Nephrotic syndrome (NS) is a kidney disease characterized by hypertriglyceridemia, massive proteinuria, hypo-albuminemia and peripheral edema. Sinkihwan-gamibang (SKHGMB) was recorded in a traditional Chinese medical book named "Bangyakhappyeon ()" and its three prescriptions Sinkihwan, Geumgwe-sinkihwan, and Jesaeng-sinkihwan belong to Gamibang. This study confirmed the effect of SKHGMB on renal dysfunction in an NS model induced by puromycin aminonucleoside (PAN). The experimental NS model was induced in male Sprague Dawley (SD) rats through injection of PAN (50 mg·kg^-1)via the femoral vein. SKHGMB not only reduced the size of the kidneys increased due to PAN-induced NS, but also decreased proteinuria and ascites. In addition, SKHGMB significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen. SKHGMB relieved glomeruli dilation and tubules fibrosis in the glomeruli of the NS model. SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome including NLRP3, ASC, and pro-caspase-1 in NS rats. SKHGMB reduced the protein and mRNA levels of fibrosis regulators in NS rats. The results indicated that SKHGMB exerts protective effects against renal dysfunction by inhibiting of renal inflammation and fibrosis in NS rats.
Animals ; Kidney ; Male ; Nephrotic Syndrome/drug therapy* ; Proteinuria/metabolism* ; Puromycin Aminonucleoside/toxicity* ; Rats ; Rats, Sprague-Dawley

OBJECTIVES: To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia. METHODS: A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels. RESULTS: Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage ( CONCLUSIONS Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.
Adipokines ; Chemokines ; Child ; Cytokines/metabolism* ; GPI-Linked Proteins/metabolism* ; Humans ; Hyperlipidemias ; Lectins/metabolism* ; Lipids ; Nephrotic Syndrome/drug therapy* ; Proteinuria

OBJECTIVETo investigate the effects of rituximab (RTX) in children with steroid-dependent nephrotic syndrome.

METHODFive cases of children with steroid-dependent nephrotic syndrome seen from May 2012 to February 2013 in whom only steroid plus calcineurin inhibitor was effective and the disease recurred on reduction of dose were enrolled into this study, including 3 males and 2 females. Calcineurin inhibitors were stopped and steroids was changed to full dose. After the general condition improved, RTX was given at a dose of 375 mg/m(2), once a week for a total of three times for one course. After urine protein became negative for five days, the dose of steroid was changed to 2 mg/kg every other day, thereafter the dose was reduced by 5 mg per every 2 weeks, until discontinuation. After regular monitoring, when peripheral blood B cells were ≥ 3%, a second RTX was added.

RESULTUrine protein was negative in 2-7 days in 5 patients after the first RTX treatment. Before treatment B lymphocytes in peripheral blood was 7.8% to 13.0% and after the first course of RTX treatment decreased to 0 in the first 6 to 8 months at the beginning of recovery, while in the first 7 to 10 months to 3.3%-6.1%, after a second RTX was given, B lymphocytes were reduced to 0, but in two cases (cases 1 and 3) B lymphocytes rose again at 16 and 17 months, in the first 17 and 18 months rose to 4.16% and 4.17%, RTX was given once again respectively. B lymphocytes were reduced to 0 again. Currently the 5 patients continued to be negative for urine protein, maintaining remission for 12 to 20 months.RTX infusion had no significant side effects, and side effects of steroid and calcineurin inhibitor disappeared.

CONCLUSIONIn children with steroid-dependent and only calcineurin inhibitor effective nephritic syndrome, relapse may still occur after improvement of nephrotic syndrome, after the first RTX treatment, regular monitoring of B lymphocytes, RTX supplementary treatment in advance can help discontinuation of steroids and immunosuppressive agents and maintain remission.

Anti-Inflammatory Agents ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; therapeutic use ; Antigens, CD19 ; metabolism ; B-Lymphocytes ; drug effects ; metabolism ; Calcineurin Inhibitors ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lymphocyte Count ; Male ; Nephrotic Syndrome ; drug therapy ; metabolism ; Proteinuria ; urine ; Recurrence ; Remission Induction ; Rituximab ; Treatment Outcome

Alkyl and Aryl Transferases ; genetics ; Child ; DNA, Mitochondrial ; genetics ; Fibroblasts ; metabolism ; Glomerulosclerosis, Focal Segmental ; diagnosis ; drug therapy ; genetics ; Humans ; Kidney Diseases ; diagnosis ; drug therapy ; genetics ; Mitochondrial Diseases ; diagnosis ; drug therapy ; genetics ; Mutation ; Nephrotic Syndrome ; diagnosis ; drug therapy ; genetics ; Protein Kinases ; genetics ; Ubiquinone ; analogs & derivatives ; biosynthesis ; deficiency ; therapeutic use

OBJECTIVETo study the characteristics of clinicopathology and prognosis of 3 pediatric cases diagnosed as C3 glomerulopathy, and to improve the understanding of C3 glomerulopathy in children.

METHODThe medical record, plasma complement C3, Factor H (FH) and its autoantibody, and therapeutic response of the 3 cases were analyzed, and their prognosis were followed up.

RESULTOf the 3 cases, 2 were male and 1 was female, the age of onset was 9 years, 12 years, 5 years 4 months, the duration from onset to renal biopsy was 3 months, 7 months and 20 days, and the follow-up period were 2.6 years, 8 months and 1.5 years respectively.

