Visual Abstract
Abstract
Background Age, CKD risk factors, and kidney function are associated with larger glomerular volume and a higher percentage of globally sclerotic glomeruli. Knowledge of how these associations may differ by cortical depth is limited.
Methods To investigate glomerular volume and glomerulosclerosis across different depths of cortex, we studied wedge sections of the renal parenchyma from 812 patients who underwent a radical nephrectomy (for a tumor), separately characterizing glomeruli in the superficial (subcapsular), middle, and deep (juxtamedullary) regions. We compared the association of mean nonsclerotic glomerular volume and of glomerulosclerosis (measured as the percentage of globally sclerotic glomeruli) with age, obesity, diabetes, smoking, kidney function, and structural pathology in the superficial, middle, and deep regions.
Results The superficial, middle, and deep regions showed significant differences in glomerular volume (0.0025, 0.0031, and 0.0028 µm3, respectively) and in glomerulosclerosis (18%, 7%, and 11%, respectively). There was a marked increase in glomerulosclerosis with age in the superficial region, but larger glomerular volume was not associated with age at any cortical depth. Glomerulosclerosis associated more strongly with arteriosclerosis and ischemic-appearing glomeruli in the superficial region. Hypertension, lower eGFR, and interstitial fibrosis associated with glomerulosclerosis and glomerular volume to a similar extent at any depth. Diabetes and proteinuria more strongly associated with glomerulosclerosis in the deep and middle regions, respectively, but neither associated with glomerular volume differently by depth. Obesity associated more strongly with glomerular volume in the superficial cortex.
Conclusions Most clinical characteristic show similar associations with glomerulosclerosis and glomerulomegaly at different cortical depths. Exceptions include age-related glomerulosclerosis, which appears to be an ischemic process and is more predominant in the superficial region.
Histologic study of the kidney cortical parenchyma rarely considers depth. The use of percutaneous needle core biopsies facilitates the widespread use of kidney biopsies in clinical practice, but depth of the cortical parenchymal sample is often unclear. The presence of capsule or corticomedullary junction on the tissue specimen provides a partial indication of depth, but the amount of tissue that can be clearly identified as superficial (subcapsular) cortex or deep (juxtamedullary) cortex is usually limited, and many specimens lack capsule and/or corticomedullary junction. It is generally believed that there are two anatomically and functionally distinct nephron populations in the mammalian kidney. Superficial nephrons extend only into the outer medulla, whereas deep nephrons extend into the inner medulla and have larger efferent arterioles.1,2
Age and disease may localize to glomerular pathology at different depths. The two common, nonspecific glomerular pathologies are glomerulomegaly and glomerulosclerosis; both are associated with clinical characteristics and other structural pathology.3 Enlargement of glomeruli can lead to eventual collapse and glomerulosclerosis,4 and conversely, glomerulosclerosis can lead to compensatory enlargement of remaining glomeruli.5 In certain animal models, deep glomeruli are larger than superficial glomeruli,6−8 and glomeruli of intermediate depth.9,10 Several human autopsy studies of glomerular volume have also concluded that deep glomeruli are larger,11−13 although one study has found superficial glomeruli to be larger in older adults.14 Age-related glomerulosclerosis appears to occur predominantly in the superficial cortex.14,15 There is also evidence that age-related glomerulosclerosis leads to compensatory increase of glomerular volume in the deep cortex15 versus the superficial cortex.14 However, these autopsy studies have had small sample sizes and inherently lack clinical data to account for comorbidities and kidney diseases that are more common with age. Further, compensation for age-related glomerulosclerosis is not clearly evident in living humans as glomerular volume, single nephron GFR, and glomerular filtration capacity do not increase with healthy aging.16,17–19
To investigate the intricate relationship between glomerular volume and glomerulosclerosis across different depths of cortex in living humans, we studied wedge sections of the renal parenchyma in patients who underwent a radical nephrectomy. We had three objectives: to determine whether glomerular volume and its associated clinical characteristics differ by depth of cortex, to determine whether glomerulosclerosis and its associated clinical characteristics differ by depth of cortex, and to determine the association between glomerular pathology at different depths with other biopsy pathology.
