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| Year : 2010 | Volume
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| Issue : 5 | Page : 835-841 |
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| Chronic kidney disease in older people; Disease or dilemma? |
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Aimun K Ahmed1, Siobhan H.M Brown2, Ahmed H Abdelhafiz2
1 Department of Renal Medicine, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom
2 Department of Elderly Medicine, Rotherham General Hospital, Rotherham, United Kingdom
Click here for correspondence address and email
| Date of Web Publication | 31-Aug-2010 |
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 Abstract | | |
The majority of patients diagnosed with Chronic Kidney Disease (CKD) are elderly and CKD is linked with poor cardiovascular, cognitive, and disability outcomes in these people. Only a minority of these patients will progress to end stage renal disease (ESRD) while the majority will die due to cardiovascular disease. Thus, only a small number of these patients with CKD will benefit from specialist nephrologist assessment. The priority for the remainder should be cardiovascular disease prevention. We have reviewed specific issues relevant to older people to determine high-risk groups with CKD that are likely to benefit from a more intensive risk reduction intervention and to allow identification of clinically relevant renal disease.
How to cite this article:
Ahmed AK, Brown SH, Abdelhafiz AH. Chronic kidney disease in older people; Disease or dilemma?. Saudi J Kidney Dis Transpl 2010;21:835-41 |
How to cite this URL:
Ahmed AK, Brown SH, Abdelhafiz AH. Chronic kidney disease in older people; Disease or dilemma?. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Nov 27];21:835-41. Available from: https://www.sjkdt.org/text.asp?2010/21/5/835/68876 |
| Introduction | |  |
The prevalence of Chronic Kidney Disease (CKD) has been rising and is causing a global challenge as a non-communicable epidemic. In the UK, the prevalence is about 10% of the population, [1] and in people aged over 65 years, this figure reaches 40%. [2] Risk factors predisposing the elderly to CKD remain unknown. However, most analyses show that the majority of patients affected either with microalbuminuria (MA) or with reduced glomerular filtration rate (GFR) are the elderly (> 65 years). [3] Cardiovascular disease (CVD) has a significant impact on CKD in the elderly and affects CKD progression in this age-group. [4] It is well known that renal function declines with age. [5] It is still not clear whether CKD in older people is merely due to age-related changes in kidney function or a genuine kidney disease that will progress to end-stage renal disease (ESRD). Nevertheless, we already know that a minority of elderly patients with CKD will progress to ESRD and that the majority will have morbidity and mortality related to CVD, [6],[7] rather than ESRD. However, labeling older, frail patients with a significant disease can be worrying for them, especially if that will include asking them to travel long distances for specialist secondary and tertiary services. With these above concerns, there has been evolving national and international guidelines to guide primary care physicians and non-renal specialists to refer patients according to the CKD stage. Most of these guidelines have overlooked the age stratification and they have been criticized for building guidance based upon estimated glomerular filtration rate eGFR alone (calculated by The Modification of Diet in Renal Disease [MDRD] equation, which has not been validated in patients above the age of 70 years). [8] Currently, there are no other more accurate methods to estimate GFR in older people with CKD. Another marker which has been found to be superior to serum creatinine in measuring GFR is cystatin C, [9] which may have future implications for older people.
The majority of elderly patients with CKD are in stage three that could well be managed in the community by primary care physicians. The most important issue is to address the high CVD risk in this population which is confounded by the co-existence of CKD. In addition, CVD is known to accelerate CKD progression in elderly subjects. The importance of early detection and prevention has been the focus of many national and international guidelines and standards frameworks. [10] Finding a simple and feasible screening tool for early CKD detection has been an attractive goal.
Microalbuminuria and low GFR are very common in individuals > 65 years, which contributes to the large prevalence of CKD reported in this age-group. There is evidence that MA is a strong predictor of CVD risk in the general population. [11] It is not clear, however, whether MA in early CKD is a marker of kidney damage or widespread CVD including atherosclerosis and peripheral vascular disease, which are not uncommon in the elderly.
| Search Strategy | | |
We performed a search of Medline and Embase from January 1969 to September 2009 using keywords relating to CKD in older people and vascular and renal outcomes. Only English language articles were selected. Articles were reviewed for relevance by abstract. A manual review of citations in retrieved articles was performed in addition to the electronic literature search. The final list of cited references was chosen on the basis of scientific quality and relevance to the topic of review.
| Definition | | |
Chronic Kidney Disease is defined as either a low GFR rate of less than 60 mL/min/1.73 m 2 , or normal GFR plus evidence of kidney damage (most commonly albuminuria, hematuria or abnormal renal ultrasound for three or more consecutive months) regardless of age. [12] The severity of CKD is classified according to the level of GFR, regardless of the etiology, into five stages:
- Stage one: kidney damage with a normal or increased GFR (> 90 mL/min/1.73 m 2 );
- Stage two: kidney damage with a mild decrease in GFR (60-89 mL/min/1.73 m 2 );
- Stage three: a moderate decrease in GFR (30-59 mL/min/1.73 m 2 );
- Stage four: a severe decrease in GFR (15 29 mL/min/1.73 m 2 ) and
- Stage five: kidney failure (< 15 mL/min/1.73 m 2 ).
