QJM Advance Access originally published online on August 12, 2006
QJM 2006 99(9):595-599; doi:10.1093/qjmed/hcl075
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Age-related differences in renal function at onset of renal replacement therapy in chronic kidney disease stage 5 patients
From the Divisions of 1Geriatrics and 2Nephrology, Department of Internal Medicine, University of Virginia Health System, Charlottesville, USA
Address correspondence to Dr S.A. Balogun, Division of Geriatrics, Department of Internal Medicine, University of Virginia Health System, PO Box 800506, Charlottesville, VA 22908–0506, USA. email: sab2s{at}virginia.edu
Received 31 May 2005 and in revised form 8 May 2006
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Background: Guidelines for initiating renal replacement therapy (RRT) are based on renal function and not age, so renal function at onset of RRT is expected to be similar across age groups.
Aim: To evaluate renal function at initiation of RRT across age groups.
Design: Observational cross-sectional study.
Methods: We extracted data for all incident chronic kidney disease (CKD) stage 5 patients (n = 322 064) commenced on chronic dialysis (haemodialysis and peritoneal) and renal transplant in the US from 1995 to 1999 from the US Renal Data Systems (USRDS). Subjects (n = 662) with incomplete data were excluded. The reminder (n = 321 402) were classified into five age groups: 0–19 years; 20–44 years; 45–64 years; 65–74 years; 
75 years. Mean values of serum creatinine (Cr, mg/dl), creatinine clearance (CrCl, ml/min), body weight (kg) and body mass index (BMI, kg/m2) at onset of RRT were computed. Mean daily urinary creatinine excretion per kg body weight (CrCl x Cr/0.07/weight) was also calculated.
Results: Progressively lower serum creatinine levels were found in adult patients with increasing age (10.70, 8.56, 7.38 and 6.88 mg/dl in those aged 20–44 years, 45–64 years, 65–74 years, 75 years, respectively). CrCl was also lower in the same groups (14.76, 13.38, 11.63 and 11.60 ml/min, respectively).
Discussion: Older patients have a greater reduction in renal function than younger patients at onset of RRT, suggesting a delay in initiation of therapy.
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Introduction |
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Renal replacement therapy (RRT) in the US is mostly provided by haemodialysis, and to a lesser extent through peritoneal dialysis and renal transplantation. In recent years, it has been common in the US to initiate RRT in adults whose serum creatinine is
8 mg/dl, or whose creatinine clearance (CrCl) is <10 ml/min (6 mg/dl or 
15 ml/min in diabetics). This is the threshold at which additional documentation would not be needed for Medicare reimbursement of the cost of RRT, as contained in Public Law 92– 603, enacted by the US congress in 1973.1 This law made end-stage renal disease (ESRD) now called chronic kidney disease (CKD) stage 5, the only medical condition that would make Americans qualify for Medicare reimbursement regardless of age. The lack of proven objective medical indications to start RRT made this administrative criterion for reimbursement a commonly used guide for initiation of RRT,2 with supposedly no discrimination based on age or gender. On this basis, it might be expected that renal function among incident CKD stage 5 patients starting RRT would be similar across age groups; however, this is not the case.2–7 Elderly CKD patients on dialysis are known to have worse overall outcomes than their younger counterparts.8,9 Advanced age and other factors such as malnutrition, severity of renal disease and co-morbidities have been thought to greatly contribute to the observed differences in mortality following RRT.8–10 However the association between age and severity of renal disease at onset of RRT has not been well studied. We investigated whether renal function at initiation of RRT varied with age.
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Methods |
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This was a cross–sectional study of all incident CKD stage 5 patients (n = 322 064) commenced on chronic dialysis (haemodialysis and peritoneal) and renal transplant in the US from 1995 to 1999. Patients who received dialysis for <90 days (for acute renal failure) were not included.
