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Differential synchrotron X-ray imaging markers based on the renal microvasculature for tubulointerstitial lesions and glomerulopathy.

ABSTRACT: High resolution synchrotron microtomography capable of revealing microvessels in three dimensional (3D) establishes distinct imaging markers of mouse kidney disease strongly associated to renal tubulointerstitial (TI) lesions and glomerulopathy. Two complementary mouse models of chronic kidney disease (CKD), unilateral ureteral obstruction (UUO) and focal segmental glomerulosclerosis (FSGS), were used and five candidates of unique 3D imaging markers were identified. Our characterization to differentially reflect the altered microvasculature of renal TI lesions and/or glomerulopathy demonstrated these image features can be used to differentiate the disease status and the possible cause therefore qualified as image markers. These 3D imaging markers were further correlated with the histopathology and renal microvessel-based molecular study using antibodies against vascular endothelial cells (CD31), the connective tissue growth factor or the vascular endothelial growth factor. We also found that these 3D imaging markers individually characterize the development of renal TI lesions or glomerulopathy, quantitative and integrated use of all of them provide more information for differentiating the two renal conditions. Our findings thus establish a practical strategy to characterize the CKD-associated renal injuries by the microangiography-based 3D imaging and highlight the impact of dysfunctional microvasculature as a whole on the pathogenesis of the renal lesions.

SUBMITTER: Lin YC

PROVIDER: S-EPMC5471266 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Differential synchrotron X-ray imaging markers based on the renal microvasculature for tubulointerstitial lesions and glomerulopathy.

Lin Yu-Chuan YC Hwu Yeukuang Y Huang Guo-Shu GS Hsiao Michael M Lee Tsung-Tse TT Yang Shun-Min SM Lee Ting-Kuo TK Chen Nan-Yow NY Yang Sung-Sen SS Chen Ann A Ka Shuk-Man SM

Scientific reports 20170614 1

High resolution synchrotron microtomography capable of revealing microvessels in three dimensional (3D) establishes distinct imaging markers of mouse kidney disease strongly associated to renal tubulointerstitial (TI) lesions and glomerulopathy. Two complementary mouse models of chronic kidney disease (CKD), unilateral ureteral obstruction (UUO) and focal segmental glomerulosclerosis (FSGS), were used and five candidates of unique 3D imaging markers were identified. Our characterization to diffe ...[more]

PMID: 28615647

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Project description:BackgroundRenal tubules and interstitium are vulnerable to injury and play a central role in the progression of various chronic kidney diseases (CKDs). However, high quality epidemiologic study on the profiles of biopsy-proven tubulointerstitial lesions (TILs) is extremely limited.MethodsWe conducted a retrospective renal biopsy series including 62,569 native biopsies at 1,211 hospitals across China from 2015 to 2017. The TILs, including the shedding of tube epithelial, renal tubular atrophy, renal interstitial fibrosis, edema and inflammatory infiltration, were identified from the pathological report. We analyzed the severity and chronicity of TILs stratified by gender, age groups, biopsy indications, and concurrent glomerular diseases. We also examined the correlation between TIL and glomerulosclerosis.ResultsOf 56,880 patients with biopsy-proven glomerular disease, 79.5% had TILs. Renal interstitial inflammatory infiltration was the most common type of TIL (77.7%), followed by renal tubular atrophy (56.0%) and renal interstitial fibrosis (32.8%). Severe and chronic TILs were more common in adults than in children. The three glomerular diseases with the highest proportion of moderate-to-severe and chronic TIL were diabetic nephropathy, immunoglobulin A (IgA) nephropathy and focal segmental glomerulosclerosis. The severity of TILs was moderately correlated with glomerulosclerosis score (r=0.51). Moderate-to-severe and chronic TIL were more common in southern China. After adjusting for age, sex, hospital level, region, biopsy indication and type of concurrent glomerular diseases, adults with renal arteriole injury had a six-fold higher risk of moderate-to-severe TIL [odds ratio (OR), 7.12; 95% confidence interval (CI), 6.42 to 7.91] and a three-fold higher risk of chronic TIL (OR, 4.58; 95% CI, 4.37 to 4.79).ConclusionsTILs were common in patients with biopsy-proven glomerular disease. The type and severity of TILs varied with age, region and concurrent glomerular diseases. Renal arteriole injury and glomerulosclerosis was associated with a significantly increased risk of TIL.

Project description:BACKGROUND:The presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events. However, the mechanisms leading to IPH are not fully understood. The dominant view is that IPH is caused by leakage of erythrocytes from immature microvessels. The aim of the present study was to investigate whether there is an association between atherosclerotic plaque microvasculature and presence of IPH in a relatively large prospective cohort study of patients with symptomatic carotid plaque. METHODS:One hundred and thirty-two symptomatic patients with ?2?mm carotid plaque underwent cardiovascular magnetic resonance (CMR) of the symptomatic carotid plaque for detection of IPH and dynamic contrast-enhanced (DCE)-CMR for assessment of plaque microvasculature. Ktrans, an indicator of microvascular flow, density and leakiness, was estimated using pharmacokinetic modelling in the vessel wall and adventitia. Statistical analysis was performed using an independent samples T-test and binary logistic regression, correcting for clinical risk factors. RESULTS:A decreased vessel wall Ktrans was found for IPH positive patients (0.051?±?0.011?min-?1 versus 0.058?±?0.017?min-?1, p?=?0.001). No significant difference in adventitial Ktrans was found in patients with and without IPH (0.057?±?0.012?min-?1 and 0.057?±?0.018?min-?1, respectively). Histological analysis in a subgroup of patients that underwent carotid endarterectomy demonstrated no significant difference in relative microvessel density between plaques without IPH (n?=?8) and plaques with IPH (n?=?15) (0.000333?±?0.0000707 vs. and 0.000289?±?0.0000439, p?=?0.585). CONCLUSIONS:A reduced vessel wall Ktrans is found in the presence of IPH. Thus, we did not find a positive association between plaque microvasculature and IPH several weeks after a cerebrovascular event. Not only leaky plaque microvessels, but additional factors may contribute to IPH development. TRIAL REGISTRATION:NCT01208025 . Registration date September 23, 2010. Retrospectively registered (first inclusion September 21, 2010). NCT01709045 , date of registration October 17, 2012. Retrospectively registered (first inclusion August 23, 2011).

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Differential synchrotron X-ray imaging markers based on the renal microvasculature for tubulointerstitial lesions and glomerulopathy.

Publications

Differential synchrotron X-ray imaging markers based on the renal microvasculature for tubulointerstitial lesions and glomerulopathy.

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