Clinical-pathological features and prognosis of thrombotic tbrombocytopenic purpura in patients with lupus nephritis / 中华风湿病学杂志

Objective To investigate the clinical-pathological features, treatment and prognosis of thrombotic thrombocytopenic purpura in patients with lupus nephritis (LN). Methods A retrospective ana-lysis was carried out based on the clinical-pathological data for the treatment and prognosis of eight patients with LN related TIP. All patients had thrombocytopenia and hemolytic anemia, neurological symptoms and renal dysfunction. Six patients had fever. Results All 8 patients had sudden-onset of rapid progressive glomeurlonephritis (RPGN), one patient with continuous gross hematuria, the pathological features of these patients revealed TMA lesions. Immune suppressive therapy was initiated and blood purification therapy were applied in seven patients. Three cases had plasmapheresis and (or) immunoabsorption. One case was lost during follow-up, the other seven patients were followed with period at one year. One patient died, three patients went into peritoneal dialysis in which one of them was changed to hemodialysis finally. The other three patients had stable renal function. Conclusion The LN patients with TTP had severe clinical-patho-logical changes, rapid progressive and poor outcome, so we should diagnose and treat these patients as early as possible.

Rhein inhibits transforming growth factor beta1 induced plasminogen activator inhibitor-1 in endothelial cells / 中华医学杂志(英文版)

<p><b>OBJECTIVES</b>To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor beta1 (TGFbeta1), and to explore the mechanism of the protective action of rhein on endothelial cells.</p><p><b>METHODS</b>A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 was determined by immunoprecipitation analysis and western blot.</p><p><b>RESULTS</b>TGFbeta1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFbeta1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 in human endothelial cells.</p><p><b>CONCLUSIONS</b>Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.</p>

Regional citrate anticoagulation in critically ill patients during continuous blood purification / 中华医学杂志(英文版)

<p><b>OBJECTIVES</b>To evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding tendencies.</p><p><b>METHODS</b>Forty critically ill patients being treated by continuous blood purification (CBP) were involved in this study. Due to their bleeding tendencies, regional citrate anticoagulation treatment was given to all of them. Those with hepatic function impairment (n = 10) were classified as Group A, those with hypoxemia were classified as Group B (n = 10), and the others as Group C (n = 20). Blood samples were collected before treatment, and at 4, 12, 24, 36, and 48 hour intervals during CBP. These samples then were used arterial blood gas analysis, whole blood activated clotting time (WBACT) pre- and post-filter, and serum ionized calcium examination.</p><p><b>RESULTS</b>WBACT pre-filter showed little fluctuant through the 48 hr period of CBP, and WBACT post-filter showed obvious prolongation than that of the pre-filter (P < 0.05) at all time points. Metabolic acidosis was found in Group A patients before CBP, and improved during CBP. Normal acid-base conditions of patients were disturbed and deteriorated in Group B during CBP, but not in Group C. Serum ionized calcium was maintained at a normal range during CBP in Group A and C patients, but declined significantly in Group B patients (vs. pre-treatment, P < 0.05).</p><p><b>CONCLUSIONS</b>Regional citrate anticoagulation can be safely used in conjunction with CBP treatment for patients with hepatic function impairment, but may induce acidosis and a decline in serum ionized calcium when used with hypoxemic patients.</p>

Construction of an angiopoietin-like protein 2 expression vector and its expression in human endothelial cells / 医学研究生学报