Data were obtained from the US Renal Data Systems (USRDS), a national database of all CKD stage 5 patients about to receive chronic RRT. Data, including serum creatinine level, creatinine clearance (derived from 24-h urine collection), weight, height, body mass index, age, sex and race are prospectively collected and abstracted from standardized forms (ESRD Medical Evidence Medicare Entitlement Form, HCFA-2728). For the purpose of this study, the data collected directly from the USRDS database were the mean serum creatinine levels (Cr, mg/dl), mean creatinine clearance levels (CrCl, ml/min), mean body weight (kg), and mean body mass index (BMI, kg/m2) of all subjects, already divided according to age groups.
The creatinine clearance levels of subjects in the USRDS database are derived from 24-h urine collection; patients with CKD stage 5 typically have this done for an accurate estimation of their renal function before starting RRT.
Only 662 subjects had incomplete data. Because they were so few (0.2% of total), they were excluded from analysis. The reminder (n = 321 402), with complete data, were classified into five age groups: 0–19 years; 20–44 years; 45–64 years; 65–74 years; 75 years. Mean daily urinary creatinine excretion per kg body weight (CrCl x Cr/0.07/weight) was calculated for each age group, to give a better estimation of renal function than creatinine clearance by adjusting for differences in body weight.
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Demographic characteristics
The mean age was 50.6 years (range 1–88 years). Patients aged
65 years accounted for almost half (47.8%) the total number, while those aged <20 years of age accounted for the smallest proportion (1.3%) (Table 1). There were slightly more men than women (53.2% vs. 46.8%). Some 61.8% were White, 29.4% were Black, 2.3% were Hispanic, 1.5% were Native American, and 5% lacked such information, and were categorized as unknown.
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Renal function and other parameters at RRT initiation
Renal function, as indicated by CrCl and daily urinary excretion of creatinine per kg body weight, varied significantly across age groups (Table 2). Overall, CrCl was lower in patients aged
65 years (11.63 for 65–74 years, 11.6 for >75 years). The 65–74 years and 75 years age groups did not show significantly different creatinine clearances. Patients starting RRT aged 65 years had the lowest CrCl of any age group aged >19 years. These differences persisted even after correction for differences in body weight, with the calculated daily urinary excretion of creatinine per kg body weight (17.10 for 65–74 years, 17.34 for 75 years), again with little difference between the 65–74 years and 75 years groups.
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Body weight was highest among those aged 45–64 years, falling in subsequent age groups. Although CrCl was lowest in the 0–20 years age group, when adjusted for body weight, CrCl at the time of RRT initiation was lowest among those aged 65 years and older.
In contrast to the observed decrease in CrCl associated with advancing age in the study population, mean values of serum creatinine, which are expected to rise in association with worsening renal function, were actually lowest (mean Cr 6.88) in the oldest group of patients beginning chronic RRT (Figure 1). These lower serum creatinine levels in the elderly (65 years) cannot be fully explained by lower lean body mass. Body mass index and other nutritional parameters affect only 1% of total variance in creatinine levels across different age groups.6 Lower mean Cr in the elderly, with concomitant lower calculated daily urinary creatinine excretion per kg body weight, suggests greater renal impairment in these patients, compared to younger age groups with similar BMI.
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Discussion |
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In this study of all incident CKD stage 5 patients treated beyond 90 days in the US, the severity of renal failure prior to the initiation of RRT varied with age, older patients starting RRT having less renal function than younger patients. Since overall survival may be associated with disease severity,8–10 at least some of the previously reported age-related difference in survival associated with RRT might be attributable to differences in the severity of renal disease, rather than to the effects of aging alone. In other words, the association between age and survival in dialysis patients may be confounded by disease severity at initiation of RRT.
Although some nations restrict or prohibit the use of RRT in older patients, there are no such age restrictions in the US, where eligibility for RRT is based primarily on the severity of renal disease. Consequently, one would expect the severity of renal failure at the time that RRT is begun to be similar across all age groups in this country, particularly since the overall success of treatment is possibly related to the timing of RRT initiation.11 The fact that renal function at RRT onset varies as a function of age is therefore surprising, if not disturbing. It suggests that initiation of RRT is delayed in older patients and that factors other than the severity of renal disease (in effect, the only eligibility requirement of Medicare and other third-party payers), determine the timing of RRT initiation. Naturally, the possibility of age bias has to be considered, however the fact that renal function at RRT onset fell throughout adulthood from age 45 onwards mitigates against bias against the elderly per se as a determining factor.
