What is ‘nephrosclerosis’? Lessons from the US, Japan, and Mexico

Richard E. Tracy, and Toshiharu Ishii1

Department of Pathology, Louisiana State University Medical Center, New Orleans, LA, USA and 1 Department of Pathology, Toho University School of Medicine, Ota-ku, Tokyo, Japan



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 
Background. Selected features of ‘nephrosclerosis’ can be quantitated morphometrically in renal histology at autopsy. Specimens are available from Japan, Mexico, and the US (blacks and whites).

Methods. Autopsies of men and women aged 15–79 years provided renal samples for paraffin sectioning. These were assembled in New Orleans for objective evaluation after standardized staining with PAS-Alcian blue and interspersion with each other. Obsolescence of glomeruli, interstitial fibrosis, fibroplastic intimal thickenings of arteries, and arteriolar hyalinization, as operationally defined, were measured by objective morphometry.

Results. Obsolescence of glomeruli and interstitial fibrosis displayed the expected correlation with arterial intimal fibroplasia, but failed to confirm any direct association with arteriolar hyalinization. Some of the variation of ‘nephrosclerosis‘, within and between populations, cannot be fully explained by microvascular defects.

Conclusions. Arterial intimal fibroplasia appeared to promote ‘nephrosclerosis’, in the sense of fibrous replacement of atrophied nephrons, but arteriolar hyalinization did not. Hyaline deposits in arterioles may offer little or no threat to the integrity of the affected nephrons. ‘Nephrosclerosis’ appears to be multifactorial; it may be, in part, a consequence of fibroplasia in microscopic arteries causing ischaemic injury to scattered nephrons, but may also be a confluence of basically separate conditions, only some of which are known.

Keywords: aging; arteriolosclerosis; arteriosclerosis; human; hypertension



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 
The descriptive pathology of benign nephrosclerosis includes four diagnostic features that lend themselves to precise morphometry in paraffin sections, obsolescence of glomeruli, interstitial fibrosis, arterial intimal fibroplasia, and arteriolar hyalinization. The gathering together under one name, nephrosclerosis, implies that the four histologic features are all diagnostic elements of a single disease entity [1]. Recent evidence, however, has raised some doubts about such close linkages. These four features seem at times to act independently of each other across the groupings of age, race, sex, cause of death, and geographic region [25]. ‘Nephrosclerosis’, when precisely defined by objective morphometry, may not be a single disease entity in the sense of responding to a single aetiology such as hypertension or aging. Rather, it might often be a mixture of several separate conditions, which jointly converge upon a state of poor health.

A novel approach to these matters is explored here making use of a collection of specimens already assembled for another purpose [4]. In that study, the fibroplastic and the hyaline forms of vasculopathy, quantified separately, were compared with blood pressure levels obtained by community surveys in Japan and the US. The study found blood pressure to parallel fibroplastic but not hyaline vasculopathy, because hyalinization was discordantly low in autopsy samples from Japan. This report now considers a related question: does ‘nephrosclerosis’, assessed in tissue sections at autopsy as fibrous replacement of atrophied nephrons, relate equally well to fibroplastic and hyaline forms of vasculopathy, or does it relate predominantly to one or the other form? Previous studies [1,6,7] did not quantify the pathological variables or separate the hyaline from the fibroplastic forms of vasculopathy; these refinements are introduced here for the first time.

The approach taken here is to define nephrosclerosis precisely in terms of threshold values for objectively measured interstitial fibrosis and glomerular obsolescence. The condition thus defined is then related statistically to the two forms of vasculopathy, also measured objectively, with extension of the relationships across geographic boundaries.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 
Selection of cases
(i) The Toho University School of Medicine supplied renal tissues from 270 autopsies. These tissues were from men and women of ages 15–92 years who died from assorted causes, mostly cancers, during 1986–1987 or from 1995 to 1996. A basal group was constructed by excluding instances of cardiovascular disease (CVD, 15 cases) and chronic renal diseases (15 cases), retaining 240 cases. (ii) The Orleans Parish Coroner's Office supplied renal tissues from 424 autopsies. Tissues were from men and women of ages 15–102 years dying of assorted causes, mostly violent, during 1992–1997. A basal group retained 339 cases, excluding 15 cases of chronic renal disease, and 15 cases of CVD. (iii) The Forensic Medical Service of Mexico City supplied renal tissue from 111 autopsies. These tissues were from men of ages 15–64 years who died as a result of violence during 1986–1987; no instance of specific renal disorder was encountered in the tissue sections. Further details of these collections of specimens are available elsewhere [3,4,8]. These three cities were originally selected to compare atherosclerosis in aortas and coronary arteries, and opportunistically also provided renal samples. The findings reported here were unexpected, and not intentionally sought by predesignated selection of cities.

