Chinese Journal of Nephrology

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Blood pressure rhythm and its association with clinicopathological indices in patients with IgA nephropathy

XU Da-min;LV Ji-cheng;LIU Li-jun;SHI Su-fang;ZHANG Hong.

2012, 28(5): 350-354.

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Objective To investigate the blood pressure circadian rhythm in patients with IgA nephropathy by ambulatory blood pressure monitoring and explore its role in the disease progression. Methods A cross sectional study was carried out. Blood pressure rhythm was studied by ambulatory 24-hour monitoring with a portable oscillometric recorder in selected patients with primary IgA nephropathy. The term "dipper" was described as blood pressure during night dropped at least 10% below daytime blood pressure． The term "non-dipper" referred to those in whom the nocturnal decline in blood pressure was less than 10%． Clinicopathological indices between dipper and non-dipper groups were compared. Results Ninety-three patients completed ambulatory blood pressure monitoring among whom 68(73%) patients were non-dipper. The frequency of non-dipper was 70%, 70% and 81% in the patients at chronic kidney disease stage 1，2 and 3 or more. The frequency did not differ among these three group patients (P=0.587). 77% of patients with hypertension and 69% of patients with normotension were non-dipper (P=0.373). The disappearance of blood pressure circadian rhythm in IgA nephropathy was not influenced by age, gender, blood pressure, proteinuria, renal function and renal pathology lesions. Among the patients who were followed up regularly for more than 12 months (n=54), patients in the dipper group had a trend of slower eGFR decline rate than those in non-dipper group albeit the difference was not significant (P=0.329). Subgroup analysis revealed that in patients with hypertension and non-dipper (n=29), the eGFR decline rate was much faster than that in dipper group[(-6.79±11.58）vs (-0.34±1.74) ml•min-1•(1.73 m2）-1•year-1, P=0.019]. Conclusions Most patients with IgA nephropathy present disappearance of blood pressure circadian rhythm, even among those at an early stage or without hypertension. The loss of blood pressure rhythm may be associated with a rapid renal function decline rate in those with hypertension.

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Association of fibroblast growth factor 23 with coronary artery calcification in patients with moderate and advanced stage chronic kidney diseases

YAN Jia-yi;ZHANG Min-fang;NI Zhao-hui;YIN Yan;ZHU Ming-li;MOU Shan;WANG Qin;FANG Wei;ZHANG Wei-ming;YAN Yu-cheng;QIAN Jia-qi.

2012, 28(5): 355-360.

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Objective To elucidate the association of fibroblast growth factor 23 (FGF23) with coronary artery calcification in patients with moderate and advanced stage chronic kidney diseases (CKD). Methods Serum intact FGF23 levels in 150 patients with CKD stage 3 to 5 and 25 age- and sex-matched healthy controls were measured by ELISA. The association between FGF23 and coronary artery calcification was studied. Results Serum FGF23 levels in CKD patients were significantly higher than those in healthy controls [196.46 (83.09, 355.02) ng/L vs 27.17 (21.63, 51.20) ng/L, P<0.01]. The levels of FGF23 were significantly higher in dialyzed patients than those in non-dialyzed patients (P<0.01), and hemodialysis patients had higher levels as compared to peritoneal dialysis ones [6048.29 (1129.08, 34807.45) ng/L vs 1625.80 (602.83, 7521.78) ng/L, P<0.01]. The incidence of coronary artery calcification was relatively high in patients with moderate and advanced stage CKD (74/130, 56.9%). Serum FGF23 level was positively correlated with coronary artery calcification score (CaS) (r=0.177, P<0.05). Logistic regression analysis showed that age (β=0.091, OR=1.095, P<0.01), duration of dialysis (β=2.013, OR=7.483, P<0.05) and FGF23 level (β=0.838, OR=2.311, P<0.05) were independent risk factors for coronary artery calcification in patients with moderate and advanced stage CKD. ROC curve of coronary artery calcification revealed that area under curve (AUC) of FGF23 was 0.705 (P<0.01). With the cut-off value of FGF23 as 786.73 ng/L, the diagnostic sensitivity and specificity in coronary artery calcification were 62.5% and 75.9%. ROC curve of coronary artery calcification showed that AUC of alkaline phosphatase (AKP) was 0.626 (P=0.017). With the cut-off value of AKP as 79.75 U/L, the diagnostic sensitivity and specificity in coronary artery calcification were 84.5% and 41.5%. There was no diagnostic value of serum phosphorus in coronary artery calcification. Conclusions Serum FGF23 level is correlated with coronary artery calcification in patients with moderate and advanced stage CKD. The sensitivity of FGF23 is lower and the specificity is higher than those of AKP for the diagnosis of coronary artery calcification.

