Chinese Journal of Nephrology

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A retrospective analysis of clinicopathology and plasma complement activation in C3 glomerulonephritis

YU Xiao-juan;LIU Gang;ZHAO Ming-hui.

2011, 27(11): 797-801.

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Objective To study the clinicopathological features of C3 glomerulonephritis and the associations between plasma complement fragments level and clinical manifestations. Methods The clinical and pathological data of the 12 patients with C3 glomerulonephritis in our division from January 1999 to June 2010 were analyzed retrospectively. Concentrations of plasma factor B, Ba, C3, C3a, C4a and C5a were detected by commercial available sandwich ELISA kits on the day of renal biopsy. Results Ten of the 12 patients were C3 glomerulonephritis without MPGN, and the rest 2 were C3 glomerulonephritis with MPGN. All the patients presented proteinuria. Two of the 10 C3 glomerulonephritis patients without MPGN presented nephrotic range proteinuria, 6 with microhematuria, 1 with gross hematuria, and 2 with renal insufficiency. One of the 2 C3 glomerulonephritis patients with MPGN presented nephrotic range proteinuria, accompanied by microhematuria, hypertension and renal insufficiency. The other patient showed moderate proteinuria with normal renal function. Most of C3 glomerulonephritis patients without MPGN showed mild mesangial proliferative glomerulonephritis, and 4/10 patients had various degree cresentic formation. One C3 glomerulonephritis patient with MPGN had 47.1% cresentic formation. The concentration of plasma C3 in C3 glomerulonephritis patients was normal, while the plasma factor B was significantly decreased, and the concentrations of plasma Ba, C3a, C4a and C5a were significantly elevated. The concentration of plasma Ba was positively correlated with the proteinuria level, while the concentrations of plasma C3a, C4a and C5a were not correlated with the levels of proteinuria or plasma creatinine. Conclusions Majority of these 12 patients were C3 glomerulonephritis without MPGN, manifests as nephritic syndrome clinically and mild mesangial proliferative glomerulonephritis histopathologically. Complement activation via alternative pathway may play an important role in the pathogenesis of C3 glomerulonephritis.

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Relationship of serum cystatin C level with cytokines and carotid atherosclerosis in maintenance hemodialysis patients

WU Bi-bo*;ZHANG Li-ming;MEI Chang-lin;TANG Qi;YU Yong.

2011, 27(11): 802-806.

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Objective To investigate the serum cystatin C (CysC) level and explore its relationship with cytokines and atherosclerosis (AS) in maintenance hemodialysis (MHD) patients. Methods A total of 110 stable MHD patients undergoing hemodialysis for at least six months and 60 healthy control people were enrolled in the study. Serum levels of CysC and high-sensitivity C-reactive protein (hsCRP) were measured by immunoturbidimetry. The serum levels of total homocysteine (tHcy), IL-1β, IL-6 and TNF-α were determined by ELISA. Prevalence of atherosclerosis was detected by carotid ultrasonography. The relationship of CysC level and cardiac geometry incidence in MHD patients was analyzed by Logistic regression model. Results The serum CysC level was significantly higher in MHD patients as compared with healthy controls [(6.19±0.95) mg/L vs (0.76±0.21) mg/L, P<0.01], and the serum levels of hsCRP, tHcy, IL-1β, IL-6, TNF-α were significantly higher in MHD patients than those in healthy control group (P<0.05 or P<0.01). The serum CysC level was higher in MHD patients with carotid artery atherosclerosis compared to patients without carotid artery atherosclerosis (P<0.05). CysC was positively correlated with hsCRP, tHcy, IL-1β, IL-6, TNF-α respectively (P<0.05 or P<0.01), and was positively correlated with carotid intimal medial thickness (IMT) and AS. Besides, a negative correlation was found between the serum CysC level and the serum albumin level (P<0.05), while CysC was positively correlated with dialysis duration, systolic pressure and iPTH (P<0.05). Conclusion Serum CysC level is significantly higher in MHD patients and is correlated with hsCRP, tHcy, IL-1β, IL-6, TNF-α as well as carotid artery atherosclerosis, which indicates that CysC is an independent risk factor of AS in MHD patients.