Basal cause of death group
Subjects that died from violent or natural causes who had no known relationship to hypertension comprise the basal group. The basal group offers a sample of the population that is approximately representative of its hypertensive prevalence [9].

Processing of renal tissues
Samples of kidney tissue were prepared as in routine autopsies. Blocks of tissue cut perpendicular to the capsular surface were fixed and stored in acetate-buffered 10% formaldehyde. Samples embedded in paraffin were sectioned at 6 µm, and stained with periodic acid Schiff-Alcian blue. Generally, a total area of renal cortex of 2–4 cm2 was represented in one or two sections. Specimens from Japan and Mexico were embedded in paraffin for transport to New Orleans, where staining and morphometry were carried out.

Morphometry of vasculopathies
Arteries in tissue sections were examined systematically under the x10 objective lens by previously reported techniques [2,5]. The outer diameter of the least axis of the elliptic profile was measured under the x10 objective lens, excluding the adventitia, and measured from one outer media to the other. The thickness of intima was measured under the x40 lens. Intimal thickness was expressed as a percentage of outer diameter, %OD (Figure 1DGo), averaged over all readings within the size range of 150–300 µm OD, referred to as Rc. These arteries are believed to serve chiefly a conduit function. A similar measure averaged for vessels of 80–150 µm OD is referred to as Rr. These smaller arteries are thought to provide a significant resistance function. An average of these two measures, Ra, is used in the analyses reported here. All hyalinized vessels in the section were counted (Figures 1AGo and 2Go), and the number divided by the area of renal cortex. The ratio is expressed as the square root to reduce the severe skewness in the frequency distribution of counts of hyalinized arterioles, {surd}(N/cm2). Areas of inflammation or discrete scar were omitted because these can introduce severe arterial abnormalities that are not generally representative of the specimen as a whole.



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Fig. 1. (A) Hyaline deposits (arrows) in an afferent arteriole serving an intact glomerulus. (B) An obsolete glomerulus served by an intact arteriole. (C) Arteriole emerging from a fibroplastic interlobular artery is widely patent; it has arteriolar features within the intimal compartment of the parent vessel (curved arrow). (D) As in (C), but with an artefactual stricture on the emerging arteriole; the arteriole takes on a hyaline deposit after emerging (straight arrow). Measurements determine R=100(T+S)/2OD, using outer diameter (OD) and the average of two intimal thicknesses, (T+S)/2. Media is withered or absent at the ends of the OD line. PAS, bar=50 µm.

 


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Fig. 2. Abundant hyaline deposits in arterioles and terminal arteries (arrows) are accompanied by the absence of obsolete glomeruli or interstitial fibrosis. This is case ‘a’ in Figure 5Go. PAS, x120.

 



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Fig. 5. Each symbol represents an autopsy of a subject of age >44 years in New Orleans or Tokyo. Symbols a and b identify cases illustrated in Figures 2Go and 3Go, respectively. The solid oblique line depicts equation 3, which optimally separates open symbols from spots; the dashed oblique line represents equation 4 using definition II for ‘nephrosclerosis’.

