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BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.
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OBJECTIVE: To discuss expression of antiphospholipid antibody subtypes in primary glomerular diseases. METHODS: All1021 cases who were admitted to our center between June 2015 and July 2017 in Kidney Disease Center, First Affiliated Hospital,College of Medicine, Zhejiang Universityhad renal biopsy in our center and they were praved to have primary glomerular diseases(303 cases of membranous nephropathy, 483 cases of IgA nephropathy, 76 cases of mesangial proliferative glomerulonephritis, 119 cases of minimal change nephropathy and 40 cases of focal segmental glomerulosclerosis). The levels of anti-cardiolipin(ACL) antibody subtypes(IgG, IgM and IgA)and anti-β2 glycoprotein 1(β2 GP1) antibody subtypes(IgG, IgM and IgA) were measured and compared.RESULTS: The positive rate of APA in membranous nephropathy group was highest(17.5%) and in minimal change nephropathy was lowest group(11.8%), but there were no significant differences among the groups. The positive rates of ACL in IgA nephropathy and mesangial proliferative glomerulonephritis were 11.4% and 14.5% respectively, which were significantly higher than those of anti-β2 GP1 antibody(P< 0.001, P = 0.009 respectively). The positive rate of anti-β2 GP1 antibody in membranous nephropathy group was 11.2%,significantly higher than that in the other four groups. The positive rate of ACL-IgM in mesangial proliferative glomerulonephritis group was 13.2%, which was significantly higher than that in the other four groups(P< 0.05). The positive rate of ACL-IgA in IgA nephropathy group was 5.8%, which was significantly higher than the other four groups, and there was no statistical difference(P<0.05).CONCLUSION: Antiphospholipid antibody is positive in patients with primary glomerular diseases, and the positive rate of its subtypes varies among the different pathological types of glomerulonephritis, which can be helpful to differential diagnosis and treatment of the disease.
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Primary glomerulonephritis (PGN) remains the major cause of end-stage renal disease (ESRD) in our country. The histologic entity of PGN mainly includes immunoglobulin A nephropathy (IgAN), idiopathic membranous nephropathy (IMN), minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN). The pathogenesis of PGN is correlated with renal immune complex deposition, podocyte injury, infection and abnormal regulation of complement system. Nowadays PGN is short of specific treatments, the main therapeutic methods of PGN consists of renin angiotensin aldosterone system (RAAS) inhibitor, corticosteroids, cytotoxic drugs, lipid-lowering agents, anticoagulant therapy and antiplatelet adhesion. Patients who are drug-resistant or intolerance of the side effects will have a poor prognosis. Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody. The binding of RTX to CD20 on the cell membrane of B lymphocytes leads to significant depletion of peripheral B lymphocytes, which plays an immunosuppressive role. Rituximab is originally approved for the treatment of lymphoma, after that there was growing evidence showed RTX was effective in part of immunological diseases, including systemic lupus erythematosus and anitneutrophil cytoplasmic antibody associated vasculitis. As a result, whether RTX will act as an effective treatment modality in PGN has aroused extensive attention. In recently years, clinical researches concerning RTX used for the treatment of PGN have been published in succession. This paper reviewed clinical studies focused on the use of rituximab in the treatment of IMN, MCD, FSGS and IgAN.
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Primary glomerulonephritis (PGN) remains the major cause of end-stage renal disease (ESRD) in our country. The histologic entity of PGN mainly includes immunoglobulin A nephropathy (IgAN), idiopathic membranous nephropathy (IMN), minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN). The pathogenesis of PGN is correlated with renal immune complex deposition, podocyte injury, infection and abnormal regulation of complement system. Nowadays PGN is short of specific treatments, the main therapeutic methods of PGN consists of renin angiotensin aldosterone system (RAAS) inhibitor, corticosteroids, cytotoxic drugs, lipid-lowering agents, anticoagulant therapy and antiplatelet adhesion. Patients who are drug-resistant or intolerance of the side effects will have a poor prognosis. Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody. The binding of RTX to CD20 on the cell membrane of B lymphocytes leads to significant depletion of peripheral B lymphocytes, which plays an immunosuppressive role. Rituximab is originally approved for the treatment of lymphoma, after that there was growing evidence showed RTX was effective in part of immunological diseases, including systemic lupus erythematosus and anitneutrophil cytoplasmic antibody associated vasculitis. As a result, whether RTX will act as an effective treatment modality in PGN has aroused extensive attention. In recently years, clinical researches concerning RTX used for the treatment of PGN have been published in succession. This paper reviewed clinical studies focused on the use of rituximab in the treatment of IMN, MCD, FSGS and IgAN.