Objective: To construct an angiopoietin-like protein 2(ANGPTL2) expression vector and obtain ANGPTL2 over-expression endothelial cell strains.Methods: Plasmid phrGFP-C was used to amplify hrGFP protein coding sequence by polymerase chain reaction.The amplified sequence was cloned into the A multiple cloning sites of pIRES to construct plasmid pIRES-hrGFP.Complementary oligonucleotides containing the recognition sequence of BamH I,Sal I,Xba I and SSe8387 I were synthesized,annealed and cloned into a BamH I site on the backbone of plasmid pIRES-hrGFP to obtain vector pIRES-hrGFP-MS.ANGPTL2 cDNA was cloned by RT-PCR while human renal RNA was used as the templet and then inserted into the B multiple cloning sites of the vector pIRES-hrGFP-MS.The newly constructed ANGPTL2 expression vector pIRES-hrGFP-MS-ANGPTL2 was linearized by Xba I and introduced into human umbilical vein endothelial cells.ANGPTL2 over-expressed endothelial clones were screened out by G418 selection and identified by the expression levels of both hrGFP and ANGPTL2 genes in these cell clones.Results: The ANGPTL2 expression vector pIRES-hrGFP-MS-ANGPTL2 was constructed successfully and two ANGPTL2 over-expression endothelial strains were obtained.The cells displayed a significantly extended appearance quite different from that of the control cells.Conclusion: The successful construction of the ANGPTL2 expression vector pIRES-hrGFP-MS-ANGPTL2 and the obtainment of two ANGPTL2 over-expression HUVEC strains have paved the way for further investigation into the function of ANGPTL2 and its possible role in diabetic nephropathy.

Preparation and characterization of monoclonal antibody against human angiopoietin-like protein 2 / 医学研究生学报

Objective:To prepare human angiopoietin like protein 2(ANGPTL2) monoclonal antibody.Methods:The purified recombinant human ANGPTL2 was used to immunize BALB/c mice.Then,the mouse spleen cells were isolated and fused with mouse myeloma cells.After selecting with HAT medium and analyzing with ELISA assay,the hybridoma cell clones stably secreting human ANGPTL2 antibody were screened out.The monoclonal antibody against humain ANGPTL2 was purified by ammonium sulfate precipitation method from the supernatant liquid of hybridoma cell culture.Western blotting,Cell immunostaining,and immunohistochemisty staining were used to characterize the antibody.Results:A strain of hybridoma cell clones stably secreting human ANGPTL2 antibody was screened out.The ANGPTL2 monoclonal antibody prepared was proven useful. Conclusion:A monoclonal antibody against human ANGPTL2 was successfully prepared,which provide a basis for basic study of ANGPLTL2.

The value of proteinuria analysis in multiple myeloma patients with renal involvement / 医学研究生学报

Objective:To analyze and compare the clinicopathological characteristics in low weight proteinuria(LWP) and nephrotic proteinuria(NP) multiple myeloma(MM) patients with renal involvement.Methods:From October 1991 to October 2005,46 patients with MM were diagnosed in the Research Institute of Nephrology of Jinling Hospital(Nanjing,China).Renal biopsies were done in 41 of them.The patients were devided into two groups,LWP and NP groups.Their clinical and pathological features were investigated and compared. Results:The epidemiological features and type of MM in LWP and NP groups were similar.The patients in LWP group had higher incidence of D-S Ⅲ stage and heavier anaemia compared to NP group.Compared to patients in NP group,patients in LWP group had higher incidence of renal insufficiency and lower urine osmotic pressure.Part of patients checked urine N-acetyl-?-glucosaminidase,RBP and there were no difference between two groups.Cast nephropathy was the most frequent pathologic type in LWP group,while light chain deposition disease and glomerular amyloidosis were the most common pathologic type in NP group.Conclusion:According to this study,we get the conclusion that proteinuria analysis may be a significant test to evaluate the clinicopathological characteristics of MM patients with renal involvement.