Older people are particularly susceptible to kidney damage from age-related decline in glomerular filtration as well as kidney damage from chronic disease states such as diabetes mellitus, hypertension, glomerular, and tubulointerstitial disorders. The classification of CKD is applicable to all age-groups despite the fact that GFR gradually declines with age. Whether this decline is part of a normal ageing process is uncertain. Age-related decline in GFR is associated with impaired concentrating ability, global glomerular and vascular sclerosis and tubular atrophy with thinning of renal cortex and reduction in kidney size. These changes are considered pathological if observed in younger individuals. [13],[14]
| Epidemiology | | |
The prevalence and incidence of CKD among older people is increasing. In Europe, the increase in incidence of CKD is age-dependent with incidence rate among patients aged > 75 years being seven times that of patients aged 20-39 years (619 versus 92 new cases per million population) and more than twice that of patients aged 40-59 years (619 versus 264 new cases per million population). [2] The increased incidence of CKD among the elderly translates into a similarly increased prevalence: The Third National Health and Nutrition Examination Survey (NHANES III) of a nationally representative sample of adults in the United States between 1988 and 1994 found that 7.6% of the individuals aged 60-69 years and 25.9% of those aged at least 75 years, had a GFR of 15-60 mL/min/1.73 m 2 , as against only 1.8% of those aged 40-59 years and 0.2% of those aged less than 40 years. [15] In the United States, the number of people diagnosed with ESRD has doubled in the last ten years and a relatively large number of newly diagnosed CKD patients are elderly. [16] In the UK, patients over 65 years of age account for 30% of those on hemodialysis. [17] This increasing trend is also well recognized worldwide. [5]
| Importance of CKD | | |
The importance of CKD is mainly due to its association with cardiovascular disease. In older people, CKD is also linked to the development of cognitive impairment and functional disability. People with CKD are at increased risk of cardiovascular mortality and morbidity as much as those with diabetes. [18] The cardiovascular mortality increases by 11%for each 5 mL/min/1.73 m 2 fall in GFR. [19] In the Rotterdam study, a 10 mL/min/1.73 m 2 decrease in GFR was associated with a 32% increased risk of myocardial infarction (P < 0.001) in 4484 healthy people (mean age, 69.6 years) followed-up for 8.6 years. [20] The cardiovascular health study showed that each 10 mL/min/1.73 m 2 decline in GFR was associated with an adjusted hazard ratio (95% confidence interval [CI]) for cardiovascular disease (CVD), de novo CVD, recurrent CVD and all-cause mortality of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), 1.04 (0.99, 1.09) and 1.06 (1.00, 1.12), respectively in 4893 elderly subjects (mean age 73.4 years). [21] This association between level of CKD and cardiovascular outcome has been shown in another study. [22] However, in this study, patients with renal insufficiency were less likely to receive beneficial therapies, such as aspirin, beta-blockers, thrombolytic therapy, angiography, and angioplasty compared with patients without renal insufficiency, which may have contributed to the worse outcome. There is also association between CKD and cognitive impairment (assessed by Mini-Mental State Examination): Odds ratio 1.32 (95% CI 1.03 to 1.69) for GFR 45 to 59 mL/min/1.73 m 2 and 2.43 (95% CI, 1.38 to 4.29) for GFR < 45 mL/min/1.73 m 2 in an elderly cohort followedup for four years. [23] CKD is also linked with the development of functional impairment in older people, defined as difficulty in walking one-quarter of a mile or climbing ten steps of stairs, independent of co-morbidity and tests of physical performance. The mechanism may be related to a generalized heightened inflammatory state in CKD. [24] There is evidence to suggest that CKD is associated with increased prevalence of both traditional and non-traditional cardiovascular risk factors (elevated fibrinogen, C reactive protein and albuminuria), which suggests that low-grade inflammation is responsible for both vascular disease and CKD. [25] Decreasing GFR was also associated with increased risk of hip fracture in women with CKD compared with women with GFR > 60 mL/min/1.73 m 2 adjusted for age, weight, and calcaneal bone density. The hazard ratio (95% CI) for hip fracture was 1.57 (0.89 to 2.76) in those with GFR 45 to 59 mL/min/1.73 m 2 and 2.32 (1.15 to 4.68) in those with GFR< 45 mL/min/1.73 m 2 (P for trend = .02). [26] Treating cardiovascular risk factors may slow down progression of CKD but it is not known whether this will result in the prevention of decline in cognitive and physical function in older people.
