Analysis of pathological data of renal biopsy at one single center in China from 1987 to 2012 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In China, the prevalence of chronic kidney disease has increased significantly. Many studies shows that the spectrum of kidney disease had changed in recent years. We retrospectively analyzed the pathological types of renal biopsy and its spectrum change at the General Hospital of the Chinese People's Liberation Army from December 1987 to December 2012, in order to offer new supporting evidences for further specifying the distribution of renal pathological types in China.</p><p><b>METHODS</b>According to the "Revised Protocol for the Histological Typing of Glomerulopathy" (WHO, 1995), pathological diagnosis of renal biopsy was classified, detection rate of each pathological type was summarized (i.e., percentage of total renal biopsy cases), study period was divided at an interval of 5 years, and age-stratified distribution change of main pathological types was analyzed.</p><p><b>RESULTS</b>The proportion of pathological types in 11 618 cases of renal biopsy was as follows: primary glomerulonephritis (PGN, 70.7%), secondary glomerulonephritis (SGN, 20.7%), tubular-interstitial nephropathy (4.0%), hereditary/rare nephropathy (0.3%), end-stage renal disease (0.9%), and unclassified renal disease (3.3%). Among PGN, there was IgA nephropathy (IgAN, 37.0%), membranous nephropathy (MN, 11.8%), mesangial proliferative glomerulonephritis (MsPGN, 8.9%), minimal change disease (MCD, 6.6%), and focal segmental glomerulosclerosis (3.9%). Among SGN there was lupus nephritis (LN, 5.5%), Henoch-Schönlein purpura glomerulonephritis (5.3%), hepatitis B virus-associated nephritis (HBVAN, 3.03%), diabetic nephropathy (2.2%), and hypertension/malignant hypertension-associated renal damage (1.9%). Pathological data were analyzed from 1987-1992 to 2008-2012 (after age adjustment). Detection rate of IgAN tended to rise (P < 0.001). Detection rates of MN and MCD rose significantly (P < 0.001), but detection rate of MsPGN dropped significantly (P < 0.001). Among SGN, detection rate of HBVAN tended to drop (P < 0.001).</p><p><b>CONCLUSION</b>In China, PGN was the most common glomerulopathy (mostly IgAN), LN was the most common SGN, and detection rate of MN and MCD rose significantly.</p>

Effects of TIMP-1 on PTEN expression on renal tubular epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in regulating both angiogenesis and the expressions of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and vascular endothelial growth factor (VEGF)/Flk-1 expression in human proximal tubular epithelial cells (HKC).</p><p><b>METHODS</b>HKC cells were transfected with two recombinant plasmids containing sense and antisense full-length TIMP-1 cDNA (TIMP-1S-pcDNA3.0 and TIMP-1AS-pcDNA3.0, respectively) constructed previously, or treated with 100 µmol/L MMP-2/MMP-9 inhibitor III (with similar cellular enzyme suppression activity with sense TIMP-1 plasmid). The mRNA expression of TIMP-1, MMP-2, MMP-9, PTEN, VEGF and Flk-1 were examined by RT-PCR. In each group, the expression of PTEN, VEGF and Flk-1 were also detected using an indirect immunofluorescence assay.</p><p><b>RESULTS</b>Compared with non-transfected cells and cells transfected with the empty vector, sense TIMP-1-transfected cells showed obviously upregulated PTEN expression (P<0.05) and significantly lowered gelatinase activity (P<0.05) and VEGF and Flk-1 expressions (P<0.05). Transfection with the antisense TIMP-1 plasmid produced the reverse results (P<0.05). MMP-2/MMP-9 inhibitor III did not obviously affected the expression of PTEN, VEGF or Flk-1 as compared with the non-transfected or empty vector-transfected cells.</p><p><b>CONCLUSION</b>In the aging progress, the renal tissues express high levels of TIMP-1 to upregulate PTEN expression via a MMP-independent pathway, and subsequently down-regulates the expression of VEGF and Flk-1 to cause aging-related impairment of renal angiogenesis. These findings provide new evidence for understanding the role of TIMP-1 in renal aging.</p>

Clinicopathological features of IgA nephropathy associated with malignant hypertension and their correlation to renal vascular lesions / 中华肾脏病杂志