Methods
Study Population
The study sample was an expansion of previously described patients that had undergone a radical nephrectomy for a renal tumor at Mayo Clinic Minnesota from 2000 to 2012.16 We only studied patients who underwent a complete unilateral nephrectomy for a renal tumor (usually renal cancer) with no metastatic lesions or positive lymph nodes at the time of surgery. Comorbidities do not generally exclude patients from radical nephrectomy unless severe enough to make the surgical risks outweigh the benefits of treating cancer. The study was approved by the Mayo Clinic Institutional Review Board.
Kidney Function and Risk Factors
The preoperative clinical evaluations of patients with renal tumor were reviewed to obtain height, body mass index (BMI), serum creatinine (corrected to standardized values if assayed prestandardization), 24-hour urine protein, hypertension status (as documented in medical record), and diabetes mellitus (as documented in medical record). The GFR was estimated using the creatinine-based CKD Epidemiology Collaboration equation.20 The 24-hour urine protein excretion was estimated from a spot urine protein-to-osmolality ratio.21 Three orthogonal linear dimensions on the preoperative computed tomography or magnetic resonance imaging scan were used to estimate renal tumor volume [volume=(1/6)π×a×b×c].22
Kidney Microstructure
The stored, formalin-fixed, whole kidney specimens were retrieved to obtain a large wedge section of parenchyma that was most distal to the tumor, which was then embedded in paraffin. A 3 µm thick section was cut from the paraffin-embedded tissue block, stained for periodic acid–Schiff, and scanned into high-resolution digital images (Aperio XT system scanner; Leica Microsystems, Inc., Buffalo Grove, IL; http:/www.aperio.com). Biopsy images were analyzed by investigators masked to age and other clinical characteristics to minimize bias. The scanned digital images were magnified with Image Scope software (Aperio version 12.2.2.5015 ) onto a large, touchscreen tablet. Regions were drawn at low magnification to define superficial cortex (the subcapsular strip of 3–4 glomerular diameters), the deep cortex (the juxtamedullary strip of 3–4 glomerular diameters),14,23,24 and the middle cortex (strip of 3–4 glomerular diameters halfway between superficial and deep cortical strips). Thick cortex had a thickness ≥6 mm and thin cortex had a thickness <6 mm. In thick cortex, two additional regions were identified, one halfway between the superficial and middle region (“superficial/middle”), and one halfway between the middle and deep region (“middle/deep”) (Figure 1). We could always get three depth regions in thin and five depth regions in thick wedge sections.
Representative wedge sections of thin and thick kidney cortex. (A) Thin cortex allowed measurements and quantification of glomeruli in three regions, superficial (glomeruli in red trace), middle (glomeruli in light green trace), and deep (glomeruli in blue trace). (B) Thick cortex allowed measurements and quantification of glomeruli in additional two regions, superficial/middle (glomeruli in dark green trace), and middle/deep (glomeruli in yellow trace). Black dashed lines in each biopsy section represent the two measurements of cortical thickness used to classify patients into thin versus thick cortex. Arcuate arteries are denoted with black arrowheads. Globally sclerotic glomeruli in all zones, in both panels were shown in pink trace.