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Abtract:Purpose To analyze epidemiological characteristics and pathological types of 1 645 renal biopsies in Jiangsu province. Methods The reports of 1 654 percutaneous renal biopsies performed from January 2009 to June 2013 were retrospectively analysed . Results 1 597 out of 1 645 renal patients were successfully biopsied with a success rate of 97. 1%. Primary glomerular diseases ac-counted for 78. 56% of the total patients, secondary glomerular diseases 18. 71%. IgA nephropathy and mesangial proliferative lession accounted for high percent of primary glomerular diseases. Lupus nephritis was the most frequent pathologic type of secondary glomeru-lar diseases, followed by allergic purpura nephritis and diabetic nephropathy. Mesangial proliferative glomerulonephritis and hyperten-sive renal injury were more common in the Southern than in the Northern Jiangsu province, while acute tubular necrosis and allergic purpura nephritis were less in the Southern Jiangsu province. Conclusions Primary glomerular disease is still the most frequent glo-merular diseases in Jiangsu province, among which the IgA nephropathy was predominated. In secondary glomerular disease, lupus ne-phritis is the most frequent pathological type. The incidences of kidney diseases have geographical variation.
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Deregulation of soluble apoptosis stimulating fragment (sFas) plays an important role in glomerulonephritis (GN). The study assed the influence of immunosuppressive treatment on serum and urine sFas in patients with proliferative (PGN) and non-proliferative (NPGN) GN, and evaluated the potential of sFas measurements in predicting outcomes. Eighty-four patients with GN (45 males and 39 females) were included. Serum concentration (ng/mL) and urinary excretion (ng/mg of urinary creatinine) of sFas were measured before and after the treatment. After 12 months of therapy with steroids and cyclophosphamide, patients were divided into two subgroups according to the treatment results: Responders (R) and Non-Responders (NR). The sFas urinary excretion was reduced after treatment in both PGN and NPGN (from 17.12 +/- 15 to 5.3 +/- 4.2, P = 0.008 and from 10.11 +/- 6.1 to 3.4 +/- 3.0, P = 0.039; respectively) whereas the sFas serum concentration remained unchanged. In PGN, pre-treatment urinary sFas concentration was significantly lower in the Responders than in Non-Responders (2.3 +/- 3.1 vs 19.4 +/- 14.1, P = 0.003), and was lower still than in both R (P = 0.044) and NR (P = 0.042) subgroups with NPGN. The immunosuppressive treatment reduced sFas urinary excretion in proliferative and non-proliferative GN and results suggest that the lower urinary sFas may be linked with favorable therapy outcomes in patients with PGN.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , fas Receptor/blood , Cyclophosphamide/therapeutic use , Glomerulonephritis/drug therapy , Immunosuppressive Agents/therapeutic use , Steroids/therapeutic use , Treatment OutcomeABSTRACT
Interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptors (sTNF-R) type I and II, and regulated upon activation, normal T-cell expressed and secreted (RANTES) play an important role in the modulation of primary glomerulonephritis (GN) course. The aim of the study was to assess whether pre-treatment measurements of IL-1ra, sTNF-R, and RANTES assessed conjointly may be useful as predicting factors in patients with GN. In 84 patients (45 males and 39 female) serum concentration (pg/mL) and urinary excretion (pg/mgCr) of cytokines were measured. After 12 months of therapy with steroids and cyclophosphamide the patients were divided into two subgroups: Responders (R) and Non-Responders (NR) according to the treatment results. The urinary IL-1ra, TNF-RI and RII were significantly higher in R than NR (1,732 vs 646 with P < 0.001, 13.1 vs 6.3 with P = 0.005, and 33.6 vs 14.4 with P = 0.012). The urinary RANTES excretion was increased in NR (79.6 vs 28.5; P < 0.001). The multivariable analysis showed that if conjointly assessed, only urinary IL-1ra, TNF-R I and R II, RANTES with 85% probability pointed the feature remission (R). In conclusion, the urinary excretion of IL-1ra, TNF-R I and R II, and RANTES examined conjointly are effective in predicting favorable response to immunosuppressive treatment in patients with GN.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Cyclophosphamide/therapeutic use , Glomerulonephritis/drug therapy , Immunosuppressive Agents/therapeutic use , Interleukin 1 Receptor Antagonist Protein/analysis , Lymphocyte Activation , Multivariate Analysis , Predictive Value of Tests , Receptors, Tumor Necrosis Factor, Type I/analysis , Receptors, Tumor Necrosis Factor, Type II/analysis , Steroids/therapeutic use , T-Lymphocytes/immunologyABSTRACT