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Association of vascular calcification and gremlin expression in radial arteries of patients with stage 5 of chronic kidney disease

GONG Li-feng;LU Jing-kui;TANG Wei-gang;JIANG Wei;MA Gui-xiang.

2011, 27(11): 807-810.

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Objective To study the association of the expression of bone morphogenetic protein (BMP) antagonist gremlin and vascular calcification in radial arteries of patients with stage 5 of chronic kidney disease (CKD). Methods Radial arteries of 40 patients with stage 5 of CKD were collected as specimens of the study group, which were trimmed off during arterial venous fistula operations. Splenic trabecular arteries were collected as specimens of the control group, which were removed from 38 patients with simple traumatic splenic rupture. All the arteries were examined histologically for calcification with von Kossa stain. Expressions of gremlin and BMP-2, -7 were detected by immunohistochemistry and their serum concentrations were detected by ELISA. Images of histological sections were semi-quantitatively analyzed by Image-Pro Plus 6.0. SPSS 19.0 software was used to perform statistical analysis. Results Significantly positive von Kossa stain was found in radial arteries from 12 of 40 patients (30%) in study group, which located in the layer of medial smooth muscle cells. However, there was no obvious positive stain in control group. Additionally, in study group, significant expressions of gremlin and BMP-2 were detected in those radial arteries of positive von Kossa stain, which also located in the layer of medial smooth muscle cells. Positive correlations were found among gremlin expression level, BMP-2 expression level and von Kossa stain intensity. However, the BMP-7 expression intensity in arteries of study group was much weaker as compared to control group. Conclusions Both gremlin and BMP-2 may be involved in the process that the smooth muscle cells of radial arteries in patients with stage 5 of CKD phenotypically transform into osteoblast-like cells. However, BMP-7 possibly prevents this process.

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Renal tubular epithelial phenotypic transdifferentiation in renal allograft rejection

ZHANG Li-hong;SUN Ya-xin;ZHANG Cheng-bin;WU Dan;CHEN Shuang;GAO Bao-shan;ZHOU Hong-lan;WU Shan;WANG Yong.

2011, 27(11): 811-814.

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Objective To observe the transdifferentiation of renal tubular epithelial phenotype in allograft biopsy samples of patients with various rejections, and to analyze the association between rejection and transdifferentiation. Method Immunohistochemistry (SP method) was applied to detect α-SMA expression in tubular epithelial cells from 55 renal allograft biopsy samples with various rejection. Results Positive α-SMA expression was found in all the atrophic tubular epithelial cells adjacent to cytoplasm of basement membrane, which indicated the atrophic renal tubular epithelial cells appeared the phenotypic transdifferentiation. Positive α-SMA was also detected in some renal epithelial cells without atrophy. No phenotypic change was found in 7 cases without obviously rejection. Among 28 cases of acute T-cell-mediated rejection IA grade, α-SMA positive expression rate of non-atrophy renal epithelial cells was 25%-50% in 1 case and 10%-25% in 3 cases. Among 14 cases of more severe acute rejection group IB grade, α-SMA positive expression rate was over 50% in 1 case, 25%-50% in 2 cases and 10%-25% in 2 cases. Conclusion When acute T-cell-mediated rejection becomes more serious in renal allograft, the phenotype transdifferentiation aggravates in renal tubular epithelial cells.

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Death causes and risk factors of uremia patients

LAI Han;GAN Hua;LI Ge;YANG De-xiang.

2011, 27(11): 815-818.

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Objective To investigate the death causes and risk factors of uremia patients in order to improve the prognosis of uremia patients. Methods Clinical data of 247 uremia inpatients and outpatients from 2001 to 2011 in our hospital were retrospectively analyzed. Dead patients were served as death group (n=124) and survival patients as control group (n=123). Death causes and primary disease were studied. Frequency of hemodialysis, prealbumin, albumin, natremia and pulmonary infection were compared between two groups. Results Age and gender were not associated with the death of uremia patients. The most common cause of death was cardiovascular disease followed by respiratory failure，uremic encephalopathy, cerebral hemorrhage, gastrointestinal hemorrhage, etc. Hemodialysis frequency, prealbumin, albumin and natremia of dead patients were obviously lower than those of control group. More patients in death group suffered from pulmonary infection. Logistic multivariate analysis revealed that death risk increased by 40.7% when reducing 1 time per week of hemodialysis; death risk increased by 53.4% when reducing 50 mg/L of prealbumin; death risk increased by 14.6% when reducing 5 mmol/L of blood sodium; death risk of patients with pulmonary infection increased by 15.06 times of patients without pulmonary infection; death risk of diabetes mellitus increased by 4.26 times of patients without diabetes mellitus. Conclusions Cardiovascular disease, respiratory failure, uremic encephalopathy, cerebral hemorrhage, and gastrointestinal hemorrhage are common causes of death in uremia patients. Hemodialysis frequency, prealbumin, hyponatremia, pulmonary infection and diabetes can be regarded as risk factors for death of uremia patients.

