Distinguishing age-related from disease-related glomerulosclerosis on kidney biopsy: the Aging Kidney Anatomy study

Kremers, Walter K.; Denic, Aleksandar; Lieske, John C.; Alexander, Mariam P.; Kaushik, Vidhu; Elsherbiny, Hisham E.; Chakkera, Harini A.; Poggio, Emilio D.; Rule, Andrew D.

doi:10.1093/ndt/gfv072

Cited by 89 publications

(73 citation statements)

References 16 publications

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“…Using a multi-center sample of 2052 living kidney donors, reference limits (95 th percentiles) have now been defined for the expected number of GSG on a biopsy section as predicted by age and the total number of glomeruli present. 28 In addition to GSG, tubular atrophy, interstitial fibrosis and arteriosclerosis also increase with older age and can be combined to define a sclerosis score (Figure 1). If nephrosclerosis is considered as the presence of two or more of the four main aforementioned abnormalities, prevalence among the youngest living donors was only 2.7% but increased to 73% among the oldest living donors.…”

Section: A) Micro-anatomical Changesmentioning

confidence: 99%

Structural and Functional Changes With the Aging Kidney

Denic

Glassock

Rule

2016

Advances in Chronic Kidney Disease

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523

370

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Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The micro-anatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macro-anatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous renal cysts. Among carefully-screened healthy kidney donors, glomerular filtration rate declines at a rate of 6.3 ml/min/1.73m2 per decade. There is reason to be concerned that the elderly are being misdiagnosed with chronic kidney disease. Besides this expected kidney function decline, the lowest risk of mortality is at a glomerular filtration rate of ≥75 ml/min/1.73 m2 for age <55 years but at a lower glomerular filtration rate of 45-104 ml/min/1.73m2 for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less renal functional reserve when they do actually develop chronic kidney disease and they are also at higher risk for acute kidney injury.

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Section: A) Micro-anatomical Changesmentioning

confidence: 99%

Structural and Functional Changes With the Aging Kidney

Denic

Glassock

Rule

2016

Advances in Chronic Kidney Disease

Self Cite

523

370

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“…With aging, the kidney cortical volume decreases (in parallel with declining GFR), while the medullary volume increases offsetting to some extent the impact of reduced cortical volume on overall kidney volume [13]. Microscopically, kidney aging is characterized by nephrosclerosis: increasing focal and global (not segmental) glomerulosclerosis (FGGS), interstitial fibrosis/tubule atrophy and arteriolosclerosis [14]. The clinical importance of this glomerulosclerosis, in particular, may be different in ‘healthy' aging compared to disease-induced pathology [15].…”

Section: Changes In Gfr and Kidney Anatomy With Agingmentioning

confidence: 99%

“…In ‘healthy' aging, the rate of decline of GFR is not correlated with the extent of nephrosclerosis - a decline in GFR of about 0.63 ml/min/1.73 m 2 per year is seen regardless of the sclerosis score on renal biopsy in living donors at any age [16]. The density of nonsclerotic glomeruli decreases by 7% per decade, while the density of FGGS increases by 14% per decade [14]. These microscopic findings suggest that the decline in GFR seen with aging is a phenomenon related to a slowly progressive loss of nephrons from age 30 onward.…”

Section: Changes In Gfr and Kidney Anatomy With Agingmentioning

confidence: 99%

Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease

Glassock

Rule

2016

Nephron

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117

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The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD.

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“…Detailed anatomic and physiologic studies of the healthiest of the healthy, normal living donors for kidney transplantation by the Mayo Clinic and Cleveland Clinic have been particularly revealing. [14][15][16][17][18][19] We are all born with a complement of nephrons determined in large part by the process of nephrogenesis in utero. 20 This process can be influenced, either negatively or positively by the maternal-fetal nexus.…”

Section: What Is the Aging Kidney?mentioning

confidence: 99%