Objective To explore the clinicopathological features of IgA nephrolpathy associated with malignant hypertension (IgAN-MHT) and to analyze their correlation with renal vascular lesions. Methods Twenty-nine patients of IgAN-MHT were screened from 2000 biopsy-proven eases with primary IgA nephropathy (IgAN) in our department from April 1997 to May 2007. Data of clinicopathology and follow-up of these 29 patients were collected. Semi- quantitative analysis was performed to evaluate the pathological changes. Inner lumen, outer lumen, intimal thickness, tunica media-to-internal lumen ratio of 436 arterioles, 124 interlobular arteries and 5 arcuate arteries were measured. The primary endpeint was the composite of a doubling of serum creatinine level and ESRD. Correlations of renal vascular lesions with clinical manifestation, pathological change and prognosis were examined by Spearman and Cox methods. Results 1.5% of all the IgAN patients presented malignant hypertension. The common clinical features were renal failure (100%), hyperurieacidemia (62.7%) and hypertriglyceridemia (51.7%). The average amount of urine protein excretion was 2.8 g/d. The common pathological changes were moderate mesangial proliferation, severe global sclerosis, severe interstitial inflammation and severe interstitial- tubular fibrosis. The small arteries (arcuate arteries and interlobular arteries) and arterioles (afferent arterioles) were both involved in IgAN-MHT. The characteristic lesions of intrarenal arteries included vascular occlusion, media thickening, proliferative endarteritis (onionskin lesion, musculomucoid intimal hyperplasia), hyaline arteriosclerosis, but mainly vascular occlusion (86.2%). The arteriole lesion was negatively correlated with age and total protein level; vascular occlusion was positively correlated with uric acid level. The average foUow-up period was 21.1 months. Forteen patients reached the endpoint. The arteriole lesion was the main independent risk factor for the progression of IgAN-MHT (RR=10.21, 95%CI=1.16～89.67). Conclusions The main clinical feature of IgAN-MHT is renal failure. The main histological feature of intrarenal vascular lesions is occludes arterioles. Arteriole lesion is the main independent risk factor for the progression of IgAN-MHT.

Aging changes of gelatinase activity in kidney tissue of autoimmune MRL/lpr mice / 中华病理学杂志

<p><b>OBJECTIVE</b>To determine whether increased expressions of gelatinases occur with aging in vivo in kidney tissue of autoimmune MRL/lpr mice by in situ zymography.</p><p><b>METHODS</b>MRL/lpr mice at the age of 8 weeks, 16 weeks and 24 weeks were investigated. Kidney protein extracts were compared for activities of MMP-2/9 by gelatin zymography. Immunohistochemistry and SDS-PAGE gelatin zymography were used to determine the expressions and activities of gelatinase A (MMP-2) and gelatinase B (MMP-9). To determine the net gelatinase activities in murine lupus kidney, in situ zymography was used with autoradiographic emulsion as substrate.</p><p><b>RESULTS</b>Both gelatinase A and B were seldom detected in the kidney tissue in 8 week old mice, Increased expressions of both latent and activated form enzymes of MMP-2/9 were identified in kidney extraction by SDS-PAGE gelatin zymography and immunohistochemical staining showed both MMP-2 and MMP-9 were obviously up-regulated within glomerulus as well as tubular-interstitium in mice at the age of 16 and 24 weeks. In situ zymography showed markedly increased gelatinase activities in kidney tissue consistent with the results of immunohistochemical staining, it is mainly derived from MMPs and inhibited by EDTA but not by PMSF or aprotinin.</p><p><b>CONCLUSIONS</b>These in vivo results suggested that MMP-2/-9 expressions were significantly up-regulated with aging in murine lupus nephritis, which may play an important role in promoting the remodeling formation of ECM and thus contribute to the progression of renal damage in this model.</p>

Changes in activation of thrombin receptor in renal tissues of senile rats / 解放军医学杂志

Objective To determine the changes in expressions of thrombin receptor and fibrin deposit in glomeruli during the process of senility. Method Rats were divided into 3 groups (8 rats in each group): 3-month-old group (3m), 12-month-old group (12m) and 24-month-old group (24m). Fibrin deposition was detected by Martius-Scarlet-Blue staining and direct immunofluorecence method. Immunohistochemical studies were performed to detect the expression of thrombin receptor (PAR-1) and transforming growth factor-? (TGF-?). Semi-quantitative PCR was performed to detect the changes in PAR-1 mRNA expression. A quantitative analysis of the expressions was performed by image analysis system. Result Significant pathological changes were found in glomeruli during the process of senility. Fibrin deposition was not observed in glomeruli in different groups. Significant expression of PAR-1 was found in glomerular endothelial cells, mesangial cells and epithelial cells in 3m rats. On the contrary, in 24m rats, PAR-1 expression in glomeruli was significantly decreased. Expression of TGF-? was increased with senility in glomeruli. PAR-1 gene expression, barely detectable in control tissue, was strikingly increased in 24m rats. Conclusion Thrombin receptor activation could be found in glomeruli of senile rat, and it is independent of fibrin deposition. Activation of PAR-1 may play an important role in the process of renal senility.