Older age may potentially be associated with different patient attitudes toward RRT, such that many older patients might opt against RRT or delay treatment themselves. However, considering that >150 000 Americans aged 65 years received RRT in this study, representing nearly 50% of such patients, it seems unlikely that older patients prefer to avoid dialysis more than younger patients do.
Age has been identified as a factor associated with delayed referral to a nephrologist in patients with ESRD.12,13 Patients aged >55 years were five times more likely to be referred late compared to younger patients.13 Patients referred late to nephrologists are at greater risk of poor outcomes, including death.12,14–16
The effect on mortality of residual kidney function per se at initiation of RRT in elderly (65 years and above) patients remains largely unknown. A few studies have suggested that there is no clinically significant negative impact on survival,21,22 but the subjects in these studies were largely younger than 65 years.
Another notable finding of this study was that the presumed inverse association between age and serum creatinine at onset of RRT was confirmed within a large cohort of patients. Serum creatinine concentration is dependent on the balance between production (muscle metabolism and to a lesser extent dietary meat) and excretion in the urine.2 Because of age-related changes in body composition characterized by a reduction in lean body mass, production of serum creatinine is diminished with age. Thus, at any given level of renal function, serum creatinine (Cr) is lower in older patients. Similarly, Cr levels have been shown to have a very weak correlation with renal function, especially among women, who generally have less muscle mass than men.17 Reliance on Cr alone as an indicator of renal function underestimates the severity of renal impairment in older patients.
The National Kidney Foundation guidelines for chronic kidney disease suggest estimation of renal function with either the Modification of Diet in Renal Disease (MDRD) Study Equation—Levey formula (Figure 2) or the Cockcroft-Gault formula (Figure 3).18 Both equations are better at estimating renal function than serum creatinine in these patients, as they incorporate certain clinical variables such as age, sex, body weight that affect serum creatinine concentration and ultimately, renal function.23 Both, however, have their limitations in the elderly population.
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The Cockcroft-Gault equation was developed from a study with about 200 male subjects with normal serum creatinine levels, it adjusts for patients’ age and weight, in addition, there is a theoretical adjustment factor for women based on lower muscle mass. The MDRD study equation is more accurate in assessing renal function than the Cockcroft-Gault equation, and was developed primarily in individuals aged <70 years. It incorporates the age, ethnicity and sex of individuals (Figure 2) but has not been validated in those at either extreme of body size (very thin or obese) or aged >70 years.23,24 It is probable that neither equation can accurately measure renal function in individuals with conditions not included in the population studied in developing these equations. Creatinine clearance estimation from a 24-h urine collection is probably the most accurate method in elderly patients, but this can often prove very difficult because of functional or cognitive limitations. As such, despite the limitations of the Cockroft-Gault and MDRD equations, they have a major advantage in that they can easily be implemented. Clinicians can encourage the clinical laboratories serving their patients to automatically compute estimates of renal function with either of these formulae.
The most likely explanation for our findings is that clinicians who rely on Cr alone fail to recognize the severity of their older patients’ disease, and therefore fail to refer their older patients for appropriate treatment in a timely manner. If RRT is considered appropriate therapy for CKD stage 5 regardless of age, some kind of intervention on a national scale may be necessary to ensure the timely initiation of appropriate therapy. Continued efforts to educate physicians about ageing physiology and other basic principles of good geriatric medicine might be considered, given the inadequacy of geriatric training in medical school and residency training programs nationwide.19
It is difficult to overemphasize the importance of this issue in the US, where nearly half of all patients currently receiving RRT are aged 65 years,3–7 and the overall population of that age group is expected to increase by >50% in <30 years.20 The care of older patients with renal failure will of necessity require greater awareness on the part of physicians in the coming years.
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An abstract of this paper was presented at the American Society of Artificial Internal Organs Annual Meeting in Washington, DC, June 2003. The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government.
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