ReviewThe aging kidney revisited: A systematic review
Introduction
Human lifespan has substantially increased over the last century and the projected increase of elderly people over the next two future decades is impressive. Persons aged 65 years or more were 420 million in 2000 (United, 2010). By 2030, the number of these individuals is expected to be 550–973 million (US Census Bureau, 2005). By that date, elderly people will account for approximately 20%, 24.8% and 33% of the global population in the US, China and Europe respectively, exceeding the number of children below 15 years (Centers for Disease Control and Prevention, 2006). The average age is now 76.5 years in economically developed- and 65.4 years in economically developing-countries.
Population based studies documented that impaired renal function is common in the elderly. In the US population, renal dysfunction has a 15% prevalence in persons older than 70 years (Coresh et al., 2007). In the third National Health and Nutrition Examination Survey (NHANES III), 35% of the elderly population had stage 3 chronic kidney disease (CKD) (Coresh et al., 2003). The prevalence of the most severe CKD stage (stage 5 or end-stage kidney disease; ESKD) is age-dependent (Coresh et al., 2003, Kiberd and Clase, 2002). In the United States Renal Data System (USRDS) the prevalence of the age-stratum 65–74 years is 11% and 14% for those older than 75 years (National Institute of Health, 2009) and similar findings have been reported also in European cohorts (John et al., 2004, Jungers et al., 1996, Magnason et al., 2002). In this systematic review we describe the main anatomical and functional changes in the kidney associated with senescence and will provide updated information on the main molecular and biological pathways involved in renal aging. The criteria adopted for literature search and selection for this review are detailed in Fig. 1.
Section snippets
Epidemiology of renal function decline with age
Changes in renal function associated with aging have been estimated in 9 cross-sectional and in 3 cohort studies. In these studies, the annual average GFR reduction ranged from 0.4 to 2.6 mL/min (Table 1). The cross-sectional nature of most of these analyses and the fact that four of them were performed in living kidney donors (Fehrman-Ekholm and Skeppholm, 2004, Poggio et al., 2009, Rule et al., 2004, Rule et al., 2010), a highly selected population where the absence of CKD and other
Issues with assessment of renal function in the elderly
Because sarcopenia and body weight loss reduce the daily generation of creatinine and creatinine levels are influenced by protein intake and hydration, these factors concur in making serum creatinine a suboptimal indicator of renal function in the elderly (Fliser, 2008). The reference range for creatinine considered as normal in the healthy young is inappropriately high in the elderly and serum values in the upper normal range may underlie early renal dysfunction (Kimmel et al., 1996). In 20
Factors associated with renal aging
Renal senescence is a complex, multifactorial process characterized by anatomical and functional changes accumulating during life span. Several factors, spanning from the genetic background to chronic inflammation, exposure to chronic diseases and environmental factors generate a “multi-hit” scenario where the renal phenotype of elderly individuals shows high inter-individual variability (Fig. 2, Fig. 3).
Structural and functional changes in the aging kidney
The main anatomic and functional modifications which characterize the aging kidney are summarized in Fig. 3 and Table 2. Kidney mass progressively increases from birth to the fourth decade of life, peaking at 250–270 g (Zhou et al., 2008a) and gradually regresses thereafter at a 10% reduction rate per decade (Gourtsoyiannis et al., 1990, Long et al., 2005a, Tauchi et al., 1971) (Fig. 4). In the seventh and eighth decades, kidney mass is therefore at least 20–30% less than in the fourth decade (
Future perspectives for retarding renal aging
As briefly alluded to before, dietary interventions to retard systemic and kidney aging have been extensively studied in animal models. Isocaloric diets with low-AGE content reduce kidney and cardiovascular damage associated with age and extend lifespan in rat models (Cai et al., 2007). Furthermore, powerful anti-oxidants, such as the methylglyoxal, potentiate the protective effects of low-AGE diets (Cai et al., 2008). A diet enriched of antioxidants (such as vitamin-E), reduces kidney lipid
Conclusions
Aging has been defined as “the collection of changes that render human beings progressively more likely to die” (Medawar, 1952). This view implies the existence of an inexorable functional decline in biological systems in the whole organism. Whether aging is a disease or as the inevitable consequence of being human is a philosophical and a scientific question. Renal aging is a complex multifactorial process and ascertaining to what extent renal lesions in the elderly represent the life course
Acknowledgments
This review was written as part of the project “Invecchiamento: innovazioni tecnologiche e molecolari per un miglioramento della salute nell’anziano” (PROGETTO BANDIERA 2012–2014). The project received funding by the Italian Ministry of Health.
References (258)
- et al.