| Albuminuria | | |
GFR is central to the definition and classification of CKD because it is an overall measure of kidney function. However, it has also been shown that most patients with a reduced GFR have fairly stable renal function during follow-up. [27] Therefore, CKD prognosis is de- pendent on associated cardiovascular risk factors or evidence of vascular damage (e.g. microalbuminuria) rather than a measure of kidney function by GFR or cystatin C. It is likely that age-related diffuse atherosclerosis is responsible for renal function decline in certain patients with associated cardiovascular co-morbidities. Concordance between reduced GFR, microalbuminuria and associated cardiovascular and renal risk is not clear. Microalbuminuria increases the risk for cardiovascular events similar to, and independent of, an impaired GFR. [11],[28] The US data show that only 24% of the individuals classified as having CKD Stage three had micro or macroalbuminuria. [29] In a prospective study to determine the combined risk of CVD events and all cause mortality, patients with reduced GFR and microalbuminuria were at increased risk for combined CVD and all cause mortality compared with those with neither condition {hazard ratio (HR) 1.7, 95% C I, 1.1 to 2.4, P = 0.009 respectively}, whereas those with reduced GFR and without microalbuminuria and those without reduced GFR and with microalbuminuria had similar HRs (1.3 and 1.2, respectively). [4] It also appears that microalbuminuria is a determinant factor for developing a renal event (need to start renal replacement therapy) regardless of GFR. In the MRFIT study, the risk of developing a renal event was 12-fold in patients with Stage one CKD with microalbuminuria as compared to patients with no CKD (95% C I 10.3 to 23.9). The risk was only 2.4-fold in Stage three patients without microalbuminuria (95% C I 1.5 to 3.8) and increased to 41-fold in Stage three patients with microalbuminuria (95% CI 15.2 to 71.1). [30] Macroalbuminuria is also a risk marker to identify individuals at risk for accelerated GFR loss. In the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, patients with macroalbuminuria defined as ≥ 300 mg albumin/24 h urine showed a -7.2 mL/min/ 1.73 m 2 GFR loss, compared with -2.3 mL/min /1.73m 2 in the control group (P < 0.001). [31]
The progression of CKD is variable among older patients depending on its severity and on its underlying etiology. In a study to determine the progression of kidney dysfunction among a community based cohort of 10,184 elderly subjects (≥ 66 years) over a median follow-up of 2.0 years, subjects with diabetes mellitus had the greatest decline in GFR of 2.1 mL/min/1.73 m 2 and 2.7 (95% CI 2.3-3.1) per year in women and men respectively (95% CI 1.8-2.5), in comparison to 0.8 (95% CI 0.6-1.0) and 1.4 (95% CI 1.2-1.6) mL/min/1.73 m 2 per year for women and men without diabetes mellitus. Subjects with a mean GFR < 30 mL/min/1.73m 2 with and without diabetes, experienced the greatest decline in GFR. [32] Hypertension was another determinant of decline in GFR among 2181 men and women enrolled in the placebo arm of the Systolic Hypertension in the Elderly Program (SHEP) study. The decline in kidney function was defined as an increase in serum creatinine equal to or greater than 35 μmol/L over five years of follow-up. Elevated systolic blood pressure (SBP) imparted the highest risk of decline in kidney function. The adjusted relative risk (95% CI) associated with the highest compared with the lowest quartile of BP was 2.44 (1.67 to 3.56) for systolic, 1.29 (0.87 to 1.91) for diastolic, 1.80 (1.21 to 2.66) for pulse, and 2.03 (1.39 to 2.94) for mean arterial pressure. [33] Studies based on patients referred for specialist care showed higher rates of decline in GFR of 7-8 mL/min/year. [34] Results from community based reports indicate a much lower rate of progression of CKD in the elderly. The Baltimore longitudinal study on aging [35] reported an average decline in creatinine clearance of 0.75 mL/min/year after the third decade of life, with approximately one third of subjects demonstrating stable kidney function over 20 years of followup. Another study showed decline of GFR by 1.05 mL/min/year in the very elderly aged 70 to 110 years old. [36] Results from the cardiovascular health study also indicate little or no progression of CKD in the majority of older people (> 26.5 micromol/L in less than 3% of the subjects, mean age 73 years) over three years. [37] There is a low rate of progression to ESRD in most elderly patients (those without recurrent acute kidney injury or cardiovascular co-morbidities) with CKD.7 However, diabetes mellitus [32] and systolic hypertension [33] have the highest impact on progression of CKD in older people and the course of the disease can be modulated by treating these cardiovascular risk factors. Mortality