At high magnification, glomerular cross-sectional profiles were traced and counted in each of the regions to calculate the mean nonsclerotic glomerular tuft volume (using the Weibel–Gomez stereological model)25 and the percentage globally sclerotic glomeruli (%GSG) for each region as previously described (Figure 1).5,16 The %GSG in each region was classified into four levels (0: <10%, 1: 10%–25%, 2: 26%–50%, and 3: >50%).26 Ischemic-appearing (but not sclerosed) glomeruli were identified by capsule thickening, pericapsular fibrosis, and a wrinkled (deflated) tuft.16 The percentage of nonsclerotic glomeruli that were ischemic-appearing (%ischemic glomeruli) was calculated for each region and dichotomized at ≤5% or >5%. The mean nonsclerotic glomerular volume (referred to as glomerular volume) was calculated using nonischemic and ischemic-appearing glomeruli. To remove the influence of smaller ischemic glomeruli, separate analyses were also performed using only nonischemic, nonsclerosed glomeruli (referred to as nonischemic glomerular volume).
Interstitial fibrosis/tubular atrophy (IF/TA) and arteriosclerosis were assessed for the entire cortex. To determine the percentage IF/TA, the total areas of IF/TA regions were divided by the total area of cortex (Supplemental Figure 1) and categorized as ≤10% or >10%, and as ≤25% or >25%.26 The average percentage luminal stenosis (from intimal thickening) was determined from the three most orthogonal small- to medium-sized arteries on the biopsy. The percentage luminal stenosis was determined from the area of intima divided by the area of intima and lumen and was dichotomized at ≤50% or >50% to define arteriosclerosis as previously described.3
Statistical Analyses
Cortical biopsy findings in superficial, middle, and deep regions were compared with a multivariate analysis of variance test for equal means (continuous variables), the Friedman test (ordinal variables), or Cochran Q test (binary variables). The glomerular volume, 24-hour urine protein, and tumor volume were log-transformed to normalize a right-skewed distribution. Linear regression was used to determine how glomerular volume associated with clinical characteristics. Linear regression with log-transformed %GSG would result in coefficients that corresponded to a percentage change of a percentage, which can be difficult to interpret. Instead, ordinal logistic regression was used to determine how %GSG category associated with clinical characteristics. Ordinal logistic regression with a four-category response variable (0–3) can be understood as three simultaneous binary logistic regressions comparing categories 0 versus 1–3, 0–1 versus 2–3, and 0–2 versus 3. The odds ratio associated with each predictor is assumed to be the same for each of these comparisons.
To test whether a given association was the same in all three regions, a chi-squared statistic was calculated on the basis of the normal joint distribution of the three coefficient estimates from the three regions. The chi-squared calculation required the variances and covariances of the coefficient estimates, and these were obtained from 1000 bootstrap samples. The null hypothesis of this “test for interaction” was that the true coefficients for the three regions were all equal. The models regressing glomerular volume or %GSG category on clinical characteristics were multivariable-adjusted for each other clinical characteristic. For the patients lacking a urine protein assessment, the mean 24-hour urine protein was used as an imputed value in multivariable analysis. Statistical analyses were performed using JMP version 13.0 (SAS Institute, Cary, NC; www.jmp.com) and R version 3.4.2 (R Core Team, R Foundation for Statistical Computing).
Results
Characteristics of Patients with Renal Tumor
We identified and obtained kidney wedge sections of 845 patients with a renal tumor. Ten patients were excluded for specific renal diseases on pathology: one each for amyloidosis, ESRD histology, severe chronic lymphocytic pyelonephritis, chronic interstitial nephritis, lymphomatous interstitial nephritis, crescentic GN, severe nodular glomerulosclerosis, FSGS with collapsing features, IgA nephropathy, and diffuse mesangial sclerosis with FSGS. Another 23 patients were excluded for missing clinical characteristics resulting in a sample size of 812 patients. Diabetic nephropathy occurred with mild to moderate diffuse mesangial expansion in 28 patients and nodular sclerosis in 12 patients; these were all included in glomerular volume and %GSG estimates. Segmental sclerosis occurred in 29 patients but was minimal when present; these were included in glomerular volume estimates. The demographic, clinical, and overall pathologic characteristics of the cohort are presented in Table 1. The median tumor volume was 100 cm3 (interquartile range, 37–249 cm3). The number of patients and numbers of nonsclerotic and globally sclerotic glomerular profiles in each of three cortical regions, per each decade of life, is presented in Supplemental Table 1.