Angiopoietin-like protein 2 is specifically expressed in the renal tissues of diabetic nephropathy db/db mice / 医学研究生学报

Objective: ANGPTL2 is a newly found angiogenesis-associated protein.In the previous studies,we found that the renal expression of ANGPTL2 is involved in the development of diabetic nephropathy,but failed to reveal the exact distribution and synthesis of renal ANGPTL2.This study aimed to analyze the expression of the ANGPTL2 gene in the glomerulus and tubules in the kidney of db/db mice with diabetic nephropathy and to determine the cells responsible for the synthesis of renal ANGPTL2.Methods: Glomerulus and tubules were microdissected from the renal tissue of diabetic db/db mice and the expression of ANGPTL2 mRNA was analyzed by RT-PCR.The distribution and synthesis of ANGPTL2 in the kidney of the db/db mice were determined by immunohistochemistry,dual-labeling immunofluorescence and immunoelectron microscopy.Results: Significantly increased expression of ANGPTL2 mRNA was found in the glomeruli but not in the tubules of the diabetic db/db mice,as compared with the controls.Immunohistochemistry revealed that the ANGPTL2 protein was distributed in a podocyte-like pattern;dual-labeling immunofluorescence analysis showed colocalization of ANGPTL2 with WT1(Wilms' tumor 1,a marker of podocyte) staining,suggesting that renal ANGPTL2 was expressed specifically by podocytes,which was confirmed by immunoelectron microscopy.Conclusion: ANGPTL2 is specifically expressed by podocytes in diabetic nephropathy mice.

Continuous veno venous hemofiltration in treatment of acute necrotizing pancreatitis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effectiveness of using continuous veno venous hemofiltration (CVVH) in the treatment of acute necrotizing pancreatitis (ANP).</p><p><b>METHODS</b>Thirteen ANP patients were involved in this study, including 4 females and 9 males, averaging 50.6 +/- 10.8 years old. CT scans upon admission revealed 33% necrosis involving the body of the pancreas in 2 patients, 67% necrosis in 3 patients and 100% necrosis in the other 8; the CT severity score was 8.9 +/- 2.1. CVVH was maintained for at least 72 hours and the AN69 hemofilter (1.2 m(2)) was changed every 24 hours. The ultrafiltration rate during CVVH was 2993.9 +/- 983.0 ml/h, the blood flow rate was 250 - 300 ml/min, and the substitute fluid was infused in a pre-diluted manner. Low molecular weight heparin was used as anticoagulant.</p><p><b>RESULTS</b>CVVH was well tolerated in all the patients. Bloody abdominal cavity drainage fluid was observed in 2 patients, but no other side-effects related with CVVH were observed. Two patients died of systemic fungal infections and another died of intracranial fungi infection, resulting in an ICU mortality of 23.1%. Ten of the patients survived in the ICU, but one of them died for other reasons unrelated to the SAP before discharge. The APACHE II score before CVVH was 15.2 +/- 6.5, but decreased significantly to 8.1 +/- 5.3, 7.5 +/- 4.9 and 8.0 +/- 5.2 at the 24th, 48th and 72nd hour after CVVH, respectively (P < 0.01). Serum concentration of IL-1beta and TNFalpha decreased to the trough at the 6th hour after a new hemofilter was used and increased slowly to pre-CVVH levels 12 hours later. After CVVH had ceased, the serum levels of two cytokines increased to their peaks at the 120th hour and decreased eventually at the 144th hour. The sieving coefficient (SC) of IL-1beta and TNFalpha was 0.33 +/- 0.11 and 0.16 +/- 0.08.</p><p><b>CONCLUSION</b>CVVH offered therapeutic options for ANP and was well tolerated resulting in clearance of IL-1beta and TNFalpha; CVVH at early stages of SAP may contribute to the improvement of outcome.</p>