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Correlations of ABCA1 with foam cells formation in renal interstitium, tubulointerstitial lesion and serum cholesterol

SU Hua;FU Ling;LIU Jian-she;ZHU Hong-yan.

2011, 27(11): 819-824.

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Objective To investigate the correlations of ATP-binding cassette transporter A1 (ABCA1) protein expression in renal interstitium with foam cells formation, tubulointerstitial lesion and serum cholesterol in glomerulonephropathy. Methods Five patients with Alport syndrome, 28 patients with membranous proliferative glomerular nephritis (MPGN), 35 patients with focal segmental glomerulosclerosis (FSGS), 36 patients with idiopathic membranous nephropathy (IMN) and 34 patients with IgA nephropathy (IgAN) were enrolled in the study. Expression of ABCA1 protein was detected by immunohistochemical method. The relative area of foam cells in renal interstitium was semi-quantified and the correlations of ABCA1 protein expression in renal interstitium (except for renal tubules) with the relative area of foam cells, integration of tubulointerstitial lesion (TIL) and serum cholesterol were examined using t test and linear correlation analysis. Results In renal interstitium, monocyte-macrophages, foam cells and renal tubular epithelial cells expressed ABCA1 protein. ABCA1 protein expression in renal interstitium with foam cells infiltration was significantly higher as compared to that without foam cells infiltration (P< 0.05), but there was no correlation between ABCA1 expression and foam cells area (P>0.05). In MPGN, FSGS, IMN patients, there was a positive correlation between ABCA1 protein expression in renal interstitium and integration of TIL (P<0.05). There was a positive correlation between serum cholesterol level and ABCA1 protein expression in renal interstitium (P<0.05). Conclusions In glomerulonephropathy, cholesterol may promote the ABCA1 expression in renal interstitium. ABCA1 may have double-effects on transportation of cholesterol. ABCA1 may take part in the process of tubulointerstitial lesion.

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Role of NF-κB in monocytes-induced HK-2 cells transdifferentiation

LI Qing;LV Lin-li;ZHENG Min;MA Kun-ling;ZHANG Xiao-liang;LIU Bi-cheng.

2011, 27(11): 825-830.

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Objective To investigate the effects of monocytes on phenotypic changes of human proximal tubular HK-2 cells and the mechanism. Methods Monocytes were co-cultured with HK-2 cells. Morphological changes of HK-2 cells were detected by inverted phase contrast microscope. Expressions of E-cadherin, α-SMA and fibronectin were assessed by RT-PCR, Western blotting and immunocytochemical staining. Flow cytometry techniques was applied to evaluate intercellular cell adhesion molecule-1(ICAM-1) expression on HK-2 cells. The intracellular signal was investigated by gene microarray. Results The typical epithelial cell morphology of HK-2 cells disappeared after co-culture with monocytes, accompanied by decreased E-cadherin expression and increased α-SMA and fibronectin expression (all P<0.05). The expression of ICAM-1 on HK-2 cells was increased by monocytes stimulation. Interestingly, administration of CD18 antibody directly inhibited the phenotypic change of HK-2 cells. Furthermore, NF-κB signaling might be critical in mediating this process, and blockade of this signaling pathway could inhibit ICAM-1 expression and epithelial–mesenchymal transition(EMT) formation. Conclusion Monocytes can directly induce EMT of HK-2 cells via up-regulating ICAM-1 through NF-κB signaling pathway.

