The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease

Eardley, Kevin S.; Kubal, Chandrashekhar A.; Zehnder, Daniel; Quinkler, Marcus; Lepenies, Julia; Savage, Caroline O. S.; Howie, Alexander J.; Kaur, Kirrenjit; Cooper, Mark S.; Adu, Dwomoa; Cockwell, Paul

doi:10.1038/ki.2008.183

Cited by 145 publications

(129 citation statements)

References 33 publications

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“…7,30 Finally, WBCs are involved in the kidney's response to injury as evidenced by leukocyte infiltration in kidney tissues of patients with CKD and in experimental models. [31][32][33] Lower mtDNA copy number might alter the role of WBCs and platelets in injury response. The inclusion of mtDNA copy number derived from WBCs and platelets in experiments investigating the role of mitochondrial dysfunction in CKD can increase our understanding on the potential role of these cells in the pathogenesis of CKD and may lead to novel insight for the prevention or treatment of CKD.…”

Section: Main Findingsmentioning

confidence: 99%

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

Tin

Grams²,

Ashar

et al. 2016

JASN

118

115

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Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P,0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P,0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.

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Section: Main Findingsmentioning

confidence: 99%

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

Tin

Grams²,

Ashar

et al. 2016

JASN

118

115

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“…Also, 1,25(OH)2D3 has been shown to inhibit macrophage chemoattractant protein-1 (MCP-1)-driven inflammatory process by blocking nuclear factor-κB activation. MCP-1 is expressed in injury and inflammation and leads to direct macrophage recruitment [12] . Hepatitis C virus (HCV) is remarkably efficient at establishing persistent infections, suggesting that HCV has evolved one or more strategies aimed at evading the host immune response.…”

Section: Introductionmentioning

confidence: 99%

Relationship between vitamin D and IL-23, IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

Husseiny

Fahmy²,

Mohamed³

et al. 2012

WJH

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AIM:To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS:The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age-and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20 ℃. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t -test for comparison of means of different parameters was used. Correlation analysis was done using Pearson's correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS:The mean vitamin D level in HCV patients (group Ⅰ) was 15 ± 5.2 ng/mL while in control (group Ⅱ) was 39.7 ± 10.8. For active vitamin D in group Ⅰ as 16.6 ± 4.8 ng/mL while in group Ⅱ was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group Ⅰ and 6.7 ± 2.17 in group Ⅱ. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group Ⅰ and 216.1 ± 5.38 in group Ⅱ. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group Ⅰa with bright hepatomegaly and included 14 patients. Group Ⅰb with perihepatic fibrosis and included 11 patients. Group Ⅰc with liver cirrhosis and included 11 patients. Group Ⅰd with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). ORIGINAL ARTICLE

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“…Inflammatory cells present in the renal interstitium include monocytes/macrophages, dendritic cells, and T and B lymphocytes (12)(13)(14)(15)(16). CD68 + macrophage accumulation and CD3 + or CD8 + lymphocyte infiltration are suggested to predict IgAN progression (12,13,15) DC-SIGN + cells, a special subset of dendritic cells that is essential for dendritic cell-induced T cell proliferation, have also been found in the kidney of different types of human GN (14). However, there is no detailed research on DC-SIGN + cells in IgAN.…”

Section: Introductionmentioning

confidence: 99%

Renal Interstitial Infiltration and Tertiary Lymphoid Organ Neogenesis in IgA Nephropathy

Pei

Zeng

Han

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Previous studies have identified inflammatory features that enable the prediction of renal outcome of IgA nephropathy (IgAN); however, validation of these findings is still needed. This prospective study was performed to determine the characteristics of renal interstitial infiltration and tertiary lymphoid organ (TLO) neogenesis in a cohort of Chinese patients with IgAN.Design, setting, participants, & measurements Adult patients with IgAN were recruited into this study from June 2009 to June 2010. Inflammatory cells in renal biopsy tissues were detected by immunohistochemistry and immunofluorescence. Correlations between the density of interstitial inflammatory cells, grades of TLOs, and clinicopathologic features were evaluated. Of 152 eligible patients, 72 (47%) were successfully followed-up by telephone at 30 months after renal biopsy. Twelve patients were classified as the severe group and 60 patients were classified as the stable group, according to the progression of serum creatinine levels during the follow-up period. A comparison of the severity of interstitial infiltration and the frequency of TLO neogenesis between the two groups was performed.Results The accumulation of interstitial inflammatory cells was correlated with decreased renal function, heavy proteinuria, and severe glomerular, interstitial, and arterial lesions in patients with IgAN. TLOs, identified as nodular inflammatory infiltrates containing organized DC-SIGN + , CD4 + , CD8 + , and CD20 + cells, were observed in 37.5% of patients. Patients with high-grade TLOs exhibited a high percentage of mesangial hypercellularity and crescents as well as severe interstitial and arterial lesions. Patients in the severe group exhibited more severe interstitial infiltration and a higher percentage of TLO neogenesis (83.3% versus 33.3%; P=0.001) compared with patients in the stable group.Conclusions As contributors to an active local inflammatory response, the severity of interstitial infiltration and the frequency of TLO neogenesis are correlated with glomerular, interstitial, and arterial lesions as well as IgAN progression.

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The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease

Cited by 145 publications

References 33 publications

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

Relationship between vitamin D and IL-23, IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

Renal Interstitial Infiltration and Tertiary Lymphoid Organ Neogenesis in IgA Nephropathy

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