the number of people above the age of 85 years is growing faster than any other age group. There is an age-related decline in kidney function; however, not all individuals will develop chronic kidney disease (CKD) with advancing age. Those who are genetically predisposed and exposed to lifetime cardiovascular risk factors are likely to develop systemic atherosclerosis and CKD as a part of its manifestation. CKD promotes poor health through its association with inflammation and oxidative stress. Malnutrition, weight loss and sarcopenia are common in CKD patients, leading to poor outcomes, such as physical and cognitive dysfunction, manifesting as major geriatric syndromes. Frailty is likely to be one of the underlying processes that leads to the clinical manifestations of geriatric syndromes in patients with CKD. Therefore, functional outcomes, such as cognition and physical functioning, might be more relevant outcomes to older patients with CKD. Interventions should be developed and assessed in terms of maintaining quality rather than quantity of life before disability develops.

Introduction

The elderly population is growing. In 2003, people aged over 65 years comprised 12% of the total population of the USA. This number is projected to increase to 20% in 2030. In addition, patients aged over 85 years represented 1.6% of the total population of the USA in 2003, but they are projected to double by 2030 and to double again by 2050.^[1] As life expectancy increases, more elderly patients are surviving longer with chronic conditions in particular cardiovascular disease and chronic kidney disease (CKD). Age may be interpreted as an increased risk of exposure time to traditional cardiovascular risk factors, such as smoking, diabetes, dyslipidaemia and a sedentary lifestyle. Thus, the increase in cardiovascular disease in older people can be viewed as an interaction between age (exposure time), cardiovascular risk factors and genetic factors.^[2] Individuals with both genetic and environmental risk factors for cardiovascular disease develop age-related vascular pathology with diffuse atherosclerosis (unsuccessful aging). On the other hand, successful aging could be defined as aging with lesser dysfunction and without the development of major chronic diseases.^[3] This implies that glomerular filtration rate (GFR) may decline physiologically with age without evidence of renal dysfunction, while CKD with evidence of renal damage, such as albuminuria, is likely to be a manifestation of broader age-related diffuse vascular damage, affecting a number of end organs, including the heart, kidneys, brain and eyes.^[4] Therefore, advanced age alone is not responsible for kidney damage or a primary renal disease but its coexistence with other comorbid conditions, such as hypertension, diabetes and atherosclerosis, may accentuate such damage.^[5] The pathophysiologic mechanisms underlying age-related decline in kidney function, the interactions between age and other risk factors in renal function progression, and the associations of CKD with other comorbidities common in old age are less clear. This article summarizes age-related renal and vascular changes and renal function assessment, and explores the systemic nature of CKD and its association with geriatric syndromess mainly physical and cognitive dysfunction in older people.

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Table 1. Effect of chronic kidney disease on physical function.
Parameter	eGFR <30 ml/min/1.73 m²; odds ratio (95% CI)	eGFR 30–44 ml/min/1.73 m²; odds ratio (95% CI)	eGFR 45–59 ml/min/1.73 m²; odds ratio (95% CI)	p-value
Dependence in ADL	2.16 (1.42–3.30)	1.60 (1.20–2.14)	1.04 (0.86–1.25)	<0.001
Lack of physical activity	2.20 (1.39–3.48)	1.78 (1.37–2.32)	1.10 (0.92–1.32)	<0.001
Falls	2.04 (1.26–3.31)	1.06 (0.78–1.43)	1.02 (0.82–1.26)	0.006

ADL: Activities of daily living; eGFR: Estimated glomerular filtration rate.
Data taken from [32].

Table 2. Effect of chronic kidney disease on physical function compared with other chronic comorbidities.
Parameter	CKD; mean (SE)	Heart failure; mean (SE)	COPD; mean (SE)	High CV risk; mean (SE)
SPPB score (0–12)	8.42 (0.30)	9.92 (0.24), p= 0.0003	10.17 (0.18), p < 0.0001	10.18 (0.11), p < 0.0001
Grip strength (kg)	24.4 (1.7)	36.2 (1.8), p < 0.0001	36.2 (0.8), p < 0.0001	38.0 (0.7), p < 0.0001
Gait speed (m/s)	0.80 (0.04)	1.20 (0.03), p < 0.0001	0.96 (0.02), p = 0.0053	1.22 (0.02), p < 0.0001

CKD: Chronic kidney disease; COPD: Chronic obstructive pulmonary disease; CV: Cardiovascular; SE: Standard error; SPPB: Short physical performance battery.
Data taken from [51].

Table 3. Effect of chronic kidney disease on physical function: prediction of frailty by severity of chronic kidney disease compared with no chronic kidney disease.
Parameter	CKD stage 1–2	CKD stage 3a	CKD stage 3b–4–5
Prevalence of frailty; % (standard error)	5.94(0.99)	10.74(2.36)	20.90 (3.44)
Odds ratio (59% CI)	2.21 (1.49–3.28)	2.48 (1.57–3.93)	5.88 (3.40–10.16)

CKD: Chronic kidney disease.
Data taken from [59].