Clinical characteristics and biopsy findings of patients with renal tumor
Differences in Glomeruli by Depth
The glomerular volume was largest in middle region, followed by the deep region, and superficial region (Table 2). Conversely the %GSG and percentage ischemic glomeruli were highest in superficial region, followed by deep region and middle region (Table 2). There were 406 biopsy sections with thick cortex (≥6 mm) and 386 biopsy sections with thin cortex (<6 mm) (Figure 1), whereas 20 biopsy sections had asymmetric thickness (Supplemental Figure 2). The glomerular volume and glomerulosclerosis patterns were compared between patients with thick versus thin cortex. Thick cortex was associated with larger glomerular volume than thin cortex in all three regions, but the pattern of middle largest and superficial smallest remained (Figure 2A). This pattern of glomerular volume was also evident in the subset of biopsy sections with %GSG <5% in all three regions or %GSG >10% in all three regions (Supplemental Figure 3). Thin cortex associated with more %GSG than thick cortex, although this was predominately due to differences in the superficial region (Figure 2B). Among kidneys with a thick cortex, the superficial/middle region and middle/deep region had glomerular volume and %GSG more similar to the middle region than the superficial or deep region (Figure 2). Overall, those with thick cortex were 5.5 years younger, more obese, taller, had higher eGFR, and were more likely to be smokers compared with those with thin cortex. The two groups had similar proteinuria, similar prevalence of hypertension and diabetes, and similar tumor size (Supplemental Table 2).
Comparison of microstructural findings in three cortical regions
Nonsclerotic glomerular volume and percentage of glomerulosclerosis depends on the cortical depth. (A) In each of the three cortical regions (superficial, middle, and deep), glomerular volume was larger in patients with thick (n=406) than thin (n=386) cortex. The additional two regions were in those with thick cortex (superficial/middle and middle/deep) had glomerular volumes that were more similar to the middle region than the superficial or deep region. (B) The %GSG was higher in thin than thick cortex, although this was more evident in the superficial region. Among the biopsy sections with thick cortex, the superficial/middle and middle/deep region had %GSG that was more similar to the middle region than the superficial or deep region. Data presented with mean±1 SD.
Association of Clinical Characteristics with Glomeruli by Depth
Glomerular volume, at all depths, did not vary with age, except for a modest decline after about age 70 years (Figure 3A). The age-dependent increase in %GSG and percentage ischemic glomeruli occurred more rapidly in the superficial compared with the deeper regions (Figure 3, B and C). The association of clinical characteristics with glomerular volume across cortical depths is presented in Table 3. Clinical characteristics that independently associated with larger glomerular volume included taller height, larger BMI, hypertension, diabetes, proteinuria, and smoking. These associations were similar at different depths of cortex, except for BMI, which associated more strongly with larger glomeruli that were more superficial. There was no association between age and glomerular volume at any depth, although the test for interaction was significant (P=0.02). Among those with a thick biopsy section, a similar pattern was seen across the three middle regions (Supplemental Table 3). Clinical characteristics that independently associated with higher %GSG at all depths were hypertension, lower eGFR, and higher urine protein (Table 4). Older age associated more strongly with %GSG that was superficial, proteinuria more strongly associated with %GSG that was in the middle, and diabetes associated with %GSG that was deep. Among those with a thick biopsy section, %GSG did not differ in its association with age, proteinuria, or diabetes across the three middle regions (Supplemental Table 4).
