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Sarcopenia is a degenerative syndrome mainly characterized by the atrophy of skeletal muscle,along with the decrease of muscle strength and function.Chronic kidney disease,especially in patients undergoing maintenance hemodialysis,can accelerate muscle consumption and increase the incidence rate of sarcopenia.Several factors were correlated with sarcopenia occurrence in chronic kidney disease,including inflammation,malnutrition,increased angiotensin Ⅱ,abnormal insulinsignaling pathway,abnormalities in myogenic regulatory factors,decreased hypogonadism,increased myostatins,mitochondrial disorders,decreased physical activity,etc.This paper has reviewed the research progress on the pathogenesis of sarcopenia in chronic kidney disease.
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Objective To evaluate the association between serum 25-hydroxyvitamin D3 [25 (OH)D3] and arterial stiffness in patients with chronic kidney disease (CKD).Methods Three hundred patients with CKD were included,and were divided into two groups based on serum 25(OH)D3 levels:vitamin D deficient [25(OH)D3 ＜ 20 μg/L] and vitamin D non-deficient [25(OH)D3≥20 μg/L].Brachial ankle pulse wave velocity (baPWV),which reflected arterial stiffness,was calculated using the single-point method.Clinical data were collected in details.Correlation between serum 25(OH)D3 level and baPWV was assessed by the single factor correlation test and multiple linear regression analysis.Results The prevalence of vitamin D deficiency was 62.7％(188/300).The concentration of 25(OH)D3 was (17.62±8.54) μg/L in total patients,but was (12.38±4.55) μg/L and (26.44±6.05) μg/L in the subgroups of vitamin D deficient and non-deficient,respectively(P ＜ 0.01).There was a higher value of baPWV in the group of vitamin D deficient than that of vitamin D non-deficient (1 827.34±429.11 vs 1 555.31 ±353.14,P ＜ 0.01).Serum 25(OH)D3 level and baPWV was negatively correlated in total patients(r=-0.38,P ＜ 0.01) and each stage of CKD(stage 2-5)[r=-0.30,P ＜ 0.05; r=-0.26,P ＜ 0.05; r=-0.46,P ＜ 0.01; r=-0.57,P ＜ 0.01].Multiple linear regression analysis showed that vitamin D level was independently associated with baPWV(Model 1:β=-0.18,P ＜ 0.01; Model 2:β=-0.17,P=0.01).Both models accounted for 50％ (R2=0.50) of total variance of baPWV.Conclusions Vitamin D deficiency is common in CKD,and a low 25(OH)D3 level is significantly associated with increased arterial stiffness in these patients.Clinical intervention studies are needed to clarify whether treatment with vitamin D decreases the risk of cardiovascular disease in patients with CKD.
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[ ABSTRACT] AIM:To investigate the effect of paricalcitol ( P) on renal tubulointerstitial fibrosis and the under-lying mechanisms in diabetic nephropathy ( DN) .METHODS:DN rat model was induced by a single intraperitoneal in-jection of streptozotocin after fasting.The animals were randomly divided into 2 groups: the DN rats in paricalcitol-inter-vened group ( group P) were injected intraperitoneally with paricalcitol dissolved in propylene glycol after the day when the model was induced successfully at a dose of 0.4μg/kg (3 times a week);the DN rats in DN group ( group D) were given isopyknic propylene glycol.Normal control group ( group C) was also set up.The samples of blood, urine and renal tissue were collected after intervention of paricalcitol for 12 weeks.The biochemical indexes were measured.The renal tissues were used for pathologic observation and determining the expression of transforming growth factor-β1 (TGF-β1), Wnt-4,β-catenin and Klotho by immunohistochemistry and Western blotting.In addition, the correlation among the above indexes was analyzed.RESULTS:(1) Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D ( P<0.05 ) .( 2 ) The area of renal tubulointerstitial fibrosis in-creased in group D compared with group C, while decreased in group P compared with group D (P<0.05).(3) The ex-pression of Klotho decreased, while the expression of TGF-β1, Wnt-4 and β-catenin increased in group D compared with group C (P<0.05).Compared with group D, the expression of Klotho increased, while the expression of TGF-β1, Wnt-4 andβ-catenin decreased in group P (P<0.05).(4) The expression of Klotho was negatively correlated with the fibrosis area, TGF-β1, Wnt-4 andβ-catenin (P<0.05).CONCLUSION:Paricalcitol inhibits renal tubulointerstitial fibrosis in DN by promoting the expression of renal Klotho, and inhibiting Wnt/β-catenin signaling pathway activation and TGF-β1 synthesis.
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Epithelial-mesenchymal transition ( EMT) , a process by which differentiated epithelial cells under-go a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury.However, the degree to which renal tubular epithelial EMT contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent.Renal tubular EMT is an adap-tive response of epithelial cells to a hostile or changing microenvironment and is regulated by many factors.Several intrace-llular signal transduction pathways such as transforming growth factor-β( TGF-β)/Smad and Wnt/β-catenin signaling are essential in controlling the process of renal tubular epithelial EMT which are potential targets of antifibrotic therapy present-ly.This review highlights the current understanding of renal tubular epithelial EMT and its underlying mechanisms to stimu-late further discussion on its role in the pathogenesis of renal interstitial fibrosis.