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Value of urine L-FABP and its combination with urine NGAL in early diagnosis of acute kidney injury after cardiac surgery in adults

LIU Shang;CHE Miao-lin;XIE Bo;XUE Song;ZHU Ming-li;LU Ren-hua;ZHANG Wei-ming;QIAN Jia-qi;NI Zhao-hui;YAN Yu-cheng.

2012, 28(5): 361-366.

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Objective To investigate the value of urinary liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL) and their combination in predicting the development and the severity of acute kidney injury (AKI) following cardiac surgery in adults. Methods Scr, urinary L-FABP and NGAL corrected by urine creatinine at preoperation, 0 h and 2 h postoperative time points were examined. The differences of above indexes between AKI and non-AKI groups were compared. Receiver operating characteristic (ROC) curves and area under curves (AUC) were used to evaluate the diagnostic value of urinary L-FABP, NGAL and their combination for AKI. Results The cohort consisted of 109 patients, 26 (23.9%) developed AKI, and AKIN stage Ⅰ, Ⅱ and Ⅲ was 46.2%, 34.6% and 19.2% respectively. Levels of urinary L-FABP and NGAL were significantly higher in AKI patients at 0 h and 2 h postoperatively. AUC to predict AKI or AKI stage Ⅱ-Ⅲ was 0.81 to 0.87 using either of the biomarkers. The performance of combining two biomarkers was better with AUC of 0.911 to 0.927. Conclusions Urinary L-FABP and NGAL increase at the early stage after cardiac surgery. Combination of these two biomarkers enhances the accuracy of the early diagnosis of postoperative AKI after cardiac surgery before a rise of Scr.

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Combining uric acid with lipoprotein a predicts the atherosclerotic renal artery stenosis in high risk patients

XIA Peng;QIU Ling;ZENG Yong;CHEN Li-meng;ZENG Xue-jun;LI Xue-mei;LI Xue-wang.

2012, 28(5): 367-370.

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Objective To explore the value of uric acid (UA) combined with lipoprotein a [Lp(a)] in prediction of atherosclerotic renal artery stenosis (ARAS) in high risk population with atherosclerosis. Methods A total of 190 patients who were highly suspected for ARAS and received renal artery angiography in Peking Union Medical College Hospital from October 2008 to April 2011 were enrolled in the study. Among these patients, 120 were diagnosed as coronary arterial disease (CAD) by coronary artery angiography and 89 were diagnosed as ARAS. The control group included 180 people undergoing routine healthy examination in our hospital. The basic information and lab results such as UA, Lp(a), total cholesterol (TC), triacylglycerol (TG), HDL, LDL, Scr and C-reactive protein (CRP) were collected. Logistic regression analysis was used to identify possible risk factors of ARAS and to establish a new tool to predict ARAS in the high risk population. Results The levels of Scr, UA, Lp(a) and CRP in ARAS cases were significantly elevated compared to control people. For high risk population, there were no significant differences in Scr, lipids, UA and CRP between ARAS cases and non-ARAS cases. Logistic regression analysis showed that UA level>344 μmol/L was correlated to ARAS independently. Using UA level>344 μmol/L and Lp(a) level>242 mg/L as a predicting marker for ARAS in high risk population, the specificity was 96.0%, the positive likelihood ratio was 5.45 (P=0.001), and the odds ratio was 6.78, 95%CI (1.90~24.2) (P=0.001). Conclusions In high risk population, the UA may be an independent correlating factor of ARAS. Combining UA with Lp(a) can predict the ARAS.

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Correlation between serum proteasome and endothelial dysfunction in patients with uremia

LUO Zhi-feng;FENG Bing;ZENG Wei;GUO Yan-hong;PANG Qi;CHEN Ji-gang;MU Jiao;LI Yan;NIE Ling;YUAN Fa-huan;FENG Bing.