is a more common outcome than the need for initiating renal replacement therapy in this group. In a large study of 27,998 patients with GFR less than 90 mL/min/1.73m 2 followed-up for five years, the rate of renal replacement therapy initiation was 1.1%, 1.3% and 19.9% respectively for CKD Stages two, three and four, but the mortality rate was 19.5%, 24.3% and 45.7% respectively. [6] In a Norwegian prospective study, 3069 out of 65,604 people (≥ 20 years old) were identified to have CKD. During the eight years follow-up, only 38 (12%) of the 3069 people with CKD progressed to ESRD, and the risk was especially low in people without diabetes or hypertension, women, and those aged ≥ 70. In contrast, there was high cardiovascular mortality: 3.5, 7.4, and 10.1 deaths per 100 person years among people with a GFR of 45-59, 30-44 and < 30 mL/min/1.73 m 2 , respectively. [7]
Age is a major effect modifier among patients with CKD. O'Hare et al [38] investigated age-specific incidence of death, treated ESRD, and change in GFR among 209,622 US veterans with CKD Stages three to five followed up for a mean of 3.2 years. Among patients of all ages, rates of both death and ESRD were inversely related to GFR at baseline. However, among those with comparable levels of GFR, older patients had higher rates of death and lower rates of ESRD than younger patients. The level of GFR below which the risk of ESRD exceeded the risk of death varied with age, ranging from 45 mL/min/1.73 m 2 for patients aged 18 to 44 years to 15 mL/min/1.73 m 2 for patients aged 65 to 84 years. Among those 85 years or older, the risk of death always exceeded the risk of developing ESRD. Among patients with GFR levels < 45 mL/min/1.73 m 2 at baseline, older patients were less likely than their younger counterparts to experience an annual decline in GFR of > 3 mL/min/1.73 m 2 . In another study to assess survival of 129 elderly patients (≥ 75 years) with CKD Stage five, managed either with dialysis or conservatively, one and two year survival rates were 84% and 76% in the dialysis group (n=52) and 68% and 47% in the conservatively managed group (n=77), respectively (P < 0.001). However, this survival advantage was lost in those patients with high co-morbidity scores, especially when the co-morbidity included ischemic heart disease. [39] This reduction in survival by associated co-morbidity was also shown in octogenarians and nonagenarians newly starting dialysis. One year mortality after dialysis initiation was 46%. Median (interquartile range) survival after dialysis initiation was 15.6 months (4.8 to 35.5) for patients 80 to 84 years of age, 11.6 months (3.7 to 28.5) for patients 85 to 89 years of age, and 8.4 months (2.8 to 21.3) for patients ≥ 90 years old. Clinical characteristics strongly associated with death were older age, no ambulatory status, and more co-morbid conditions. [40]
| Conclusions | | |
The majority of patients diagnosed with CKD are elderly. However, there are considerably fewer older patients on chronic dialysis than patients in the earlier stages of CKD. The majority of older people seem to have no or minimal progression of kidney disease. The number of CKD patients progressing to renal failure that requires replacement therapy is much lower than the number of patients who die before they reach that point, largely due to cardiovascular disease. This therefore suggests that our approach to manage CKD in older people should not be based on disease stage alone. It appears that patients with Stage one and two CKD with microalbuminuria are at a greater risk than patients in Stage three without microalbuminuria. Therefore, screening for CKD should not only focus on looking for reduced GFR but also should include measurement of albuminuria. Strategies aimed at slowing progression of kidney disease should consider underlying risk factors for progression and the negligible loss of kidney function that occurs in the majority of older patients with CKD. Low-risk patients can be managed by Geriatricians or General Practitioners [Table 1].[41] High-risk patients can be identified by the presence of diabetes mellitus, systolic hypertension, microalbuminuria and low GFR < 30 mL/min/1.73 m2. These patients are likely to receive the maximum benefit from intensive treatment of their cardiovascular risk factors and should be targeted for renal specialist multi-disciplinary care input. | Table 1 :Criteria for CKD management by general practitioner or nephrologist.41
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Correspondence Address:
Ahmed H Abdelhafiz
Consultant Geriatrician and Honorary Senior Clinical Lecturer, Department of Elderly Medicine, Rotherham General Hospital,Moorgate Road, Rotherham, S60 2UD
United Kingdom
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PMID: 20814116 
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