Pathological demography of native patients in a nephrology center in China / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To analysis the pathological demography in Chinese patients undergoing renal biopsy from our nephrology center.</p><p><b>METHODS</b>Between January 1979 and October 2000 in Jinling Hospital, Nanjing, China, 10,002 attempts of percutaneous renal were performed in patients with renal disease from 33 provinces of China. The pathological classifications were made according to the WHO criteria of 1982 for renal pathology or the modified WHO criteria of 1995 by a panel of pathologists and nephrologists during routine clinical-pathological rounds. The pathological demography between those specimens collected from 1979 - 1989 and those from 1990 - 1999 was compared.</p><p><b>RESULTS</b>The mean age of the 10,002 subjects undergoing renal biopsy was 31.4 +/- 13.0 years (ranging from 1 to 78 years), with a male to female ratio of 1.3:1; for the 592 renal transplant recipients, the mean age was 37.5 +/- 9.1 years (ranging from 16 to 66 years), with a male to female ratio of 2.36:1. Primary glomerular diseases (PGD) accounted for 71% of the total patients undergoing renal biopsies, secondary glomerular nephritis (SGN) 23%, tubular-interstitial diseases 3.2%, unclassified renal diseases 1.3%, hereditary and congenital renal diseases 1.0%, end stage renal diseases 0.96%, and recently realized or rare renal diseases 0.15%. IgA nephropathy (IgAN) was the most frequent pathological pattern (40%) of PGD, followed by mesangial proliferative lesion (MsPL) (30%), membranous nephropathy (MN) (10%), and focal segmental glomerulosclerosis (FSGS) (6%). Lupus nephritis (LN) was the most pathology common seen (74%) in SGN. During the 22 years of the study period, there was a steady increase in patients with SGN discovered during pathological evaluation of renal disorders. A rise in prevalence was found in IgA nephropathy, MN (both P < 0.001), crescentic glomerulonephritis (P < 0.0001), anti-GBM disease, and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura related renal damages (both P < 0.001). There was a decrease in endocapillary proliferative glomerulonephritis (P < 0.001) and IgM nephropathy (IgMN) (P < 0.01) from 1990 - 1999 as compared to 1979 - 1989. Infrequent renal pathological entities were also diagnosed in this group, including Niemann Pick disease, Fabry's disease, POEMS syndrome, and lipoprotein glomerulonephropathy.</p><p><b>CONCLUSIONS</b>This is the largest series of renal biopsy data in China, and therefore may reflect the demographic picture of renal diseases in this country. Changes in prevalence of renal pathological entities were reflected in this group of patients over the last 22 years. In primary glomerular diseases, IgA nephropathy is still the most frequently observed pathological pattern. In SGN, LN appeared the most often. Increased prevalence was found in anti-GBM nephritis and HUS/TTP.</p>

Clinical spectrum of diffuse crescentic glomerulonephritis in Chinese patients / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate retrospectively the incidence, distribution of primary disease and clinicopathologic characteristics of diffuse crescentic glomerulonephritis (DCGN) in Chinese patients.</p><p><b>METHODS</b>One hundred and seventy-two consecutive patients diagnosed as having DCGN out of 9828 cases of non-transplanting renal biopsies over sixteen years, were studied. DCGN is categorized into three types according to immunopathologic characteristics. The incidence of this disease, its primary diseases, clinical characteristics and serum antineutrophil cytoplasmic antibodies (ANCAs) were analyzed.</p><p><b>RESULTS</b>The distribution of patients among the three classifications was 8.7% type I, 68.6% type II and 22.7% type III. Clinically, the majority of patients (69.8%) presented rapidly progressive glomerulonephritis (RPGN), but 30.2% manifested a chronic nephritic syndrome or chronic renal failure. In terms of related conditions, 93% were anemic, 61.6% had hypertension, 50.6% oliguria, 45.3% nephrotic syndrome, 43% uremic syndrome and 39.5% displayed gross hematuria. Those patients who were positive in serum for ANCAs had predominantly type III DCGN. Two cases with anti-GBM-antibody crescentic glomerulonephritis and three with lupus nephritis were also positive for ANCAs in serum.</p><p><b>CONCLUSION</b>DCGN is not rare in Chinese patients. A majority of patients in our study presented with RPGN, but 30.2% manifested a chronic renal failure. Lupus patients with DCGN that were positive for ANCAs had more severe vasculitic lesions.</p>

