Elsevier

Ageing Research Reviews

Volume 14, March 2014, Pages 65-80
Ageing Research Reviews

Review
The aging kidney revisited: A systematic review

https://doi.org/10.1016/j.arr.2014.02.003Get rights and content

Highlights

  • Progress in genetics and proteomics has provided new insights on renal aging.

  • Renal aging is a multifactorial process involving several key factors.

  • None of the macroscopic and microscopic features of the aging kidney is pathognomonic of aging.

  • The assessment of renal function in the elderly is problematic and it is still debated whether renal aging should be considered as a physiological or pathological process.

  • Proper lifestyle modifications currently represent the most plausible approach to maintain kidney health.

Abstract

As for the whole human body, the kidney undergoes age-related changes which translate in an inexorable and progressive decline in renal function. Renal aging is a multifactorial process where gender, race and genetic background and several key-mediators such as chronic inflammation, oxidative stress, the renin–angiotensin–aldosterone (RAAS) system, impairment in kidney repair capacities and background cardiovascular disease play a significant role. Features of the aging kidney include macroscopic and microscopic changes and important functional adaptations, none of which is pathognomonic of aging. The assessment of renal function in the framework of aging is problematic and the question whether renal aging should be considered as a physiological or pathological process remains a much debated issue. Although promising dietary and pharmacological approaches have been tested to retard aging processes or renal function decline in the elderly, proper lifestyle modifications, as those applicable to the general population, currently represent the most plausible approach to maintain kidney health.

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.

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