The Kidney in Normal Aging

Denic, Aleksandar; Glassock, Richard J.; Rule, Andrew D.

doi:10.2215/cjn.10580821

Cited by 25 publications

(16 citation statements)

References 11 publications

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“…The word senescence can refer to either cellular senescence or to senescence of the whole organism. Kidney senescence has been well described at the cellular and microscopic levels, with a distinction between the microstructural changes observed in normal physiologic aging versus in diseases (1,2). The effect of kidney senescence on GFR has been relatively well described but mainly from cross-sectional data, which are not ideal from a methodologic point of view (1,3–5).…”

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confidence: 99%

Physiology of the Aging Kidney

Delanaye

Pottel

Melsom

2022

CJASN

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Senescence could be defined as the gradual deterioration of functional characteristics in living organisms. The word senescence can refer to either cellular senescence or to senescence of the whole organism. Kidney senescence has been well described at the cellular and microscopic levels, with a distinction between the microstructural changes observed in normal physiologic aging versus in diseases (1,2). The effect of kidney senescence on GFR has been relatively well described but mainly from cross-sectional data, which are not ideal from a methodologic point of view (1,(3)(4)(5). After a period of kidney maturation in the first years of life, GFR remains constant until around 40 years. From the fourth decade, GFR is declining in line with the loss of nephrons (1). However, several important questions are still open. Is this decline observed in everyone? Is this physiologic decrease in GFR the same in men and women? Is this decline in GFR linear? Also, the evolution of GFR at the extremes of life is, by nature, difficult to study. Recently, Smeets et al.(6) assembled cross-sectional data from the literature to describe the evolution of GFR during the first 5 days after birth. On the other side of the age curve, data on GFR evolution in the elderly are scarce. Ideally, GFR slopes should be studied with longitudinal data using the measured GFR (exogenous clearance methods), but this is very challenging.In this issue of CJASN, Schaeffner et al. ( 7) studied the course of GFR with age in a longitudinal study of 2069 community-dwelling older persons (mean age of 8067 years old; the Berlin Initiative Study [BIS]) with eGFR and a follow-up time of 6.1 years. Study participants were members of the largest German statutory health insurance living in Berlin. The response rate in the BIS cohort has been reported to be relatively low (8%), but the loss to follow-up and the number of missing data were low in this study. The goal of the authors was double: "describe the crude and adjusted age-related course of eGFR in a population of individuals aged $70" and "define reference values for both sexes" (7). In our opinion, the population studied does not allow the authors to really "define" reference values. Indeed, although large and population based, their population may not be representative of the global German population over 70 years (and the authors never claimed such representativeness). Also, their population is obviously not a healthy one (e.g.,

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confidence: 99%

Physiology of the Aging Kidney

Delanaye

Pottel

Melsom

2022

CJASN

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“…Recent studies give much support to the notion that the absence of age-adapted thresholds of GFR for defining CKD leads to overdiagnosis of this condition in older adults [42 && ,43 && ,58,59]. To be sure, the processes involved in the generation of CKD and kidney aging share many elements in common [60]. CKD may accelerate the processes involved in healthy aging and vice-versa, however, disentangling the cause-and-effect aspects can be very difficult [61].…”

Section: The Inter-relationships Of Kidney Aging and Chronic Kidney D...mentioning

confidence: 99%

“…To be sure, the processes involved in the generation of CKD and kidney aging share many elements in common [60]. CKD may accelerate the processes involved in healthy aging and vice-versa, however, disentangling the cause-and-effect aspects can be very difficult [61].…”

Section: The Inter-relationships Of Kidney Aging and Chronic Kidney D...mentioning

confidence: 99%

Healthy and unhealthy aging on kidney structure and function: human studies

Đenić

Rule

Glassock

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewThis review is intended to provide an up-to-date analysis of the structural and functional alterations of the kidneys that accompany healthy and unhealthy aging in humans. Macro-and micro-structural changes and glomerular filtration rate (whole kidney and single nephron) accompanying aging will be stressed. Recent findingsComparative findings concerning distribution of anatomic changes of the kidney healthy and unhealthy aging are reviewed. Challenges concerning definition of chronic kidney disease (CKD) in otherwise healthy aging patients are discussed. The complex interactions of CKD and aging are discussed. The role of podocyte dysbiosis in kidney aging is reviewed. SummaryKidney aging is a complex phenomenon often difficult to distinguish from CKD. Nonetheless, phenotypes of healthy and unhealthy aging are evident. Much more information concerning the molecular characteristics of normal kidney aging and its relevance to chronic kidney disease is needed.

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“…However, younger individuals (aged <40 years) tend to have mean eGFRs of more than 100 mL/min/1.73m 2 , and would lose a large amount of kidney function before being diagnosed with chronic kidney disease using this fixed eGFR threshold 910. The effect of age on eGFR and clinical risk is uncertain, specifically at higher levels of eGFR (60-100 mL/min/1.73m 2 ) 291112131415. This gap in knowledge has resulted in limited guidance on how best to manage and potentially mitigate risk of loss of kidney function in younger adults with an early, reduced eGFR.…”

Section: Introductionmentioning

confidence: 99%

Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study

Hussain

Grubic

Akbari

et al. 2023

BMJ

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Objective To study age specific associations of modest reductions in estimated glomerular filtration rate (eGFR) with adverse outcomes. Design Retrospective, population based cohort study. Setting Linked healthcare administrative datasets in Ontario, Canada. Participants Adult residents (18-65 years) with at least one outpatient eGFR value (categorized in 10 unit increments from 50 mL/min/1.73m 2 to >120 mL/min/1.73m 2 ), with no history of kidney disease. Main outcome measures eGFRs and hazard ratios of composite adverse outcome (all cause mortality, any cardiovascular event, and kidney failure) stratified by age (18-39 years, 40-49 years, and 50-65 years), and relative to age specific eGFR referents (100-110 mL/min/1.73m 2 ) for ages 18-39 years, 90-100 for 40-49 years, 80-90 for 50-65 years). Results From 1 January 2008 to 31 March 2021, among 8 703 871 adults (mean age 41.3 (standard deviation 13.6) years; mean index eGFR 104.2 mL/min/1.73m 2 (standard deviation 16.1); median follow-up 9.2 years (interquartile range 5.7-11.4)), modestly reduced eGFR measurements specific to age were recorded in 18.0% of those aged 18-39, 18.8% in those aged 40-49, and 17.0% in those aged 50-65. In comparison with age specific referents, adverse outcomes were consistently higher by hazard ratio and incidence for ages 18-39 compared with older groups across all eGFR categories. For modest reductions (eGFR 70-80 mL/min/1.73m 2 ), the hazard ratio for ages 18-39 years was 1.42 (95% confidence interval 1.35 to 1.49), 4.39 per 1000 person years; for ages 40-49 years was 1.13 (1.10 to 1.16), 9.61 per 1000 person years; and for ages 50-65 years was 1.08 (1.07 to 1.09), 23.4 per 1000 person years. Results persisted for each individual outcome and in many sensitivity analyses. Conclusions Modest eGFR reductions were consistently associated with higher rates of adverse outcomes. Higher relative hazards were most prominent and occurred as early as eGFR <80 mL/min/1.73m 2 in younger adults, compared with older groups. These findings suggest a role for more frequent monitoring of kidney function in younger adults to identify individuals at risk to prevent chronic kidney disease and its complications.

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The Kidney in Normal Aging

Cited by 25 publications

References 11 publications

Physiology of the Aging Kidney

Physiology of the Aging Kidney

Healthy and unhealthy aging on kidney structure and function: human studies

Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study

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