Age-related differences in nonsclerotic glomerular volume and percentage glomerulosclerosis in superficial, middle, and deep regions. (A) The glomerular volume was log transformed and plotted against age. Throughout the age spectrum, middle glomeruli (dashed line) were larger than both deep glomeruli (solid line) and the superficial glomeruli (dotted line). Smooth fits are shown, but by linear regression, there is smaller glomerular volume with older age; superficial glomerular volume declined −1.8% per 10 years (P=0.12), middle glomerular volume declined −3.1% per 10 years (P=0.002), and deep glomerular volume declined −2.4% per 10 years (P=0.02). (B) After age 50 years, superficial regions had a faster increase in percentage globally sclerotic glomeruli (%GSG) with age. With a linear fit, the superficial glomerulosclerosis increased 6.2% per 10 years and middle glomerulosclerosis increased 1.9% per 10 years, whereas in the deep region it increased 1.2% per 10 years (P<0.001 for all). (C) The percentage ischemic glomeruli increased faster with age in the superficial than in the middle or deep regions of cortex. With a linear fit, the superficial ischemic NSG increased 1.5% per 10 years (P<0.001), middle ischemic NSG increased 0.6% per 10 years (P=0.003), whereas in the deep region ischemic NSG increased 0.4% per 10 years (P=0.05). Gray shaded areas represent 95% confidence intervals around the smoother fits. NSG, nonsclerotic glomeruli.
Multivariable-adjusted association of clinical characteristics with glomerular volume in three cortical regions among 812 patients with renal tumor
Multivariable-adjusted association of clinical characteristics with level increase in %GSG category in three cortical regions among 812 patients with renal tumor
Association of Other Structural Pathology with Glomeruli by Depth
Glomerulosclerosis in glomeruli that were more superficial associated more strongly with ischemic glomeruli that were more superficial (Table 5). Arteriosclerosis also associated more strongly with glomerulosclerosis that was more superficial, whereas interstitial fibrosis did not show differences in its association with glomerulosclerosis by depth. Glomerulosclerosis and ischemic glomeruli that are superficial associated more strongly with deeper glomerular volume (Supplemental Table 5). The pattern by depth was no longer statistically significant with nonischemic glomerular volume rather than just glomerular volume (Supplemental Table 6). Interstitial fibrosis >25% was associated with smaller glomeruli at all depths, whereas arteriosclerosis was not associated with glomerular volume at any depth (Supplemental Table 5).
Unadjusted associations of %GSG category in three cortical regions with other biopsy pathology
Discussion
This study found evidence for three (and only three) distinct populations of glomeruli by depth in the human kidney. The pattern of glomerular volume and glomerulosclerosis by cortical depth was not monotonic from superficial to deep, but was u-shaped. Specifically, the middle region glomeruli were larger and had less glomerulosclerosis than did the superficial or deep region glomeruli. In those with a thicker cortex, the patterns of glomerular volume and glomerulosclerosis were similar between superficial/middle, middle, and middle/deep, suggesting that these three regions could be viewed as one middle region. The adjacent capsule for superficial glomeruli and the adjacent medulla or arcuate artery for deep glomeruli may play a role in structurally differentiating these glomerular populations from the middle region glomeruli.
Interestingly, the pattern of glomerular volume (largest in middle, intermediate in deep, and smallest in superficial) was the opposite of the pattern of glomerulosclerosis (highest in superficial, intermediate in deep, and lowest in middle) by cortical depth. This pattern of glomerular volume by cortical depth was consistent between thick and thin cortex and between low or high amounts of glomerulosclerosis. Thus, this pattern seems to hold across a wide spectrum of chronic pathology. Thicker cortex manifested larger nephrons detected by larger glomeruli (though larger tubules are likely responsible for the thicker cortex).18 The pattern of glomerulosclerosis by cortical depth was consistent with thick or thin cortical thickness but not across the age spectrum. In older individuals (>50 years) glomerulosclerosis was highest in the superficial region, whereas differences in glomerulosclerosis by depth were less evident in younger patients. More glomerulosclerosis, particularly among superficial glomeruli, associated with thinner cortex.