Heterogeneity of glomerular size in normal donor kidneys: impact of race
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
(1998) - et al.
The value of a formula including haematocrit, blood urea and gender (HUGE) as a screening test for chronic renal insufficiency
Journal of Nutrition, Health and Aging
(2011) - et al.
Effects of aging on the renal glomerulus
American Journal of Medicine
(1986) - et al.
KLOTHO allele status and the risk of early-onset occult coronary artery disease
American Journal of Human Genetics
(2003) - et al.
Is the diverticulum of the distal and collecting tubules a preliminary stage of the simple cyst in the adult?
Journal of Urology
(1977) - et al.
Protective effect of the inhibition of the renin–angiotensin system on aging
Regulatory Peptides
(2005) Renal responses to acute angiotensin II inhibition and administered angiotensin II in the aging, conscious, chronically catheterized rat
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
(1993)Sexual dimorphism, the aging kidney, and involvement of nitric oxide deficiency
Seminars in Nephrology
(2009)- et al.
Sex and the single kidney
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
(1989) - et al.
Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population
Kidney International
(2000)
Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression
American Journal of Pathology
Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan
American Journal of Pathology
Excessive vasoconstriction after stress by the aging kidney: inadequate prostaglandin modulation of increased endothelin activity
Journal of Laboratory and Clinical Medicine
Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
Tubular cell senescence and expression of TGF-beta1 and p21(WAF1/CIP1) in tubulointerstitial fibrosis of aging rats
Experimental and Molecular Pathology
Hypertension and angiogenesis in the aging kidney: a review
Archives of Gerontology and Geriatrics
Associations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
Sexual dimorphism in the aging kidney: effects on injury and nitric oxide system
Kidney International
Renal function in the elderly: impact of hypertension and cardiac function
Kidney International
The function of hypoxia-inducible factor 1 (HIF-1) is impaired in senescent mice
FEBS Letters
Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects
Kidney International
Falls are associated with decreased renal function and insufficient calcitriol production by the kidney
Journal of Steroid Biochemistry and Molecular Biology
Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation
Kidney International
Determinants of glomerular hypofiltration in aging humans
Kidney International
The influence of age on renal prostaglandin synthesis in man
Prostaglandins, Leukotrienes, and Essential Fatty Acids
Telomere length assessment: biomarker of chronic oxidative stress?
Free Radical Biology and Medicine
A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy
Kidney International
Age-related change in kidney function, its influencing factors, and association with asymptomatic carotid atherosclerosis in healthy individuals – a 5-year follow-up study
Maturitas
Unreferred chronic kidney disease: a longitudinal study
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
Impaired angiogenesis in the aging kidney: vascular endothelial growth factor and thrombospondin-1 in renal disease
American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation
With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging
Cell Metabolism
International Database. Table 094. Mid-year Population, by Age and Sex
Aging-associated changes in renal extracellular matrix
American Journal of Pathology
Effect of acute acid loading on urinary acid excretion by the aging human kidney
Journal of Laboratory and Clinical Medicine
Renal acidification in elderly subjects
Nephron
Trade-offs in the adaptation to acidosis
Kidney International
Association of human aging with a functional variant of klotho
Proceedings of the National Academy of Sciences of the United States of America
Renal prostaglandins, effective renal plasma flow and glomerular filtration rate in healthy elderly subjects
Age and Ageing
Atherosclerotic risk factors and renal function in the elderly: the role of hyperfibrinogenaemia and smoking. Results from the Italian Longitudinal Study on Ageing (ILSA)
Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association – European Renal Association
Urinary concentrating defect in the aged rat
American Journal of Physiology
Disruption of the Ang II type 1 receptor promotes longevity in mice
Journal of Clinical Investigation
Transcriptional regulation of nephrin gene by peroxisome proliferator-activated receptor-gamma agonist: molecular mechanism of the antiproteinuric effect of pioglitazone
Journal of the American Society of Nephrology: JASN
Comparing the Cockcroft–Gault and MDRD equations for calculation of GFR and drug doses in the elderly
Nature Clinical Practice. Nephrology
Renal function, erythropoietin, and anemia of older persons: the InCHIANTI study
Archives of Internal Medicine
Significance of tubulointerstitial changes in the renal cortex for the excretory function and concentration ability of the kidney: a morphometric contribution
American Journal of Nephrology
Hemodynamically mediated glomerular injury and the progressive nature of kidney disease
Kidney International
Age-related cell proliferation and apoptosis in the kidney of male Fischer 344 rats with observations on a spontaneous tubular cell adenoma
Toxicologic Pathology
Angiotensin receptors and aging
Hypertension
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