Study of the clinico-pathological characters of acute, chronic aristolochic acid nephropathy and the pathological mechanism / 中华检验医学杂志

Objective To investigate the clinico-pathological characters of acute and chronic Aristolochic acid nephropathy, and analysis the pathological mechanism of chronic Aristolochic acid nephropathy.Methods 26 cases of aristolochic acid nephropathy diagnosed in our department were examined. They were divided into acute and chronic group by their pathological characters. Immunohistochemical staining for the expression of collagen III, PAI-1, TIMP-1 and PCNA was done in renal biopsy specimens.Results There were 11 acute cases and 15 chronic cases. Compared with acute cases, there were more female, longer duration of the medicine intake[ (142.3?52.7 months of chronic cases and 4.5 ? 2.7 months of acute cases), higher degree of hypertension[(156.7?32.4) mm Hg of chronic cases and 127.3?24.2 mm Hg of acute cases], 24 hour urinary protein,anemia, glomerulosclerosis, tubular atrophy, interstitial fibrosis and artery lesions in chronic patients(Pall

Role of type I plasminogen activator inhibitor in mediating renal tubulointerstitial injury of patients with IgA nephropathy / 中华肾脏病杂志

Objective To explore the role of type 1 plasminogen activator inhibitor (PAI-1 ) in mediating renal tubulointerstitial injury of patients with IgA nephropathy. Methods The mRNA and protein production of PAI-l in renal tubulointerstitium were defected using in stiu hybridization and immunohistochemistry. Detections of antigens of ?-smooth muscle actin(?-SMA) and proliferating cell nucleus antigen (PCNA) were also performed. Results PAI-l was normally expressed in the walls of vessels and distal tubules, but significantly increased in lesions of IgA nephropathy, including crescents, Bowman capsules and tubulointerstitial infiltrating cells. There was lithe expression of PAl-1 in the glomerular capillary tufts. The renal expression of PAI-l was significantly correlated with serum creatinine (P

Research of the expression of Na+/dicarboxylate cotransporters in renal tissue of IgA nephropathy / 中华肾脏病杂志

Objective To study the change of human Na+/dicarboxylate cotransporters (NaDC)in IgA nephropathy,and to discuss its role in IgA nephropathy. Methods Thirty-four cases of IgA nephropathy diagnosed by renal biopsy were divided into five grades according to the degree of pathological change of IgA nephropathy,and their tubulointerstitial lesions were semi-quantitatively analyzed. Changes of the expression of NaDC1 and NaDC3 in kidney were observed by using immunohistochemistry,and analyzed with clinical data by correlation. Results Tubulointerstitial lesion exacerbated with the progress of pathological change in IgA nephropathy. In the cases of Ⅳ and Ⅴ grade,24 h urinary protein,serum creatinine,urinary NAG enzyme were increased,and urinary osmotic pressure was decreased,as compared with the cases of Ⅰ-Ⅲ grade( P

Investigation of the expression of proliferating cell nuclear antigen of retinal pigment epithelial cells after experimental retinal detachment and reattachment in cats / 中华眼底病杂志

Objective To examine the expression of proliferating cell nuclear antigen (PCNA) of retinal pigment epithelial (RPE) cells, thus assessing the role of mechanism of contact inhibition playing in the process of experimental retinal detachment and reattachemnt. Methods Retinal detachment was produced in 72 cats by subretinal injection of 0.25% solution of healon through a micropipette three weeks after extracapsular lens extraction and vitrectomy. Some of the detached retinae were reattached 24 hours later. At different time, the cats were killed and eye globes were fixed and embeded in paraffin. Histologic sections were processed for immunohistochemistry examination using an antibody to detect PCNA protein. Labeled RPE cells were identified, and the proliferation was quantified in detached and un detached retinae of detachment group, and also in reattached retinae of reattachment group. The comparsion of PCNA labeled RPE cells in different groups were analyzed by ANOVA. Results In detached regions of detachment group, PCNA expression of RPE cells occured within 24 hours, and reached a maximum after 5 6 days, then gradually declined to barely detectable levels after 20 days. Similar tendency was found in reattached retinae, but the number of PCNA labeled RPE cells was obviously small. Fewer PCNA labeled RPE cells were found in regions of un detached retinae in detachment group. The difference of these three groups was significant. Conclusion Proliferation of RPE cells is induced when they lose contact with neural retina, but inhibited after neural retina reattached to RPE cells. It suggests that the mechanism of contact inhibition plays a role in the proliferative process after retinal detachment and reattachment.