Our finding that superficial glomeruli were smaller than deep glomeruli is consistent with prior animal6−8 and human autopsy studies.11−13,15 However, published studies in human autopsy kidneys (n=24)14,24 and monkeys (n=6)9 did not identify middle glomeruli as the largest. We found that regardless of the degree of glomerulosclerosis, middle glomeruli were largest, followed by deep glomeruli, and superficial glomeruli were smallest. A study of human fetal kidneys at different gestational stages found glomerular size to increase from the superficial to deep regions.27 It is possible that middle glomeruli become larger than the deep glomeruli after birth. Although there was an age-related increase in superficial glomerulosclerosis, there was no evidence that glomerular volume increased with age at any depth.
There was a “disease-related” pattern of glomerular pathology that was diffuse and less related to cortical depth (Figure 4). Specifically, the association of most CKD risk factors and markers (diabetes, hypertension, smoking, and proteinuria) with glomerular volume did not differ by cortical depth. Hypertension is known to be associated with glomerulomegaly.28,29 Rodent studies have associated hypertension with larger deep glomeruli,30,31 but we did not observe that in this human study. Likewise, the associations of several CKD risk factors and markers (hypertension, lower eGFR, and interstitial fibrosis) with glomerulosclerosis did not differ by cortical depth. Interstitial fibrosis is only modestly associated with aging alone,18 but is the hallmark pathology of CKD.32,33
A conceptual model for how clinical characteristics are associated with glomerulosclerosis by depth. Age most strongly associates with superficial glomerulosclerosis and diabetes with deep glomerulosclerosis, whereas hypertension, lower GFR, proteinuria, and interstitial fibrosis are associated with glomerulosclerosis in all three cortical regions to a similar extent. Empty circles denote nonsclerotic glomeruli, and black filled circles denote globally sclerotic glomeruli.
Several unique patterns of glomerular pathology were also observed in the current study. First, there was a specific “age-related” pattern of glomerular pathology (Figure 4). Glomerular volume does not increase with age at any depth and there was a modest decline in the very elderly. There was a marked increase in both glomerulosclerosis and ischemic glomeruli in the superficial cortical region with aging. More superficial glomerulosclerosis co-segregated with more superficial ischemic glomeruli. The association of more superficial glomerulosclerosis with arteriosclerosis is further evidence of an ischemic pathway. Because afferent arterioles of deep glomeruli are larger than arterioles of superficial glomeruli,34 there may be less ischemia in deep compared with more superficial glomeruli with arteriosclerosis. Deep glomeruli may also have a vascular supply that is proximal to the arteriosclerosis detected. Arteriosclerosis is not always evident with CKD, but is a hallmark pathology of aging. Superficial glomerulosclerosis with a thin cortex is consistent with the cortical volume loss that occurs with aging.18 Second, although diabetes associated with larger glomerular volume similarly across all depths, diabetes preferentially associated with glomerulosclerosis in the deep region. A potential explanation for this is that the enlarged glomeruli have glomerular hypertension that exerts hemodynamic stress on the surface of glomerular capillary wall,35 and that glomerular capillary pressure is highest in deep region.36 Finally, obesity associated with larger glomeruli that were more superficial, and proteinuria associated more strongly with middle glomerulosclerosis, both for unclear reasons.
This study had some limitations. The studied patients all had a tumor in the sectioned kidney, though we found no association of tumor size with glomerular volume or glomerulosclerosis. We used the Weibel and Gomez25 stereological model to calculate mean glomerular volumes. This model uses a coefficient of 1.382 (assumption that glomeruli are spheres) and a coefficient of 1.01 (assumption of 10% variation in the distributions of glomerular volume within a biopsy section). Formalin fixation and paraffin embedding lead to a significant degree of glomerular volume shrinkage,37 but occurred in all wedge sections, and was unlikely to have differentially biased the observed associations. Since this study was limited to a single large wedge biopsy section, serial sections were not available to identify glomeruli that may be atubular.38 The studied population was predominantly white, which did not allow meaningful assessment of race differences.
