This term is used to denote thickening of the wall of the artery associated with narrowing of the vascular lumen leading to increased wall/radius ratio [5].

Thickening of the arterial wall can be produced by different morphologic processes which include hyperplasia and/or hypertrophy of the medial vascular smooth muscles, fibrosis of the media, and/or fibrosis of the intima [6]. These lesions have been reported in hypertension, diabetes mellitus, and aging and increase in frequency with advancing age [5, 6].

Intimal fibrosis, also known as intimal fibroplasia, is the more specific lesion of the aging renal microvasculature [5, 6]. It involves small and larger interlobular arteries with a diameter of 80–300 μm. It is characterized by progressive thickening of the intima by reduplication of the elastic tissue and atrophy of the underlying media associated with loss of vascular smooth muscle cells [5, 6]. The media may even disappear almost completely when intimal thickening becomes maximal [17]. In contrast, in the very small interlobular arteries which give rise to the afferent arterioles, the intima becomes thicker by subendothelial deposition of hyaline and collagen [12].

Intimal fibroplasia which renders the vessel wall rigid is a universal finding in kidneys of elderly subjects [5, 6, 8]. Although it starts early in life, it becomes much more prominent after the age of 50 years [5, 6, 8].

Intimal fibroplasia is not limited to the renal vasculature but involves other organs such as the liver, the spleen, and the adrenal gland [8].

The etiology of intimal fibroplasia remains elusive. It may be enhanced or even precipitated by blood pressure elevation and hypertension [5, 6, 8]. It appears to be associated with global glomerulosclerosis rather than by hyaline arteriosclerosis and subsequent subcapsular injury [5, 6].

Arteriolar hyalinization, also known as hyaline arteriolosclerosis, is another feature of the aging renal microvasculature [5, 6]. The frequent occurrence of hyaline arteriolosclerosis/arteriolar hyalinization with increasing age was first described by Moritz and Oldt. This lesion which involves mainly the 10–30 μm diameter afferent arterioles is characterized by deposition of hyaline, a term derived from the Greek word “hyalos,” which is a glassy eosinophilic homogeneous material [18, 19]. Ultrastructurally, hyaline deposition is associated with (1) the presence of a homogeneous material which, by immunofluorescence, contains plasma proteins, (2) thinning of the media and atrophy of vascular smooth muscle cells, and (3) irregular thickening of the basement membrane and collagen [19]. Hyaline change occurs patchily along the length of the afferent arteriole and is predominant in its proximal portion and rarely extends into the glomerular capillaries [18, 19]. Further, hyaline deposition is rare in the interlobular arteries and when present occurs in the orifice of the afferent arteriole [18].

Hill and Bariety examined the relationship between hyaline arteriolosclerosis and glomerular structure in aging humans. They identified three types of changes in the afferent arterioles, namely, no hyaline deposition, non-obstructing hyaline, and obstructing hyaline. These investigators reported that, compared to those without hyaline lesions, afferent arterioles with nonoccluding hyaline deposits had a much larger lumen, twice as great (480 ± 240 μm² vs 204 ± 160 μm²), with corresponding increases in diameter and outer circumference and a markedly reduced wall/lumen ratio (3.2 ± 1.8 vs 6.4 ± 6.1 %). In the areas involved by hyaline deposition, the wall thickness was thinner (7.4 ± 3.9 μm vs 15.9 ± 5.8 μm), and vascular smooth muscle cells were atrophic, which might impair the constricting capacity of the vessel [17].

The incidence and severity of hyaline afferent arteriolosclerosis is dependent on age and BP levels. In kidneys of normotensive subjects, Smith reported that minor degrees of sclerosis occur in the third to fourth decades, increasing gradually with age and becoming significant in the fifth to sixth decades [19] although these vascular changes remain minor [19]. However arteriolosclerosis increases as the blood pressure rises even with BP differences in the normal range. Arteriolosclerosis was found in 13.5 % of patients with systolic BP of 90–129 mmHg, in 22.1 % of those with BP of 130–139 mmHg, and in 34.1 % of those with BP above 140 mmHg [19]. Smith concluded that arteriolosclerosis of the afferent arteriole appears to be an age change that is enhanced by hypertension [19].

Arteriolar hyalinization involves also the efferent arterioles. However, in contrast to the afferent arterioles, subendothelial hyaline deposits on the efferent arterioles are scarce, occurring in only 7–9 % of kidneys of nondiabetic normotensive or hypertensive subjects [15, 16, 18]. They appear to be also age related, as they are not seen before the age of 40 years but increase in incidence with age [18]. They are independent of BP levels or presence of hypertension but are greatly enhanced by diabetes mellitus [18]. The hyaline deposits in the efferent arterioles occur patchily along the vascular wall and frequently surround and constrict the vascular lumen [18]. Although hyalinization of both afferent and efferent arterioles appears to be age related, they are greatly enhanced by diabetes mellitus [5, 6, 18].

An increased prevalence of other abnormalities in the renal vasculature has been reported. In postmortem angiographic studies in subjects beyond the seventh decade, tapering of interlobular arteries and increased tortuosity of intralobular arteries have been observed [20].

The number of glomeruli varies with age and gender [5, 6, 11, 27]. Several studies have documented a reduction in the number of glomeruli with aging in both human and experimental animals [5, 6, 8, 9]. Using an accurate and unbiased stereologic method, Nyengaard and Bendsten demonstrated that the number of glomeruli in kidneys in subjects coming to autopsy declines with age [27]. Subjects younger than 55 years had a greater number of glomeruli per kidney than those older than those of 55 years, 695 × 10³ versus 560 × 10³, respectively [27]. The reduction in the number of nephrons is thought to result from both glomerulosclerosis and resorption of obsolescent glomeruli [27].