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Effect of high glucose on renin-angiotensin system in rat glomerular endothelial cells and its associated mechanism

XING Yan-fang;PENG Hui;LI Can-ming;YE Zeng-chun;LI Ming;LOU Tan-qi.

2011, 27(11): 831-837.

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Objective To explore the effect of high glucose on the renin-angiotensin system(RAS) in rat glomerular endothelial cells and its probable mechanism. Methods Rat glomerular endothelial cells were stimulated by culture medium containing 5 mmol/L or 30 mmol/L glucose (with or without pre-treatment of captopril and chymostatin) for 12 h, 24 h, 48 h, 72 h. ELISA, real-time PCR, Western blotting and confocal immunofluorescence microscopy were employed to examine the follows: the angiotensinⅡ(AngⅡ) concentration in cell lysate and the culture medium; the mRNA levels of angiotensinogen and renin; the protein levels of angiotensinⅡ type 1 receptor (AT1R), angiotensinⅡ type 2 receptor (AT2R), renin and angiotensinogen in cell lysate; localization of intracellular AT1R, AT2R and renin. Results Exposure to high glucose for only 12 h or 72 h resulted in a significant increase of AngⅡ levels in the culture medium compared with control cells(P<0.05), but only exposure to high glucose for 72 h resulted in a significant increase of AngⅡ levels in the cell lysate compared with control cells(P<0.05). However, exposure to high glucose for 24 h or 48 h had no effects on AngⅡ levels in the cell lysate or culture medium. The captopril and chymostatin were able to antagonize high glucose induced AngⅡ generation when exposure time was 72 h but not 12 h. Exposure to high glucose-increased the mRNA level of angiotensinogen, but reduced the level of renin mRNA, meanwhile angiotensinogen protein increased, and AT1 protein reduced, but protein levels of AT2R and renin were unchanged. However, the transformation of AT2R from the cell nucleus to cytoplasm was observed. Conclusions High glucose can activate the local renin-angiotensin system in rat glomerular endothelial cells, and the probable mechanism may contribute to ACE and non-ACE pathways. The effects of high glucose on glomerular endothelial cells may also involve in the substrate and receptors of AngⅡ.

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Effect of aldosterone on glomerular mesangial cells apoptosis both in vivo and in vitro

REN Zhi-long;LIANG Wei;DING Guo-hua;HU Feng-qi;YANG Hong-xia.

2011, 27(11): 838-843.

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Objective To evaluate the effect of aldosterone (Ald) on glomerular mesangial cells apoptosis and to explore the possible mechanisms. Methods Twenty-four Sprague-Dawley rats were subcutaneously embedded with osmotic mini-pumps and randomly divided into 3 groups. Aldosterone (1.5 μg/h) was administrated subcutaneouly by osmotic mini-pumps in Ald group, eplerenone (Epl, 100 mg•kg-1•d-1) and Ald (1.5 μg/h) was given to Epl group. And normal saline was used in control group (Con group). Systolic blood pressure and urinary albumin excretion rate (UAER) were detected on day 0, 7, 14, 21, 28. Blood and kidney samples were harvested on day 28. Plasma creatinine, potassium and aldosterone were measured. Renal paraffin sections were stained by PAS and the morphological changes were evaluated by light microscopy. Apoptosis index of mesangial cells were detected by TUNEL assay. The glomerular mesangial cells (MCs) were cultured in a DMEM-F12 media. MCs apoptosis was evaluated by staining cells with Annexin V and propidium iodide (PI) using flow cytometer. Expression of Bcl-2 and Bax mRNA was examined by RT-PCR. The protein level of Bad or phospho-Bad was measured by Western blotting. Results Ald-infused rats developed hyperaldosteronemia and hypokalemia. Rats in Ald group exhibited significant hypertension and marked albuminuria. Ald group rats showed increased number of TUNEL-positive mesangial cells when compared with control rats(P<0.05). Aldosterone induced mesangial cells apoptosis in a time-dependent manner. Expression of Bcl-2 mRNA was decreased but Bax mRNA was increased in aldosterone treated MCs compared to that in Con group(P<0.05). Aldosterone promoted dephosphorylation of cytosolic phospho-Bad compared with vehicle treated cells（P< 0.05）. However, eplerenone attenuated these effects of aldosterone. Conclusion Aldosterone directly promotes mesangial cells apoptosis, and eplerenone can attenuate this effect of aldosterone. Dephosphorylation of cytosolic phospho-Bad may be the key role in the progression of mesangial cells apoptosis induced by aldosterone.