2012, 28(5): 371-376.

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Objective To investigate the correlation between plasma proteasome and endothelial dysfunction in patients with uremia. Methods Forty-five uremic patients who did not receive hemodialysis were defined as A group; seventy-five uremic patients who had received hemodialysis for 6 to 12 months were divided into sufficient hemodialysis group (44 cases, B group) and insufficient hemodialysis group (31 cases, C group). The primary disease of these patients was chronic glomerulonephritis. Fifteen healthy people were defined as healthy control group (D group). The diameter of radial artery lumen (DRL), intima-media thickness (IMT), intima-media area (IMA), endothelium-dependent or independent dilation (EDD or EID) of radial artery in right forearm were detected by diasonography. The levels of 20S proteasome, tumor necrosis factor α（TNF-α）, C-reaction protein (CRP) and transforming growth factor β 1 (TGF-β1) of plasma and supernatant of cultured human umbilical veins endothelium (HUVEC) were determined by enzyme linked immunosorbent assay (ELISA). 20S proteasome activity was analyzed by special substrate. Results Compared with D group, the level and activity of 20S proteasome, as well as TNF-α, CRP and TGF-β1 in A, B and C groups were significantly increased. Compared with A group, these plasma indices levels were significantly decreased in B group but strongly increased in C group. IMT and IMA were elevated, while DRL, EDD and EID were decreased significantly in A, B and C groups when compared with D group. These parameters were worse in C group than those in A and B groups. After co-culture of HUVEC with above mentioned human uremic serum, the level and activity of 20S proteasome and TNF-α were higher in A, B, C groups than that in D group. In A and C groups, there were negative correlations of EDD with the level or activity of 20S proteasome, TNF-α, CRP and TGF-β1, and there were positive correlations of 20S proteasome level or activity with TNF-α, CRP and TGF-β1. Conclusions 20S proteasome level and activity are significantly increased in uremic patients. There is a close correlation between 20S proteasome and endothelial dysfunction of radial artery.

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Heart protection of L-carnitine in chronic renal failure rats

ZHANG Li-ming;TANG Qi;MEI Chang-lin; LU Yi-zhou;WU Bi-bo.

2012, 28(5): 377-382.

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Objective To investigate the effect of L-carnitine on pathological changes of myocardium and the underlying mechanism in chronic renal failure rats (CRF). Methods A total of 55 male SD rats were randomly divided into sham group (n=10), model group(n=15), low dose (300 mg/kg), medium dose (600 mg/kg) and high dose (900 mg/kg) L-carnitine group(n=10, each). 5/6 subtotal nephrectomy was performed in these rats without sham group. One week after the operation, normal saline or corresponding dose L-carnitine were intragastrically administrated to sham and model group or L-carnitine groups for 17 weeks. Transthoracic echocardiography, mean arterial pressure (MAP), heart rate (HR) and heart weight/body weight were assessed. Moreover, 24 h urine protein, renal function, SOD, MDA, IL-6, ATP, ADP were measured at the end of the study. Additionally, pathological changes in myocardium were detected by light microscope and transmission electron microscope. Results (1) ATP(μmol/g•wt)in L-carnitine groups (2.35±0.24, 3.59±0.28，3.78±0.25) was significantly higher than that in model group (1.61±0.12) (all P<0.01). (2) Thickness of posterior wall of left ventricle (mm) in high dose L-carnitine group was thinner than that in model group (3.74±0.23 vs 4.18±0.48, P<0.05). (3) The ratios of heart weight to body weight in both medium dose and high dose L-carnitine groups (3.92±0.27, 3.65±0.2) were significantly lower compared to model group(3.99±0.27) (all P<0.01). (4) Under light microscopy, disarrangement and hypertrophy of cardiac myocytes, increased myocardial fibrosis were observed in model group, while these changes and the pathological scores were significantly improved in both medium dose and high dose L-carnitine groups (7.14±1.07, 6.13±0.99), as compared with model group(9.88±1.13) (all P<0.01). Under electron microscopy, typical changes in cardiac hypertrophy were observed, including dissolution of myocardial fibers, increasing and swelling of mitochondria, membrane rupture as well as matrix increase in model group, while these changes were ameliorated by L-carnitine in a dose-dependent manner. (5) Seventeen weeks after the treatment, both IL-6 and MDA were decreased in all L-carnitine-treated groups than those in model group[IL-6(ng/L): 261.86±13.18, 240.12±18.7, 233.34±36.88 vs 596.64±81.41; MDA（nmol/L）: 15.23±2.01, 12.41±0.6, 10.97±1.9 vs 21.84±2.71). Whereas, SOD (U/ml) were increased in L-carnitine-treated groups (51.2±6.11, 58.51±5.52, 60.63±6.94) than that in model group（32.01±5.69）(all P<0.05). (6) No significant differences of systolic, diastolic blood pressure or MAP were found among groups. Conclusion L-carnitine can improve energy metabolism, micro-inflammation and oxidative stress in myocardium of CRF rats, which may be associated with the amelioration of cardiac hypertrophy and fibrosis.