Table 4. Effect of chronic kidney disease on cognitive function: prevalence of cerebral small-vessel disease in chronic kidney disease.
Parameter	High cystatin levels^†; odds ratio (95% CI)	High cystatin levels and albuminuria^‡; odds ratio (95% CI)
Lacunar infarctions	2.7 (1.6–4.5), p < 0.01	2.8 (1.5–5.4), p < 0.01
White matter lesions	1.7 (1.0–2.9), p < 0.05	2.1 (1.1–4.1), p < 0.05

†Compared with low cystatin levels.
‡Compared with low cystatin levels and no albuminuria.
Data taken from [61].

Table 5. Effect of chronic kidney disease on cognitive function: prevalence and prediction of cognitive impairment by severity of chronic kidney disease.
Parameter	eGFR >60 ml/min/1.73 m²	eGFR 45–59 ml/min/1.73 m²	eGFR <45 ml/min/1.73 m²
Prevalence of cognitive impairment at baseline (%)	9.3	15.4	22.2
Odds ratio (95% CI) of cognitive impairment at baseline	1.0	1.16 (0.82–1.63), p = 0.4	1.28 (0.83–1.98), p = 0.3
Incidence of new cognitive impairment after 2 years of follow-up (%)	5.8	9.9	21.5
Odds ratio (95% CI) of cognitive impairment after 2 years of follow-up	1.0	1.12 (0.69–1.82), p = 0.7	2.14 (1.18–3.87), p = 0.01

eGFR: Estimated glomerular filtration rate.
Data taken from [65].

Table 6. Performance in the lowest quartile of cognitive scores for persons with chronic kidney disease: mental performance in persons with chronic kidney disease compared with no chronic kidney disease.
Cognitive measure	Basic model; odds ratio (95% CI)^†	Basic model + cardiovascular disease risk factors + stroke; odds ratio (95% CI)^‡
Global composite	2.27 (1.47–3.52), p = 0.0002	1.97 (1.25–3.10), p = 0.0035
Visual–spatial organization and memory	2.00 (1.31–3.07), p = 0.0016	1.88 (1.21–2.93), p = 0.0052
Scanning and tracking	2.01 (1.30–3.12), p = 0.0018	1.83 (1.56–2.87), p = 0.0094

†Adjusted for age, sex, education and race.
‡Adjusted for age, sex, education, race, diabetes, systolic blood pressure, BMI, cigarettes/day, high-density lipoprotein cholesterol and stroke.
Data taken from [70].

Box 1. Age-related anatomic/physiologic renal and vascular changes.
Renal changes Decreased renal mass Decreased number of glomeruli Increased glomerular sclerosis Increased tubulo–interstitial fibrosis, scarring and atrophy Reduced tubular mass Decreased renal blood flow Increased vascular thickness and hyalinosis Increased renal vascular resistance Vascular changes Increased intimal thickness Reduced elastin content of the media Vascular dilatation and stiffening Loss of compliance of large arteries Increased pulse wave velocity Wide pulse pressure

Box 2. Effect of chronic kidney disease on physical function.
Functional limitation Difficulty in walking and climbing Slow gait speed Reduced balance Increased chair-rise time Increased risk of falls Reduced physical activity Impaired home management Decreased social interaction Reduced self-care Low grip strength Sarcopenia Increased risk of osteoporosis and fractures Dependency in activities of daily living Increased risk of frailty and disability

Box 3. Effect of chronic kidney disease on cognitive function.
Cerebral small-vessel disease Lacunar infarctions Stroke White matter lesions Low mini-mental state examination scores Prolonged event-related potential latencies Reduced global cognition, intelligence, memory, attention and executive function Deficits in visual–spatial organization, naming, scanning and tracking

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Executive Summary

Introduction

More older people are surviving longer with chronic conditions, such as cardiovascular disease and chronic kidney disease (CKD).
Systemic atherosclerosis associated with chronic medical conditions leads to unsuccessful aging.

Effect of Age on the Kidney & Vasculature

Aging is associated with loss of renal mass, glomerulosclerosis, tubular atrophy and increased arterial stiffness.

Kidney Function Assessment

Serum creatinine is an insensitive marker of renal function in the elderly and estimation of glomerular filtration rate is the current recommended method.

Prevalence of CKD

Prevalence of CKD is increasing, particularly in those older than 75 years.
Prevalence of CKD is much higher in institutionalized older people.

CKD & Vascular Outcome

CKD increases the risk of mortality from cardiovascular disease, which outweighs the risk of progression to end-stage renal disease.

CKD & Physical Function

CKD is associated with functional limitation, osteoporosis, falls and fractures.
Dependency in activities of daily living, disability and frailty are important functional outcomes of CKD.

CKD & Cognitive Function

CKD is associated with cerebral small vessel disease, infarctions, white matter lesions and strokes.
Cognitive decline can be the end result, particularly impairment of executive function.

Discussion

CKD is associated with geriatric syndromes, mainly a decline in physical and cognitive function.
Severity of geriatric syndromes is proportional to the severity of CKD.
Frailty, associated with CKD, is likely the underlying process that leads to the clinical manifestations of geriatric syndromes.

Conclusion

CKD is a new geriatric giant significantly related to cognitive and physical disabilities in older people.

Future Perspective

Reduced GFR and/or albuminuria may provide evidence of the risk of developing future disability.
More studies are needed to test the impact of therapeutic interventions in reducing frailty and dependency in patients with CKD.