Tick-Tock Chimes the Kidney Clock – from Biology of Renal Ageing to Clinical Applications

Rowland, Joshua; Akbarov, Artur; Maan, Akhlaq Ahmed; Eales, James; Dormer, John; Tomaszewski, Maciej

doi:10.1159/000486907

Cited by 14 publications

(12 citation statements)

References 80 publications

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“…After 50 years of age, the eGFR declines about 1.15 and 1.45 mL/min per 1.73 m 2 per year after 70 years of age [15,16]. This GFR decline is highly variable among individuals [17]. Therefore, some nephrologists claim that the GFR decline with age may be preventable [18], whereas others claim that it is a physiological process, and therefore, the criteria for diagnosis of CKD in aged adults has to be revised [19,20].…”

Section: Is Kidney Aging a "Treatable" Condition?mentioning

confidence: 99%

Phosphate and Kidney Healthy Aging

Rubio‐Aliaga

2020

Kidney Blood Press Res

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Background: The aging population is increasing rapidly, much faster than our understanding on how to promote healthy aging free of multimorbidities. The aging kidney shows a decline in its function. Whether this decline is preventable or physiological is still debated. Main risks factors for developing CKD are aging common comorbidites, such as hypertension, diabetes, and obesity. Phosphate is vital for our organism, but it is also present in a great variety of food products as food additive and preservative. Due to the higher consumption of processed food in the last century, concern has arisen if a chronic high consumption of phosphate may be toxic impacting on healthy aging. Summary: Several studies show an association between higher serum phosphate levels and a higher risk of overall mortality and cardiovascular disease. Moreover, higher phosphate levels also worsen CKD progression and may contribute to renal dysfunction in healthy individuals. Acute high phosphate intake is rare but can cause acute kidney injury. Yet, the question if controlling phosphate intake may modulate serum phosphate concentrations remains unanswered, as assessment of phosphate intake is still a difficult task. Phosphate consumption estimations by dietary recalls are largely underestimated, especially in populations groups consuming high amount of processed food. Key Message: A healthy diet with phosphate source from food may contribute to promote healthy aging and longevity.

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Section: Is Kidney Aging a "Treatable" Condition?mentioning

confidence: 99%

Phosphate and Kidney Healthy Aging

Rubio‐Aliaga

2020

Kidney Blood Press Res

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“…Aging is associated with a decline in health and integrity of the human kidney 1 . Indeed, from the fourth decade of life, the glomerular filtration rate falls by 8 ml/min per 1.73 m 2 every 10 years 2 .…”

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confidence: 99%

Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics

Rowland

Akbarov

Eales

et al. 2019

Kidney International

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Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype–Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1 , PPP1R3C , LTF and TSPYL5 , correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.

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“…Given that the presence of GS > 10% in >85% KDPI kidneys had no significant impact on delayed graft function rate, acute rejection, or patient survival, the underlying explanation for higher graft failure in GS > 10% kidneys is likely due to the progressive kidney aging process in a kidney with less residual function. As the phenotype of GS is associated with podocyte detachment and a reduced number of functioning and viable glomeruli, this leads to increasing ESKD prevalence [36,37]. It has been estimated that an allocation strategy based on pretransplant donor biopsy would increase the incidence of marginal KDPI (80% to 100%) renal transplants by over 20%, which would translate into an overall increase of 4% for the entire pool of donors [38].…”

Section: Discussionmentioning

confidence: 99%

Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes

Cheungpasitporn

Vaitla

Chewcharat

et al. 2020

JCM

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Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0–10%, 11–20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0–10% GS (58.0%), 11–20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0–10% GS, 68.9% in 11–20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0–10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11–20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0–10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

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Tick-Tock Chimes the Kidney Clock – from Biology of Renal Ageing to Clinical Applications

Cited by 14 publications

References 80 publications

Phosphate and Kidney Healthy Aging

Phosphate and Kidney Healthy Aging

Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics

Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes

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