 
The definition of ‘nephrosclerosis’
Obsolete glomeruli (Figure 1BGo) were counted under the x10 objective lens, and the area of examined tissue measured on a projector image [2]. The ratio of counts (C) to area (A) was transformed into percent of glomeruli: G=100(C/A)/160, after determining in a sample of specimens that each cm2 of renal cortex exhibits an average of 160 glomerular profiles. Although other reports [7,1013] construct a denominator for obsolete glomeruli by counting total glomerular numbers, no advantage is known for this operation in preference for the much more simple measurement of tissue section area. Tubular atrophy might sometimes increase glomerular proximity to raise C, but resorption of obsolete glomeruli will diminish C, and no study has been done to assess the net impact of these countervailing trends. The factor of 160 in the denominator used here is a unit conversion device to make the values of G roughly comparable to those reported in other studies. The arcsine transform sometimes recommended [10,13] was tested, but abandoned after little advantage was found in this particular application. Interstitial fibrosis was graded on a 5-point scale of severity, where 1 is 0–10% of the cortex affected; and grades 2, 3, 4, and 5 represent 11–30, 31–50, 51–70, and >70% of cortex affected, respectively [2]. These were assessed in all available low-power fields, and the average recorded. The use of point counting to determine interstitial tissue [1416] is important in needle biopsy materials, but has little to recommend it in autopsy materials, which offer large quantities of tissue for assessment. The features of chronic pyelonephritis were taken to be lymphocytic infiltration, thyroidization, periglomerular fibrosis, transcapsular fixation, and pelvic inflammation. Cases diagnosed with chronic pyelonephritis were discarded; six such cases were encountered. However, in practice, these features were often seen as scattered small islands and were nearly always present to some degree with interstitial fibrosis of grade 2 or greater, appearing to worsen with increasing arterial fibroplasia. No reliable way has yet been developed to objectively quantify these five features of pyelonephritis [1]. Biases can be introduced by exclusion or inclusion of these zones. If included, then an inflammatory process, pyelonephritis, will sometimes exaggerate our estimates of ‘nephrosclerosis’. If excluded, then some scars of non-inflammatory origin are sometimes omitted, thus biasing downward our estimate of ‘nephrosclerosis’. It was elected to avoid the first source of bias by omitting these features from consideration, excluding the affected areas from morphometry. The resulting downward bias is uniformly applied to all specimens and should have little effect on their relative rankings. ‘Nephrosclerosis’ (Figure 3Go) was categorized in three ways: (i) a mild form has interstitial fibrosis affecting >=11% of the specimen and obsolescence affecting >=3% of the glomeruli; (ii) a moderate form has fibrosis >30% and G>5%; and (iii) a severe form has fibrosis >50% and G>5%. Type I ‘nephrosclerosis’ comprises the mild or greater degrees, and type II comprises the moderate or greater degrees. These cutoff points are entirely arbitrary, and have no intrinsic superiority over other possible choices.



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Fig. 3. ‘Nephrosclerosis’, marked by fibrous replacement of atrophied nephrons, is accompanied by arterioles free of hyaline deposits (open arrows) and arteries with severe intimal fibroplasia. This case is ‘b’ in Figure 5Go. PAS, x120.

 

Description of variables
Table 1Go summarizes the foregoing list of the variables used in this report, together with descriptive information about them. The upper right triangle gives the raw product moment correlation coefficients, and the lower left triangle the age adjusted partial correlations. These statistics provide the information needed for multivariate analyses including correlation and regression.


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Table 1. Descriptive statistics for selected variables, including product moment correlation coefficients; 651 cases, total of three populations combined, excludes specific renal diseases

 

Discriminating ‘nephrosclerosis’
Subjects of ages 45–79 years were grouped into those with and without ‘nephrosclerosis’, morphometrically defined by numbers of obsolete glomeruli and extent of interstitial fibrosis. Data on vasculopathies were then used to predict the diagnosis of nephrosclerosis, using discriminant function analysis. Using definition I (mild or greater), the following discriminant functions were determined, (equation 1 for a pool of all New Orleans cases and equation 2 for Tokyo; these omit 30 instances of specific renal diseases of which six were examples of chronic pyelonephritis):

(1)

(2)
W gives the weighted average of Ra and Hy, which optimally separates subjects; when W>0, the subject is predicted to have ‘nephrosclerosis’ by definition I, when W<0, the subject is predicted to lack ‘nephrosclerosis’, with the predictions based solely upon objective assessment of microvasculature. Age and sex are rejected as not of added statistical significance; coefficients for Hy are not significant at P<0.05, but are retained to help emphasize the absence of any strong positive contribution of Hy to the weighted average, W. Standardized coefficients are given, so that the units of measure for W, Ra, and Hy are standard deviation units of the respective variables. T2 specifies the distance between mean W in subjects with and without ‘nephrosclerosis’ (definition I), and is measured in units of the squared standard deviation of W. % is the percentage of cases correctly classified as having or lacking ‘nephrosclerosis’ (objectively defined) using the information on vasculopathies as described by the equation. The standardized coefficients can be converted back to raw units of measure by dividing each coefficient by its appropriate standard deviation in Table 1Go. When doing this, the constant term c must be added. A version of these equations determined for the pool of all cases from both cities is plotted in a later graph as a solid diagonal line; another version, similarly determined using definition II of nephrosclerosis is also plotted as a broken line in the same graph (see Figure 5Go). Those plotted equations are given here in raw units of measure:

