The Kidney in Normal Aging

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

doi:10.2215/cjn.10580821

Cited by 18 publications

(11 citation statements)

References 11 publications

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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%

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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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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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“…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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“…Ageing is associated with a time-dependent decline of organ function, which is especially evident in the kidney with the appearance of histologic lesions, such as tubular atrophy, interstitial fibrosis, glomerulosclerosis, and arteriosclerosis. Kidney function progressively declines with age, due to structural changes that cause a reduction of functioning glomeruli and renal mass, podocyte dysfunction, and malfunction of mechanisms important in cellular repair 3 . Glomerular diseases are in turn more common and associated with worse outcomes in older patients 4 .…”

Section: Introductionmentioning

confidence: 99%

Age-Modulated Immuno-Metabolic Proteome Profiles of Deceased Donor Kidneys Predict 12-Month Posttransplant Outcome

Charles

Fawaz

Vaughan

et al. 2023

Preprint

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Organ availability limits kidney transplantation, the best treatment for end-stage kidney disease. Deceased donor acceptance criteria have been relaxed to include older donors with higher risk of inferior posttransplant outcomes. More granular prediction models, based on deeper resolution organ assessment and understanding of damage processes, could substantially improve donor organ allocation and reduce graft dysfunction risk. Here, we profiled pre-implantation kidney biopsy proteomes from 185 deceased donors by high-resolution mass spectrometry and used machine learning to integrate and model these data, and donor and recipient clinical metadata to predict outcome. Our analysis and orthogonal validation on an independent cohort revealed 136 proteins predictive of outcome, 124 proteins of which showed donor-age modulated predictive effects. Observed associations with inflammatory, catabolic, lipid metabolism and apoptotic pathways may predispose donor kidneys to suboptimal posttransplant outcomes. Our work shows that integrating kidney proteome information with clinical metadata enhances the resolution of donor kidney quality stratification, and the highlighted biological mechanisms open new research directions in developing interventions during donor management or preservation to improve kidney transplantation outcome.

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The Kidney in Normal Aging

Cited by 18 publications

References 11 publications

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

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

Age-Modulated Immuno-Metabolic Proteome Profiles of Deceased Donor Kidneys Predict 12-Month Posttransplant Outcome

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