Managing End-Stage Renal Disease in the Elderly
Managing End-Stage Renal Disease in the Elderly
With progressive aging, the kidney undergoes anatomical and physiological changes due to either organ senescence or other specific diseases, such as atherosclerosis or diabetes that are highly prevalent in the elderly.
Several studies have demonstrated increased rate of sclerotic glomeruli with aging. In kidney biopsies from older individuals, light microscopy generally shows nephrosclerosis (glomerulosclerosis, arteriosclerosis, tubular atrophy and interstitial fibrosis that occur commonly together) and other histomorphometric changes, such as increased glomerular size (due to compensatory hypertrophy of unaffected nephrons) and decreased glomerular density (as expressed by the number of glomeruli per area of cortex).
Nephrosclerosis and lower glomerular density both contribute to GFR decline in the elderly. Rowe et al. demonstrated an accelerated decline in endogenous creatinine clearance in 293 healthy subjects with advanced age, and concluded that this decline was a 'physiological' renal aging (i.e., not secondary to other diseases that are highly prevalent in the elderly, such as arteriosclerosis and diabetes). However, many years later, Fliser et al. demonstrated that GFR decline in the elderly might be deeply influenced by lifetime exposure to several conditions, including obesity, hypertension, congestive heart failure, and diabetes, and appropriate treatment and/or control of these factors might actually reduce the rate of vascular and interstitial sclerosis, and therefore slow the decline of kidney function over time. On the other hand, the slope of GFR decline is generally mild in older patients with fewer comorbidities, whose kidneys preserve the ability to respond to acute hemodynamic changes and retain essential physiological functions.
In recent years, significant efforts have been made to estimate GFR by using different equations, including the recent CKD Epidemiology Collaboration formula. Unfortunately, a growing body of evidence indicates that estimation formulae are often unreliable in both diabetic and nondiabetic patients. Since the majority of epidemiological studies assessing the burden of CKD are based on estimated GFR (eGFR), using these formulas for accurate staging of CKD is still a matter of lively debate, particularly in older patients. The ongoing Berlin Initiative Study will help to better establish the boundaries of 'normal' GFR in older patients and to address the issue of proper CKD diagnosis in older individuals, by using iohexol clearance as the gold standard to estimate GFR accurately and precisely. With these caveats in mind, a recent individual-level meta-analysis, including over 2,000,000 individuals, demonstrated that reduced eGFR values and increased albuminuria were independently associated with mortality and ESRD, regardless of age, across a wide range of populations. In addition, moderate eGFR reduction in older individuals with hypertension and low risk of renal disease progression have been associated with a significant burden from CV disease and a significantly lower burden of ESRD. Indeed, given the presence of competing factors, such as death for CV disease before developing ESRD, patients with either stage 3A CKD or aged 65–79 years or older have a much lower risk for incident ESRD compared with patients with stage 3B/4 CKD or aged less than 65 years, respectively. It has been suggested that a different eGFR threshold (<45 ml/min/1.73 m) might achieve a better evaluation of the risk of progression to ESRD and a lower risk of misclassification of CKD stage.
Pathophysiology
With progressive aging, the kidney undergoes anatomical and physiological changes due to either organ senescence or other specific diseases, such as atherosclerosis or diabetes that are highly prevalent in the elderly.
Several studies have demonstrated increased rate of sclerotic glomeruli with aging. In kidney biopsies from older individuals, light microscopy generally shows nephrosclerosis (glomerulosclerosis, arteriosclerosis, tubular atrophy and interstitial fibrosis that occur commonly together) and other histomorphometric changes, such as increased glomerular size (due to compensatory hypertrophy of unaffected nephrons) and decreased glomerular density (as expressed by the number of glomeruli per area of cortex).
Nephrosclerosis and lower glomerular density both contribute to GFR decline in the elderly. Rowe et al. demonstrated an accelerated decline in endogenous creatinine clearance in 293 healthy subjects with advanced age, and concluded that this decline was a 'physiological' renal aging (i.e., not secondary to other diseases that are highly prevalent in the elderly, such as arteriosclerosis and diabetes). However, many years later, Fliser et al. demonstrated that GFR decline in the elderly might be deeply influenced by lifetime exposure to several conditions, including obesity, hypertension, congestive heart failure, and diabetes, and appropriate treatment and/or control of these factors might actually reduce the rate of vascular and interstitial sclerosis, and therefore slow the decline of kidney function over time. On the other hand, the slope of GFR decline is generally mild in older patients with fewer comorbidities, whose kidneys preserve the ability to respond to acute hemodynamic changes and retain essential physiological functions.
In recent years, significant efforts have been made to estimate GFR by using different equations, including the recent CKD Epidemiology Collaboration formula. Unfortunately, a growing body of evidence indicates that estimation formulae are often unreliable in both diabetic and nondiabetic patients. Since the majority of epidemiological studies assessing the burden of CKD are based on estimated GFR (eGFR), using these formulas for accurate staging of CKD is still a matter of lively debate, particularly in older patients. The ongoing Berlin Initiative Study will help to better establish the boundaries of 'normal' GFR in older patients and to address the issue of proper CKD diagnosis in older individuals, by using iohexol clearance as the gold standard to estimate GFR accurately and precisely. With these caveats in mind, a recent individual-level meta-analysis, including over 2,000,000 individuals, demonstrated that reduced eGFR values and increased albuminuria were independently associated with mortality and ESRD, regardless of age, across a wide range of populations. In addition, moderate eGFR reduction in older individuals with hypertension and low risk of renal disease progression have been associated with a significant burden from CV disease and a significantly lower burden of ESRD. Indeed, given the presence of competing factors, such as death for CV disease before developing ESRD, patients with either stage 3A CKD or aged 65–79 years or older have a much lower risk for incident ESRD compared with patients with stage 3B/4 CKD or aged less than 65 years, respectively. It has been suggested that a different eGFR threshold (<45 ml/min/1.73 m) might achieve a better evaluation of the risk of progression to ESRD and a lower risk of misclassification of CKD stage.
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