(3)

(4)



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 
Interstitial fibrosis and obsolete glomeruli tended to rise progressively with age in basal men of four populations and basal women of three populations (Table 2Go). The percentages of cases classed as having ‘nephrosclerosis’ increased with age in close parallel with the fibroplastic vasculopathy (Figure 4Go, left panel), but not with the hyaline form (Figure 4Go, right panel).


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Table 2. Mean values for obsolete glomeruli and interstitial fibrosis in men of four populations and women of three populations, by 10-year age groups; basal cases only

 


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Fig. 4. Numerous obsolete glomeruli accompanied by fibrous replacement of >=11% of the renal substance implies ‘nephrosclerosis’ by definition I (i.e. mild or greater degrees). The percentage of cases assigned to this category is plotted against mean values of fibroplastic and hyaline renovasculopathy for 10-year age groups in each population. Age groups increase from lower left to upper right in this diagram (15–24, 25–34, 35–44, 45–54, 55–64, and 65+ years at the angles of each of the lines).

 


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Table 3. Means of selected variables by sex group for three populations, age adjusted to mean age 45.4 years by regression; basal cases only

 

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Table 4. Means of selected variables for basal men of ages <55 years, in four populations

 



   Fibrous replacement of atrophied nephrons in four populations
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 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 
The four populations disclosed no simple pattern of rankings in Table 2Go. For instance, men from Tokyo had equal or greater degrees of interstitial fibrosis than the men in the other three populations in 16/17 comparisons within age groups, and an equal or greater extent of obsolete glomeruli in 14/17 comparisons. Women from Tokyo, however, equalled or exceeded the other two populations for only interstitial fibrosis (12/12 comparisons) but reversed this pattern for obsolete glomeruli (0/12 comparisons). Men from Mexico had equal or greater interstitial fibrosis than the New Orleans blacks or whites in 10/10 comparisons, but reversed this pattern for obsolete glomeruli. New Orleans blacks did not differ consistently or greatly from New Orleans whites in either of these observed quantities.

Renovasculopathies in four populations
Hyalinization of arterioles (renohyaline) was lowest in the Tokyo samples. This was seen in men and women including the full range of ages in three populations (Table 3Go), and in the men of limited age range in four populations (Table 4Go). Arterial intimal fibroplasia (renofibroplasia) was lowest in the Mexico samples, although not significantly different in comparison with Tokyo (Table 4Go). Renofibroplasia was moderately lower in men and women from Tokyo than from New Orleans, significantly so for blacks but not for whites (Tables 3Go and 4Go).

Relationship of obsolete glomeruli to fibroplastic and hyaline renovasculopathies at ages >44 years
Obsolete glomeruli tended to increase together with fibroplastic renovasculopathy, but not with arteriolar hyalin (Table 5Go). Glomeruli were 8.8% obsolete in the third of subjects with the highest renofibroplasia compared with 3.5% in the lowest third; this trend was similar at all degrees of renohyaline. Glomeruli were 5.7% obsolete in the highest compared with 5.1% in the lowest renohyaline group, an insignificant difference; similar lack of significance prevailed at all degrees of renofibroplasia.


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Table 5. Mean extent of obsolete glomeruli (percent of glomeruli) cross tabulated by fibroplastic and hyaline types of renovasculopathy; all cases age >44 years lacking specific renal disorders, age adjusted to mean age 61.1 years by regression

 

Relationship of interstitial fibrosis to fibroplastic and hyaline renovasculopathies at ages >44 years
Interstitial fibrosis tended to increase together with severe arterial fibroplasia, but not with arteriolar hyalin (Table 6Go). The third of subjects with the highest fibroplastic renovasculopathy averaged fibrosis grade 1.9 compared with 1.3 for the lowest third; this trend was similar at all degrees of renohyaline. The third of subjects with the highest degree of renohyaline averaged fibrosis grade 1.4 compared with 1.6 for the lowest third, an insignificant difference; this lack of significance was similar at all degrees of renofibroplasia. (Technical note: the grades of 1 and 2 were assigned to specimens with respectively 0–10 and 11–30% of the nephron mass replaced by interstitial fibrosis. Group averages were grade 1.3 and 1.9 respectively in the lowest and highest arterial fibroplasia classes, which correspond to ~9.5 and 18.5% fibrosis, Table 6Go.)