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Impact of malnutrition and inflammation status on hospitalization and mortality in maintenance hemodialysis patients

WANG Wen-long;LIU Mao-sen;WANG Hui-ling;LI Yun-sheng;CHENG Yong-Jun;KE Ying-jie;LIN Hua-zhi;WU Guang-hua.

2012, 28(5): 383-387.

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Objective To investigate the impact and the associated parameters of malnutrition and inflammation status on hospitalization and mortality of maintenance hemodialysis (MHD) patients. Method A total of 118 MHD patients were included in the study with 1 year’s follow-up. The malnutrition and inflammation parameters were compared between the hospitalized patients and out-patients. Cox’s proportional hazard regression model was used to explore the malnutrition and inflammation parameters which could forecast the risk of hospitalization and mortality. Result The hospitalization rate of MHD patients with mild, moderate and severe malnutrition was 32.93%, 56.67% and 83.33% respectively, and the mortality was 3.66%, 6.67% and 80.00% respectively. The hospitalization rate of MHD patients with or without micro-inflammation status was 56.45% and 46.43%, and the mortality was 14.29% and 1.61%. Inpatients had a higher malnutrition-inflammation score(MIS, 8.36 vs 5.86, P<0.05) and subjective global assessment of nutrition (MQSGA,14.49 vs 12.88, P<0.05), a lower creatinine level (886.83μmol/L vs 991.76 μmol/L, P<0.05） and a lower albumin level (38.57 g/L vs 40.27 g/L, P<0.05) than out-patients. Inpatients also had a higher level of TNF-α (65.41 μg/L vs 59.76 μg/L, P<0.05) than out-patients. Cox proportional hazard model analysis showed that MIS and TNF-α were associated with patient’s first hospitalization risk. Conclusions For the MHD patients, the more severe the malnutrition and micro-inflammation status is, the worse the clinical outcome is. The higher levels of MIS and TNF-α result in greater risk of hospitalization.

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Expression of serum microRNA-192 in the diabetic nephropathy patients and its impact on TGF-β signaling pathway

LI Jie;ZHOU Ping;HU Xiu-mei;PENG You-ming.

2012, 28(5): 388-391.

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Objective To detect the expression of serum microRNA (miR)-192 in diabetic nephropathy (DN) patients and investigate its effects on DN. Methods The serum levels of miR-192 and miR-210 in DN patients, diabetic patients without renal injury and healthy people were detected by real-time quantitative PCR. Down-stream target genes were predicted using TargetScan software and further confirmed by gain of function and loss of function studies in vitro. Mesangial cells were treated with different concentrations of TGF-β1, then miR-192 expressions of cells and supernatant were examined as well. Results Serum miR-192 level significantly decreased in DN patients compared with healthy people (0.41±0.09 vs 1.00±0.00, P＜0.01) and diabetic patients without renal injury, while the serum miR-210 levels were not significantly different among three groups. Bioinformatics analysis results showed that some target genes were involved in TGF-β signal pathway. ZBP1, IGF-1 and type I collagen (ColⅠ) were chosen and confirmed by Western blotting, which were regulated by miR-192. TGF-β1 decreased the expression of miR-192 in both cells and cell culture supernatants. Conclusion Serum miR-192 may promote the progress of DN by regulating TGF-β1 signaling pathway and may be used as a potential biomarker in the diagnosis of DN depending on its certain specificity.

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Effects of rosiglitazone on the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in renal interstitial fibroblasts induced by cyclosporine A

LI Hai-jian;CHENG Gen-yang;LIU Zhang-suo.