Cyclosporine A in treatment of membranous lupus nephropathy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate retrospectively the efficacy of cyclosporine A (CsA) in the treatment of membranous lupus nephropathy (MLN).</p><p><b>METHODS</b>Twenty-four patients with systemic lupus erythematosus (SLE) and biopsy-proven MLN were treated with CsA in combination with prednisone. CsA was given at a starting dosage of 5 mg x kg(-1) x d(-1) for 3 months, with a 1 mg x kg(-1) x d(-1) reduction every month and then maintained at a dosage of 2 mg x kg(-1) x d(-1). The dosage of oral prednisone differed from person to person according to levels of extra-renal activity. Clinical efficacy and adverse reactions were retrospectively analyzed. Complete remission was defined as having a urinary proteinuria level (Upr) of < 0.4 g/d, and normal serum albumin and serum creatinine (SCr) levels, without SLE activity. Partial remission was defined as having a UPr decrement > 50% of baseline value and a serum albumin value of 30 - 35 g/L, without SLE activity. No response was defined as having a Upr decrement < 50% of baseline value and > 2.0 g/d, or as a deterioration of renal function, or as having active SLE.</p><p><b>RESULTS</b>One patient could no longer undergo follow-up, and the other 23 patients were treated with CsA and followed up for 6 - 36 months (mean 16.8 +/- 8.4 months). The mean starting dosage of CsA was 4.7 +/- 0.5) mg x kg(-1) x d(-1) and the trough level of the whole blood CsA was 248 +/- 110) micro g/L. Twelve patients (52.2%) achieved complete remission, 10 patients (43.3%) achieved partial remission after CsA treatment, and one patient showed no response. At different CsA treatment timepoint, the complete remission rates were 17.4% (3rd month), 21.7% (6th month), 40% (12th month), 88.9% (18th month) and 100% (24th month) respectively. SCr elevation, when within a normal limit was not observed in most patients during early CsA administration, and at the end of the follow-up all the patients had a normal SCr. Relapse occurred in 33.3% of the patients after withdrawing CsA for 4 - 24 months. No chronic CsA renal toxicity was observed in 4 patients who had a repeat renal biopsy after CsA treatment for 6 - 24 months.</p><p><b>CONCLUSIONS</b>CsA could be regarded as an effective therapy for patients with membranous lupus nephropathy, but its adverse effects, especially its nephrotoxicity, should be carefully monitored during CsA treatment.</p>

Genetic variation of mannose-binding protein associated with glomerular immune deposition in IgA nephropathy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the relationship between codon 54 gene polymorphism of the host defense molecule, mannose-binding protein (MBP), and the patterns of glomerular immune deposition in IgA nephropathy (IgAN).</p><p><b>METHODS</b>IgAN patients with different patterns of glomerular immune deposition were selected and divided into two groups. Group A consisted of 77 patients with glomerular IgA and C3 deposits, and Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. Clinical features and laboratory relevant data of all patients were collected. One-hundred and forty healthy adults were recruited as normal controls. The MBP gene codon 54 GGC/GAC polymorphism was investigated by using polymerase chain reaction and restriction fragment length polymorphism.</p><p><b>RESULTS</b>The genotype frequency of GGC/GAC heterozygotes was significantly higher in Group AGM as compared with that of Group A (41.4% vs 19.5%, P < 0.01) or normal subjects (41.4% vs. 26.4%, P < 0.05), while no difference was found in the distribution of MBP genotypes between Group A and normal subjects. GAC allele frequency was also higher in Group AGM than that in Group A (0.24 vs. 0.14, P < 0.05) or normal subjects (0.24 vs. 0.15, P < 0.05). The variant allele (GAC) was markedly associated with Group AGM (OR = 1.95, 95% CI: 1.06 - 3.58). In both Group A and Group AGM, more patients carrying the variant allele had episodes of upper respiratory or gastrointestinal infections prior to the onset of IgAN than those with wild homozygotes (GGC/GGC).</p><p><b>CONCLUSIONS</b>Genetic variation of the host defense molecule, MBP, may be involved in the formation of the diverse patterns of glomerular immune deposition in IgAN. The variant allele of the MBP gene may partially account for abundant immune deposits in some IgAN patients.</p>

Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment.</p><p><b>METHODS</b>Twelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed.</p><p><b>RESULTS</b>Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN.</p><p><b>CONCLUSIONS</b>The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.</p>

Genetic variations in plasminogen activator inhibitor-1 gene and beta fibrinogen gene associated with glomerular microthrombosis in lupus nephritis and the gene dosage effect / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship of plasminogen activator inhibitor-1 (PAI-1) gene -675 4G/5G and beta fibrinogen gene -455 G/A variations to glomerular microthrombosis(T) in lupus nephritis(LN).</p><p><b>METHODS</b>One hundred and one patients with biopsy proven LN were divided into two groups according to the presence or absence of glomerular microthrombus, i.e. group LN+T(n=46) and group LN-T(n=55). The genotypes of PAI-1 gene and beta fibrinogen gene were profiled by polymerase chain reaction-sequence length polymorphism (PCR-SLP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. Clinical baseline data at the time of renal biopsy were collected. Normal controls consisted of 128 unrelated healthy adults. The etiologic fractions (EF) were calculated for estimating the contribution of risk genotypes of the two candidate genes to an increase in susceptibility to glomerular microthrombosis in LN patients.</p><p><b>RESULTS</b>Both the 4G/4G genotype and the 4G allele of PAI-1 gene occurred more frequently in group LN+T (47.83% and 0.685) than in group LN-T (23.64% and 0.507)(P<0.05) and normal controls (28.13% and 0.570) (P<0.05). The PAI-1 4G/4G genotype was significantly associated with microthrombosis (OR=2.96, 95%CI:1.26-6.92). Besides, the prevalence of the genotypes carrying the A allele of beta fibrinogen gene, i.e. G/A and A/A, as well as the prevalence of the A allele per se, was increased in group LN+T (47.83% and 0.261) versus group LN-T (27.27% and 0.145)(P<0.05). LN patients carrying the A allele had a high risk of glomerular thrombosis(OR=2.44, 95%CI:0.98-5.59). In addition, the presence of the PAI-1 4G/4G genotype together with the A allele of the beta fibrinogen gene was found to be a greater risk factor (OR=4.5, 95%CI: 1.34-15.12) for glomerular thrombosis in LN than the 4G/4G genotype or the A allele alone. The pooled EF (45.98%) for the risk genotypes of both PAI-1 gene and beta fibrinogen gene was also higher than that for the risk genotypes of either gene (31.67% and 28.23%).</p><p><b>CONCLUSION</b>The above findings indicated that genetic variations in PAI-1 and beta fibrinogen loci might represent risk factors for glomerular microthrombosis in LN. They may have synergetic impact and present gene dosage effect on the susceptibility to this pathological subphenotype.</p>

The relationship between renal histology,its mechanism and the treatment of Lupus nephutis / 中国实用内科杂志

This paper emphasizes the importance of the mechanism of renal tissue damage in conducting treatment of lupus nephritis in addition to the renal histology.There are at least 4 kinds of mechanisms related to the renal tissue damage of LN including circulating immune complex deposition,in situ immune complex formation,vasculitic change and thrombotic mircoangiopathy.Treatment according to the mechanisms of tissue damage will give rise to a much better result as compared with the classic treatment based on morphology alone.Multi-target immune theapy has been recommended for treatment of those severe and complicated LN.

Effects of mycophenolate mofetil on patients with pauci-immune crescentic glomerulonephritis / 中国实用内科杂志

Objective To compare the effect,relapse rate and outcomes between mycophenolate mofetil(MMF)and pulse intravenous cyclophosphamide(CTX)in the induction therapy of pauci-immune crescentic glomerulonephritis(PICGN)in Chinese.Methods A total of 44 patients who had PICGN[16 male,28 female,age(46.8?13.7)y],of whom 25 patients were ANCA positive,were enrolled in this study.All patients had renal involvement with ≥50% crescent formation prior to the study and received either MMF treatment(MMF group,n=22)or intermittent CTX pulse therapy(CTX group,n=22).The patients in both groups also received methylprednisolone(MP)pulse therapy followed by oral prednisone.General conditions,clinicopathological findings,remission rate,relapse rate,and outcomes were compared.All the patients were followed up until June 2005,with an average follow-up of 8～60(Med 27)months in the MMF group,and 6～72(Med 29)months in the CTX group.Results No significant difference was found between MMF group and CTX group in general conditions,base parameters of clinical and pathological findings.The remission rate at the 12th month in MMF and CTX group was 90.9% and 72.7% respectively.The complete remission rate in MMF group(59.1%)was significantly higher than that of the CTX group(27.3%)(P