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Table 6. Mean extent of interstitial fibrosis (5-grade scale) cross tabulated by fibroplastic and hyaline types of renovasculopathy; all cases age >44 years lacking specific renal disorders, age adjusted to mean age 61.1 years by regression

 

Relationship of ‘nephrosclerosis’ to renovasculopathies in individuals of age >44 years
Cases with nephrosclerosis of ‘mild’ or ‘moderate’ degrees (definitions I or II) typically fall in the high range of renofibroplasia, but in the average range of renohyaline (open symbols shift rightward but not upward in Figure 5Go). The two oblique lines in the graph emphasize these relationships, because open symbols tend to be rightward and slightly downward from these lines. The solid line optimally separates the open symbols from the spots and represents equation 3, which uses definition I for ‘nephrosclerosis’. The broken line is determined using definition II (equation 4).



   Discussion
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 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 
The commonly used rubric ‘nephrosclerosis’ seems to imply a discrete disease entity, often thought to reflect hypertension as its sole aetiology. Yet, the diagnosis rests ultimately on assessment of histology in tissue sections obtained from biopsy or autopsy, and frequently lacks precision. The approach taken here is to define ‘nephrosclerosis’ objectively by attending exclusively to morphometric indicators for fibrous replacement of atrophied nephrons. The diagnosis is considered positive when interstitial fibrosis and/or glomerular obsolescence exceed certain arbitrarily imposed cutoff levels of severity. When defined in this way, instances of nephrosclerosis could be correctly predicted by assessment of microvasculature in ~70% of cases in this data set. The remaining 30% are presumably related to other processes such as tubular necrosis as in shock, interstitial nephritis, minor degrees of pyelonephritis, or other conditions.

Subjects with morphometrically defined ‘nephrosclerosis’ in this study often displayed the most severe intimal fibroplasia of interlobular renal arteries, but only average degrees of arteriolar hyalinization. These results are shown in Figure 5Go, where open symbols mostly sit rightward of the nearly vertical lines in the graph. Tokyo is similar to New Orleans in this regard, as seen by comparing equations 1 and 2. These findings identify fibroplasia in the interlobular arteries, but not hyalinization of arterioles, as potential contributors to ‘nephrosclerosis’.

Comparisons between populations generally reveal a better relationship of ‘nephrosclerosis’ to fibroplastic rather than hyaline vasculopathy (Figure 4Go). However, some discrepancies occur in the detailed comparisons. At the ages represented in the Mexican sample, 15–54 years (excluding two cases of ages 55–64 years), the Tokyo group shows the highest rankings for both glomerular obsolescence and interstitial fibrosis, even though fibroplastic vasculopathy is greater in the New Orleans sample, significantly so for blacks (Table 4Go). This pattern persists in the full sample of all ages, but only for interstitial fibrosis (Table 3Go). These findings suggest that the causes of ‘nephrosclerosis’ can be, at least to some degree, independent of vasculopathies across geographic boundaries. The Tokyo series of cases was assembled from hospital patients while those in Mexico and New Orleans were from forensic sources. Perhaps instances of shock or toxicity of medications might explain the aberrantly high level of ‘nephrosclerosis’ in the Tokyo group.

Most subjects with ‘nephrosclerosis’ did not display exceptional degrees of arteriolar hyalinization, even after the age of 44 years (Figure 5Go). This statistical outcome is in keeping with usual appearances in histologic sections. Hyalinized arterioles, when seen attached to glomeruli, typically serve intact glomeruli without evidence of ischaemic injury (Figures 1AGo and 2Go). Obsolete glomeruli are seldom presented in tissue sections in a plane to show the attached arterioles; when present, these arterioles nearly always lack hyaline deposits (Figures 1BGo and 3Go). Co-existence of an obsolete glomerulus with a hyalinized arteriole is a rarity to be found only by diligent search. Drawings made from serial sections by Smith [17] seem to show this result; the 138 hyalinized arterioles included in the drawings are all depicted as attached to intact glomeruli, while only three obsolete glomeruli are shown and they have intact arterioles. Katafuchi and Takabayashi [18] reached the same conclusion from inspection of needle biopsies in hypertensive patients, ‘These data suggest that intimal thickening of the small arteries, and not hyaline change, leads to atrophy of the renal parenchyma. A possible explanation is that the hyaline change causes a less severe or no luminal occlusion of the arterioles.’ Allbutt [19] seems to adopt this view, attributing it to Ziegler, ‘... so far as I know, the first pathologist to recognize the arteriosclerotic kidney ... due primarily to sclerosis of the renal arteries with, usually but not necessarily, participation of the intimate renal ramifications also’.