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Protective effect of aliskiren on type 2 diabetic nephropathy in db/db mice

ZHOU Guang-yu;SU Xue-song;DU Feng;LI De-tian．

2011, 27(11): 844-849.

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Objective To investigate the effect of aliskiren on type 2 diabetic nephropathy in db/db mice． Methods Eight-week old db/db and db/m mice were subjected to right nephrectomy to hasten the development of diabetic nephropathy. At age of 16 weeks, they were divided into four groups: db/m group (normal control), db/db group ( diabetic control), db/db+A3 group (db/db mice treated with aliskiren 3 mg•kg-1•d-1) and db/db+A25 group (db/db mice treated with aliskiren 25 mg•kg-1•d-1). Body weight, blood glucose, glycosylated hemoglobin, proteinuria and systolic blood pressure were measured before and after treatment. After treatment, renal histological examination by PAS staining, TGF-β1 and PAI-1 protein by ELISA, expression of ColⅣ and FN protein by immunofluorescence, mRNA expression of TGF-β1, PAI-1, ColⅣ, FN and renin by real time PCR, renin activity and angiotensin Ⅱ level by radioimmunoassay were performed. Results Treatment for 4 weeks of aliskiren at a dose of 25 mg•kg-1•d-1 markedly decreased urinary albumin excretion, glomerulosclerosis and suppressed synthesis of TGF-β1, PAI-1, ColⅣ, FN without inducing significantl change in systolic blood pressure, compared to those of db/db group (all P<0.05). Aliskiren also suppressed renin activity and angiotensin Ⅱlevel in renal cortex (all P<0.05). Conclusion Aliskiren protects against type 2 diabetic nephropathy.

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Bone marrow-derived stem cells promote glomerular repair and regeneration in progressive glomerulosclerosis rat model

XING Li;ZHANG Dao-fa;SONG Shu-min;WANG Cen-cen;QI Si-hua;YANG Bao-feng;LI Bing.

2011, 27(11): 850-853.

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Objective To investigate the protective role of bone marrow-derived stem cells (BMDSCs) in progressive glomerulosclerosis rats, and to observe whether BMDSCs promote glomerular repair and regeneration. Methods Progressive glomerulosclerosis was induced in enhanced green fluorescent protein (EGFP) bone marrow chimeric rats by injecting with anti-Thy-1.1 antibody, followed by unilateral nephrectomy. Subsequently, these rats were treated with either BMDSCs infusion (treatment group, 10 rats) or phosphate-buffered saline (untreated group, 10 rats). Renal function and histological alterations were examined at week 12 after Thy1.1 antibody injection. Repair and regeneration of glomerular endothelial cells was detected by immunofluorescence. Results Only 3 rats survived in untreated group, other 7 rats died at week 2, 7, 9, 11 after antibody injection. In treatment group, 9 rats survived at week 12, only 1 rat died at week 10. The BUN and Scr were significantly lower in treatment group as compared to untreated group [BUN(43.55±29.06) vs (76.58±66.19) mmol/L, Scr (138.79±75.14) vs (233.38±164.43) μmol/L]. Proteinuria was not significantly different between two groups at day 3, 7, 14 and 28, while it was significantly decreased at day 42, 56 and 84 in treatment group compared with untreated group. Light microscopy showed that there was severe diffuse mesangial cell proliferation, mesangial matrix expansion and glomerulosclerosis in untreated group, and such changes were ameliorated in treatment group. The mesangial expansion index and glomerular sclerosis index in untreated group was significantly higher than those in treatment group. More BMDCs were recruited into the glomeruli and differentiated into glomerular endothelial cells in treatment group as compared with untreated group. Double immunofluorescence stain also demonstrated that BMDSCs infusion promoted glomerular capillary repair and regeneration. Conclusion BMDSCs infusion can improve renal function and histological changes, and promote the repair and regeneration of glomerular capillary.

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基础研究

临床研究

基础研究