Nephrosclerosis-Related Histopathological Findings by Cortical Region From a Japanese Community-Based Study.

Rationale & Objective: Nephrosclerosis is a major cause of end-stage kidney disease. However, few studies have addressed the association between kidney function and nephrosclerosis-related histopathologic findings because most cases of nephrosclerosis are diagnosed based on clinical signs without a kidney biopsy. Study Design: Cross-sectional study. Setting & Participants: Autopsy specimens of kidneys were obtained from 181 individuals who died within 6 years of a community-wide health examination in 2007 and who had an autopsy at the time of death. Exposure: Histopathologic findings, including glomerular, tubulointerstitial, and vascular lesions, were evaluated as outcome variables in relation to estimated glomerular filtration rate. The kidney cortex in each specimen was divided into 3 equally spaced cortical regions (superficial, middle, and juxtamedullary cortex) to assess depth-dependent lesion distribution. Outcomes: Glomerular, tubulointerstitial, and vascular lesions were evaluated in cortical regions at different depths. Analytical Approach: Associations between estimated glomerular filtration rate levels and the extent of histopathologic findings based on cortical region were tested using generalized linear mixed-effects models. Results: The present study included 172 autopsied cases (mean age: 81 years; men: 50%). The extent of histopathologic lesions progressed significantly with worsening kidney function, and the association was similar in each cortical region. Analysis based on cortical region showed significant gradients in the extent/severity of nephrosclerotic lesions, with global glomerulosclerosis and interstitial fibrosis and tubular atrophy dominating in the superficial cortex and arterial intima-media thickness and arteriolar hyalinosis dominating in the juxtamedullary cortex. The cortical region specificity of histopathologic findings in nephrosclerosis became less prominent with worsening kidney function. Limitations: Participants were elderly, and the causal relationship between pathologic findings and renal dysfunction could not be determined. Conclusions: The present study confirms a cortical region--dependent gradient of nephrosclerotic lesions within the kidney and suggests that arterial and tubulointerstitial lesions may be more strongly linked with kidney dysfunction than glomerular lesions.