Objective To investigate the state of glucocorticoid(GC) - induced osteoporosis (GIOP) and the current prevention of GIOP in patients with primary glomerulonephritis. Methods Primary glomerulonephritis patients receiving GC therapy were observed and bone mineral density (BMD) in the lumbar spine and the femoral neck were measured. Age, sex, body - mass - index, smoking history, the time and accumulative dose of GC treatment, and the state of osteoporosis prevention were investigated, the factors that influence the BMD were analyzed. Results A total of one hundred and twenty- three patients were included in this study. Among them, osteoporosis and os-teopenia were found in 82 patients (66.7%). Lumbar spine BMD decrease gradually with the increase of the accumulative dose of GC. There were statistical differences in the BMD of lumbar spine in patients with receving GC at the period of less than 1 month compared with other groups( 1-12 months) (P
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BACKGOUND: Recently it has been reported that several cytokine gene polymorphisms regulate cytokine production and play an important role in immune and inflammatory response. We evaluated IL-1beta IL-1Ra, and TNF-alpha gene polymorphism in patients with primary glomerulonephritis to determine the association between cytokine polymorphism and disease susceptibility. METHODS: In this study, we enrolled 118 patients with primary glomerulonephritis and healthy 300 persons who had visited the health screening center. We analyzed -511C/T polymorphism of IL-1beta tandem repeats polymorphism in intron 2 of IL-1Ra and -308G/A polymorphism of TNF-alpha We classified primary glomerulonephritis according to pathologic finding and clinical diagnosis. RESULTS: There were no differences with IL-1betaand TNF-alpha gene polymorphism between patient and control group. The carriage of IL1RN*2 was significantly associated with an increased risk of primary glomerulonephritis (patients:control=12.75:5.4%, p<0.01). IL1RN*2 was significantly frequent in patients with membranous GN or minimal change disease (p<0.05). When we classified glomerulonephritis according to clinical diagnosis, IL1RN*2 carriage rate was higher in patients with nephrotic syndrome and RPGN or acute nephritic syndrome than patients with asymptomatic urinary abnormalities (p<0.05). IL-1beta(TT) genotype was more prevalent in acute glomerulonephritis (68.4%) than asymptomatic urinary abnormalities or other glomerulonephritis. TNF2 carriage rate showed a lower tendency in patients with asymptomatic urinary abnormalities. CONCLUSION: IL1RN*2 is significantly associated with an increased risk of development of primary glomerulonephritis. We suggest cytokine gene polymorphism is also related to clinical manifestations of glumerulonephritis.
Subject(s)
Humans , Diagnosis , Disease Susceptibility , Genotype , Glomerulonephritis , Interleukin 1 Receptor Antagonist Protein , Introns , Mass Screening , Nephrosis, Lipoid , Nephrotic Syndrome , Tandem Repeat Sequences , Tumor Necrosis Factor-alphaABSTRACT
To determine the relationship between the urinary endothelin (ET-1), nitric oxide (NO) levels and the clinical, pathologic types of primary glomerulonephritis (GN) patients, urinary levels of ET-1 and NO were detected in 27 patients with biopsy-proven primary GN and 12 normal controls by radioimmunoassay and by copper-plated and cadmium column reduction assay, respectively. The results showed that urinary ET-1 levels in the patients with primary GN were significantly higher than in normal controls (p < 0.01), while the urinary ET-1 levels in patients with moderate mesangial proliferation GN were significantly higher than those in patients with mild mesangial proliferation GN (p < 0.05). Urinary ET-1 levels in patients whose clinical feature was nephrotic syndrome were found to be higher than in patients whose clinical feature was nephritic syndrome. However, urinary NO levels were to the contrary (p < 0.05). The ratio of ET-1/NO in primary GN patients was significantly higher than that in normal controls, and it positively correlated with the 24-hour urinary excretion of protein. These results suggest that urinary ET-1 levels are related to the proliferation of mesangial cells. The imbalance between ET-1 and NO may be related to the pathogenesis of primary GN and the occurrence of proteinuria.
Subject(s)
Adult , Female , Humans , Male , Adolescent , Endothelin-1/urine , Endothelin-1/physiology , Glomerulonephritis/urine , Glomerulonephritis/etiology , Middle Aged , Nitric Oxide/urine , Nitric Oxide/physiology , Nitric Oxide Synthase/metabolismABSTRACT
Objective To study the expression of interleukin-13(IL-13) in renal tissues of several common pathologic types of primary glomerulonephritis(PGN).Methods Immunohistochemistry was used to examine the expression of IL-13 in renal tissues of 81 patients with PGN and 10 normal control cases.The correlation analysis was performed with biochemical and pathological indicators.Results Extensive expression of IL-13 was found in renal tissues of patients with PGN.The expression of IL-13 in renal tissues was positively correlated with the concentration of blood urea nitrogen,serum creatinine,the quantitation of urine protein and the crescent formation in glomerular(r=0.325,0.275,0.291,0.231,respectively).It was negatively correlated with glomerular filtration rate and serum albumin(r=-0.448,-0.296,respectively).Conclusion IL-13 participates in the process of inflammation reaction and crescent formation in the renal tissues in patients with PGN,and is correlated with the progression of renal function and the level of urea protein.