2012, 28(5): 392-396.

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Objective To investigate the effects of rosiglitazone on the expression of peroxisome proliferator-activated receptor-γ(PPARγ) and matrix metalloproteinase-9(MMP-9) in renal interstitial fibroblasts induced by cyclosporine A, and discuss renal protective effect of rosiglitazone on renal toxicity of cyclosporine A. Methods Construction, screening and amplification of the target siRNA vector for PPARγ were carried out. The inhibitory effect of siRNA on the expression of PPARγ in normal rat kidney(NRK) cells was evaluated. NRK cells were cultured in the routine way. Experimental groups: (1)control group: single NRK cells without treatment; (2)RGZ group: NRK cells with RGZ (10 μmol/L); (3)CsA group: NRK cells with CsA (1.0 mg/L); (4)CsA+RGZ group: NRK cells with CsA (1.0 mg/L) plus RGZ (10 μmol/L); (5)CsA+RGZ+siRNA group: pRNAT-U6.2/Lenti-PPARγ-236 plasmid transfected into NRK cells, then CsA (1.0 mg/L) plus RGZ (10 μmol/L). The mRNA expression of PPARγ was detected by real-time RCR. The mRNA expressions of MMP-9 and TIMP-1 were detected by RT-RCR. The protein expression of FN was detected by Western blotting. Results CsA up-regulated the mRNA level of PPARγ, MMP-9 and TIMP-1 (P<0.05), and the up-regulation was inhibited by RGZ significantly (P<0.05). The application of PPARγ siRNA resulted in the decreasing of PPARγ mRNA (P<0.05), and partly reversed the inhibition effect of RGZ on MMP-9 and TIMP-1 mRNA (all P<0.05). CsA up-regulated the protein level of FN (P<0.05), and this effect was significantly inhibited by RGZ (P<0.05). The application of PPARγ siRNA could reverse the inhibition effect of RGZ on FN protein expression (P<0.05). Conclusion RGZ can inhibit the expressions of FN, MMP-9 and TIMP-1 induced by CsA which may be the mechanism of the protective effect of RGZ on renal interstitial fibrosis induced by CsA.

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The glomerular microRNA expression profile in spontaneous type 2 diabetes KKAy mice and the effect of losartan treatment

FAN Qiu-ling;ZHANG Cong-xiao;LIU Xiao-dan;YANG Gang;JIANG Yi;DONG Xue-zhu;FENG Jiang-min;MA Jian-fei;ZHANG Yu-xia;WANG Li-ning.

2012, 28(5): 397-402.

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Objective To identify susceptible miRNAs for the pathogenesis of diabetic nephropathy(DN) and the molecular targets of losartan treatment. Methods The 8-week age KKAy mice were divided into losartan treatment group(10 mg•kg-1•d-1) and non-treatment group, C57BL/6 mice were used as the control group. At age of 20 weeks, body weight, random blood glucose, urinary albumin and urinary creatinine were tested, and kidney morphology was observed. Glomeruli were separated by magnetic beads perfusion, and total RNA were extracted. MiRNAs expression profiles were analyzed by the Affymetrix GeneChip miRNAs arrays. Results At age of 20 weeks, KKAy mice developed higher body weight, higher blood glucose and higher urinary microalbumin creatinine ratio than C57BL/6 mice, and the glomerular basement membrane thickened, mesangial matrix widened. Losartan treatment markedly improved the level of urinary albumin creatinine ratio [(539.71±100.23) mg/g vs (728±177.19) mg/g, P<0.05)] and pathological lesion of KKAy mice. The miRNA array analysis showed that there were 22 miRNAs differentially expressed between KKAy non-treatment mice and C57BL/6 mice glomeruli at age of 20 weeks. Among them, 10 miRNAs were up-regulated, and 12 miRNAs were down-regulated. The expression of 4 miRNAs was down-regulated in glumeruli of KKAy mice treated by losartan compared with that of non-treatment mice. The expressions of miRNA-503 and miRNA-181d were significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment. Conclusion The expressions of miRNA-503 and miRNA-181d are significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment, which may be new therapeutic targets of DN.

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肾脏病与心血管专题

临床研究

基础研究

肾脏病与心血管专题

临床研究

基础研究