In the senescent kidney, glomerular lobulations tend to disappear, and the length of the glomerular tuft perimeter decreases [28, 29]. Accordingly, these morphologic changes, associated with loss of nephrons, contribute to the observed age-related reduction in surface area available for filtration and reduction in glomerular filtration rate [28, 29].

Sclerosis of the glomerulus is defined as acellular obliteration of the glomerular tufts leading to complete solidification of the glomerulus [5, 6]. This process is referred to as global glomerulosclerosis.

The incidence of sclerotic glomeruli rises with advancing age from less than 5 % at ages 40–45 years to 10–30 % of the total glomerular population by the eighth decade [5, 6, 8, 30].

The pattern of glomerular and vascular changes differs according to the renal zones. In the juxtamedullary glomeruli, the sclerosing damage in aging subjects results in a vascular connection between the afferent and efferent arterioles which, by shunting blood past the obsolescent glomeruli, maintains an adequate rate of medullary blood flow [30–34]. In contrast, in the cortex, global glomerulosclerosis is associated with obliteration of the arteriolar blood supply, eventually leading to resorption of the obsolescent sclerosed glomeruli [30–34].

There is some controversy as to the pathogenesis of glomerulosclerosis. In some studies, glomerulosclerosis and the associated tubulointerstitial changes are attributed to both intimal fibroplasia and hyaline arteriolosclerosis, while in others, the renal parenchymal changes appear to correlate better with intimal fibroplasia [15, 30].

The number of sclerosed glomeruli is linked to age and microvascular renal pathology [30]. However, age-related glomerular involution may occur independently of events in the renal microvasculature [30].

Totally sclerosed glomeruli are more frequent in aged men than in aged women [30–35].

With the evolution of senescence, the number of remnant intact (nonsclerotic) glomeruli decreases with age while their size enlarges [30]. The enlarged (intact) glomeruli display specific morphologic features. They have increased tuft size, dilated hilar capillaries, increased mean area of individual capillaries, and increased total capillary area [17, 36]. They are served by markedly dilated afferent arterioles with non-obstructing luminal hyaline deposits [17, 36]. These morphologic features predispose glomeruli to hemodynamic and physical injury leading to global glomerulosclerosis [17, 30, 36].

There is, however, no unanimity as to the zonal distribution of enlarged glomeruli. Newbold et al. measured single cross-sectional areas of outer cortical and juxtamedullary glomeruli in 41 adults aged 22–92 years with a mean age of 61 year and reported that glomerulosclerosis was more severe in the outer cortex, while the juxtamedullary glomeruli had a significant greater glomerular area, and the enlargement of the juxtamedullary glomeruli was positively correlated with cortical glomerulosclerosis [33]. The authors postulated that the increased number of sclerotic glomeruli (glomerulosclerosis) in the superficial cortex shifts glomerular blood flow to the remnant nonsclerotic juxtamedullary nephrons leading to glomerular hypertension, hyperfiltration, and increased risk of glomerulosclerosis [33]. In contrast Samuel et al. using the dissector (Cavalieri method) to estimate the distribution and volumes of glomeruli in the superficial, middle, and juxtamedullary cortex in autopsy kidneys in 12 young male adults aged 20–30 years and 12 older males aged 51–69 years found that glomerular mean volume was 20 % larger in the superficial cortex than in juxtamedullary zone [34]. Global glomerulosclerosis was also more severe in the superficial cortex. In kidneys of young adults, there were no significant differences between superficial and juxtamedullary glomeruli [34].

In a recent study, Hoang et al. evaluated the extent and mechanisms of age-related reduction in glomerular filtration rate (GFR) in healthy aging volunteers and in healthy transplant kidney donors [37]. The study included 159 healthy volunteers aged 18–88 years and 33 healthy transplant kidney donors aged 23–69 years. Glomerular dynamics were evaluated in the 159 healthy volunteers, while renal biopsy from 33 healthy kidney transplant donors was subjected to a morphometric analysis to determine glomerular hydraulic permeability and filtration surface area [37].

In their study, Hoang et al. reported that, compared to the healthy younger subjects, healthy elderly volunteers had a 22 % lower GFR (81 ± 17 vs 104 ± 15 ml/min/1.73 m²) and a 28 % lower renal plasma flow (RPF) (413 ± 106 vs 576 ± 127 ml/min/1.73 m²). Further, the computed Kf (two-kidney ultrafiltration coefficient) was significantly reduced below youthful levels by 21–53 % [37]. Morphometric studies in renal biopsy specimens from healthy kidney transplant donors revealed reduced filtration surface density (0.1 ± 0.01 vs 0.13 ± 0.04 μm³/μm³) and epithelial filtration slits (1,110 ± 17 vs 1,272 ± 182 slits/mm) and increased glomerular basement membrane thickness (461 ± 81 vs 417 ± 61 mm). According to these investigators, this study indicates that the intrinsic hydraulic permeability is reduced in aging individual glomeruli, which contributes to the age-related renal functional impairment [37]. Thus, an overall reduction in the number of functioning glomeruli, increased glomerular base membrane thickness, and accumulation of mesangial matrix limit both glomerular filtration area and glomerular permeability [37].

An increased frequency of direct continuity between afferent and efferent arterioles is a prominent feature of aged kidneys [5, 6, 30]. In the juxtamedullary glomeruli, glomerular sclerosis is associated with formation of a direct channel between afferent and efferent arterioles, referred to as arteriolae rectae verae or aglomerular arterioles which maintain blood flow in juxtamedullary nephrons. In the cortex, a different pattern of change predominates. Degeneration of glomeruli results in atrophy of the afferent and efferent arterioles. This leads to a gradual reduction in blood flow in cortical nephrons and eventual global sclerosis [30].