The possibility arises that hyalinization of an arteriole does not ordinarily threaten the integrity of the nephron. Hyaline deposits frequently originate in youth, and evidently linger thereafter into old age, whether by endurance or by steady-state turnover [3,4,6,7]. Their apparent persistence throughout life argues that the hyaline deposits may do no harm, but may actually contribute something salutary to the affected nephrons. With ordinary immersion fixation, hyaline masses often tend toward a globular shape, as in Figure 1AGo, and seem to encroach upon the lumen. However, fixation by perfusion of pressurized formaldehyde into the renal artery (Figure 6Go) regularly deforms these globular masses into flattened or crescent shapes, and fully restores the arteriolar lumen. When inflated back into the more nearly natural position, the hyaline mass typically gives the impression of filling a bulge in the arteriolar wall where the absence of muscle cells has abolished the media, bringing endothelium into contact with adventitia (arrows in Figure 6Go). This filling of bulges seems to partially restore a straightened and smoothed lumen in an arteriole that is otherwise severely tortuous with uneven caliber. Perhaps these hyaline deposits serve in some way to rescue nephrons that would otherwise grow obsolete sooner.



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Fig. 6. Perfusion of 3% formaldehyde into the renal artery at 100 mmHg pressure yields appearances that contrast with immersion fixation in Figure 1AGo. Hyaline deposits are indicated by arrows. PAS, bar=100 µm.

 
The usual descriptions of ‘nephrosclerosis’ include severe degrees of both hyaline and fibroplastic vasculopathy, in conflict with the finding here that most cases have only minor degrees of hyalinized arterioles. These usual descriptions refer only to the upper right quadrant of Figure 5Go, omitting the more abundant cases in the lower right quadrant, as if a biased selection of cases has occurred. The source of such a selection bias could easily be traced to the causes of death that lead to autopsy. Subjects who happen to harbour severe degrees of the two substantially independent processes, hyalinization and fibroplasia, are doubly at risk of death from heart disease or stroke [3]. An autopsy series heavily weighted with CVD will therefore contain many subjects in the upper right quadrant of the chart, simply because they are patients at a particularly high risk of death and autopsy. If such a biased sampling of cases should occur, then it could generate a spurious correlation of hyalinization with nephrosclerosis because of the ‘lurking variable’, CVD [20].

Heptinstall [1] provides a thorough review of these topics, and emphasizes glomerular hyperperfusion and ischaemia as possible causes of nephron loss together with hypertension and its renovasculopathies. As a possible source of ischaemia, strictures are sometimes seen at the ostia of afferent arterioles (Figure 1DGo). Although such strictures are usually absent, even when post-mortem collapse has affected the vessels (Figure 1CGo), they might sporadically cause the progressive loss of nephrons. It is easy to imagine that such constrictions could occur in vivo, especially during hypotensive episodes, so that ischaemia might selectively amputate the most vulnerable of scattered nephrons, leaving them to be visualized as obsolete glomeruli in a background of replacement fibrosis.



   Conclusions
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 
The entity ‘nephrosclerosis’ is poorly defined. Efforts to delineate the condition by objective morphometry are few and of limited scope [1116]. Findings reported here derive from objective quantification of operationally defined features in renal histology. The results contain some surprises. For instance, the fibrous replacement of atrophied nephrons emerged with no direct relationship to arteriolar hyalinization in this body of data. These findings might help draw attention to this important and greatly neglected area of pathology.



   Notes
 
Correspondence and offprint requests to: Dr Richard E. Tracy, Department of Pathology, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, LA 70112, USA. Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Fibrous replacement of atrophied...
 Discussion
 Conclusions
 References
 

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Received for publication: 15. 2.00
Revision received 12. 4.00.