Eosinophil infiltration and peritubular capillary C4d deposition in acute renal allograft rejection / 中国免疫学杂志

Objective:To study the correlation between deposition of C4d along peritubular capillaries (PTC) and interstitial eosinophilic infiltration in renal allografts.Methods:Deposition of C4d in kidneys was assayed by indirect immunoflourescence of the renal allograft biopsies.Twenty-six patients were demonstrated strongly diffuse staining of PTC,who were defined as C4d+ group,while the biopsies of thirty patients with acute rejection exhibited negative for PTC C4d staining served as the controls,who were defined as C4d-group.Eosinophils were counted under microscope.Results:The C4d+group was demonstrated significantly greater interstitial eosinophilic infiltration than did the C4d-group(P

Therapeutic window of whole blood rapamycin concentration in recipients of renal transplantation / 中华肾脏病杂志

Objective To study the therapeutic window of rapamycin(RPM) concentration in primary recipients of renal transplantation. Methods An open label, multi center study was performed. One hundred primary renal allograft recipients with cadaveric donors were enrolled from 4 transplantation centers in China. The immunosuppressive regimen was triple therapy,i.e.RPM combined with CsA and steroid. A loading dose of RPM 6 mg/d was administered within 48 hours after transplantation, then a maintaining dose of 2 mg/d was administered. The whole blood concentration of RPM was measured by HPLC method. Results The whole blood concentration of RPM in this group was (6.65?2.75)ng/ml, the 10th and 90th percentile for RPM concentration was 3 2 ng/ml and 10 26 ng/ml,respectively.9 5%(8/84)patients suffered from acute rejection during the 6 month period after transplantation in this study, and the concentration of RPM in these was lower than that in non rejection patients(P=0.001). Hyperlipidemia and liver dysfunction were the most frequently adverse events, and RPM concentration was significantly associated with the concentration of triglyceride. Conclusions 4～8 ng/ml is a suitable level for RPM concentration. Regular drug monitoring and reasonable dose modulation may increase the validity and security of RPM.

The titer of ANCA in relation to disease activity in patients with microscopic potyarteritis / 中华肾脏病杂志

Objective To study whether ANCA liter is sensitive serological marker reflecting vasculitis disease activity. Methods MPO-ANCA and IF-ANCA tilers variation in five sera specimen with active MPA diseases were studied after methylprednisolone and cyclophosphamide pulse therapy. The clinical and pathological features of 5 patients with MPA were investigeted comparing pre-treatment with post-treatment. Results (1) Serum ANCA were found positive and increased liter in 5 patients wilh active MPA disease. (2) Titer decreased after Ireatment, while renal function improved. (3) After half year, MPO-ANCA was negative in 5 patients, IF-ANCA was negative in 2 patients. Conclusion There is a close correlation between serum ANCA titer and MPA renal disease activity.

The clinical and pathological features of drug-associated acute interstitial nephritis / 中华肾脏病杂志

Objective To evaluate the clinical and pathological features of drug-associated acute interstitial nephritis. Methods Clinical presentations and pathological features were investigated in 14 patients with drug-associated acute interstitial nephritis. Lymphocyt; stimulation test was performed to confirm, the offending drugs. Results All patients presented with acute renal failure, but typical clinical features were often absent. Renal biopsy was therefore needed to establish the diagnosis. Conclusion Lymphocyte stimulation test is a very useful means in the determination of offending drugs.