In summary, this study observed three populations of glomeruli defined by their cortical depth. Cortical depths with larger glomerular volume tend to have less glomerulosclerosis and vice versa. Most clinical characteristics are associated with glomerular volume and glomerulosclerosis to a similar extent in all three cortical regions. Important exceptions are age-related superficial glomerulosclerosis that appears to be driven by ischemia, and diabetic glomerulosclerosis in deep glomeruli. Clinically, a needle core biopsy in an older patient that shows glomerulosclerosis adjacent to the capsule should consider the possibility of this being an age-related finding rather than evidence of chronicity for a kidney disease.
Disclosures
Dr. Lieske reports grants and other from Alnylam, grants from Dicerna, grants from Retrophin, grants from Oxthera, grants from Siemens, other from Orfan, grants and other from Allena, outside the submitted work. Dr. Kremers reports grants from National Institutes of Health (NIH), during the conduct of the study; grants from AstraZeneca, grants from Roche, grants from Biogen, outside the submitted work. Dr. Rule reports grants from NIH/National Institute of Diabetes and Digestive and Kidney Diseases, during the conduct of the study. All of the remaining authors have nothing to disclose.
Funding
This study was supported with funding from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK090358). Dr. Denic was supported by the Robert W. Fulk Career Development Award Fund in Nephrology Research Honoring Dr. Fernando Fervenza.
Supplemental Material
This article contains the following supplemental material online at http://jasn.asnjournals.org/lookup/suppl/doi:10.1681/ASN.2019020183/-/DCSupplemental.
Supplemental Figure 1. Percent fibrosis area was calculated by dividing the sum of all IF/TA areas (black traces) with a biopsy cortex area (green trace). Examples of different degrees of fibrosis are shown: A) 0%, B) 2.2%, C) 5.3%, and D) 45%. All four images were taken at the same magnification.
Supplemental Figure 2. An example of a wedge section with asymmetric cortex thickness that allowed continuous demarcation of superficial, middle and deep regions, but not 2 additional regions (superficial/middle and middle/deep).
Supplemental Figure 3. Non-sclerotic glomerular volume in superficial, middle and deep regions in different subsets of patients with minimal or profound glomerulosclerosis. Non-sclerotic glomeruli were consist entlylargest in middle region compared to superficial and deep regions among 104 patients with less than 5% glomerulosclerosis in all three regions, and among 130 patients with more than 10% glomerulosclerosis in all three regions. Data presented as mean ± standard deviation.
Supplemental Table 1. Number of patients and the mean number of non-sclerotic glomerular (NSG) profiles and globally-sclerotic glomerular (GSG) profiles per patient by each age group.
Supplemental Table 2. Clinical characteristics and biopsy findings of patients with thin and thick cortex.
Supplemental Table 3. Multivariable-adjusted association of clinical characteristics with glomerular volume in three mid-cortical regions among 406 tumor patients with thick cortex.
Supplemental Table 4. Multivariable-adjusted association of clinical characteristics with %GSG categories in three mid-cortical regions among 406 tumor patients with thick cortex.
Supplemental Table 5. Unadjusted associations of glomerular volume in three cortical regions with nephrosclerosis.
Supplemental Table 6. Unadjusted associations of non-ischemic glomerular volumes in three cortical regions with nephrosclerosis.
Acknowledgments
We thank Miloš Denić for assistance with computer algorithms for processing of biopsy annotations data.
Dr. Denic and Dr. Rule designed the study. Dr. Denic, Dr. Ricaurte, Dr. Narasimhan, and Dr. Thompson collected or provided the data. Dr. Denic, Mr. Lopez, Dr. Kremers, and Dr. Rule analyzed the data. Dr. Denic and Dr. Rule drafted the manuscript, and all authors contributed to revisions and approved the final version of the manuscript.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
- Copyright © 2019 by the American Society of Nephrology
References
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