CLINICAL MANIFESTATIONSAll the 3 cases showed microscopic hematuria, with or without gross hematuria and proteinuria. Two showed persistently decreased plasma complement C3, in the other one C3 was in normal lower limit, all presented with decreased FH concertration, in 1 case anti-FH antibody was positive. Their clinical diagnosis was post-streptococcal glomerulonephritis, nephrotic syndrome (NS) nephritis type, and mesangial proliferative glomerulonephritis respectively.

PATHOLOGICAL FINDINGSAll showed evident deposition of C3 on glomerular basement membrance (GBM) and mesangial region by immunofluorescence (IF) and electron dense deposit in GBM, mesangial region or para-mesangial region by Electron microscopic (EM) examination Treatment and prognosis: The case with NS showed no response to steroid, so steroid was gradually stopped after renal biopsy and replaced by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonist (ARB). The other two cases were treated with ACEI and renal protective treatment. Of the 3 cases, one gradually showed elevated serum creatinine (Scr) and decreased creatinine clearance rate (Ccr), the other two were normal, but slightly increased indications for early kidney injury.

CONCLUSIONC3 glomerulopathy is characterized by evident C3 deposition under IF. Its clinical and pathological manifestations vary a lot. The decreased plasma C3 and FH suggest that the abnormal regulation of complement system play an importment role in its pathogenesis.

Angiotensin Receptor Antagonists ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Child ; Child, Preschool ; Complement C3 ; metabolism ; Complement Factor H ; deficiency ; metabolism ; Female ; Fluorescent Antibody Technique ; Glomerulonephritis ; complications ; drug therapy ; metabolism ; pathology ; Hematuria ; etiology ; pathology ; Humans ; Kidney Glomerulus ; metabolism ; pathology ; Male ; Nephrotic Syndrome ; etiology ; pathology ; Proteinuria ; etiology ; pathology

OBJECTIVETo examine serum concentration of interleukin-18 (IL-18) and IL-18 mRNA expression in peripheral blood mononuclear cells (PBMCs) in children with primary nephrotic syndrome (PNS) and explore the possible role of IL-18 in steroid-resistant nephrotic syndrome (SRNS).

METHODSSixty-six children with newly diagnosed PNS, including 39 cases of steroid sensitive nephrotic syndrome (SSNS) and 27 cases of SRNS, were enrolled. Forty healthy children were used as a normal control group. Blood samples were collected before and 8 weeks after glucocorticoid treatment. Serum concentration of IL-18 was measured using ELISA. IL-18 mRNA expression in PBMCs was detected by the RT-PCR method. The amount of 24-hr urine protein was measured by the biuret method. Serum contents of total cholesterol (T-Ch), triglyceride (TG), low density lipoprotein (LDL), total protein (TP), and albumin (Alb) were measured by the automatic biochemistry analyzer.

RESULTSSerum concentration of IL-18 and IL-18 mRNA expression in PBMCs in the SSNS and the SRNS groups were significantly higher than those in the normal control group before treatment (P< 0.05). The SRNS group had increased serum protein concentration of IL-18 and IL-18 mRNA expression in PBMCs compared with the SSNS group before treatment (P< 0.05). Serum LDL content in the SRNS group was also significantly higher than that in the SSNS group before treatment (P< 0.05). After treatment, serum concentration of IL-18 and IL-18 mRNA expression in PBMCs in the SRNS group were significantly higher than those in the SSNS and the normal control groups (P< 0.05). Serum concentration of IL-18 and IL-18 mRNA expression in PBMCs in the SSNS group were significantly reduced after treatment, but the alterations of IL-18 were not observed in the SRNS group after treatment.

CONCLUSIONSSRNS was associated with increased serum IL-18 concentration and IL-18 mRNA expression in PBMCs. Over-production of IL-18 may play a role in the development of SRNS.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Child ; Child, Preschool ; Drug Resistance ; Female ; Humans ; Interleukin-18 ; blood ; genetics ; physiology ; Leukocytes, Mononuclear ; metabolism ; Lipoproteins, LDL ; blood ; Male ; Nephrotic Syndrome ; blood ; drug therapy ; RNA, Messenger ; blood

OBJECTIVETo study the effect of triptergium wilfordii polyglycosidium on the content of Th1 and Th2 in the treatment child patients of rcurrent nephrotic syndrome.

METHODPatients were randomized into treatment group and health group. Sixty-one patients in treatment group were treated with triptergium wilfordii polyglycosidium 1 mg x kg(-1) x d(-1) orally tid for 12 weeks. However, patients in health group was not treated with any drugs. Twelve weeks constituted one course of treatment and the content of IL-12, IL-2, TNF-alpha, IL-13, IL-6, IL-4 in peripheral blood was measured before and behind therapy.

RESULTIn treatment group, the content of serum cytokines behind therapy was significantly lower than that before therapy, except for IL-12.

CONCLUSIONTriptergium wilfordii polyglycosidium could reduce the cytokine level (except for IL-12) of Th1 and Th2, which could lead a therapeutic effect of in the child patients of RNS.

Child ; Drugs, Chinese Herbal ; pharmacology ; Female ; Glycosides ; pharmacology ; Humans ; Interleukin-12 ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Male ; Nephrotic Syndrome ; drug therapy ; metabolism ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism ; Tripterygium ; chemistry ; Tumor Necrosis Factor-alpha ; metabolism

Child ; Child, Preschool ; Female ; Humans ; Kidney ; metabolism ; Male ; NF-kappa B ; antagonists & inhibitors ; metabolism ; Nephrotic Syndrome ; drug therapy ; metabolism ; Proteinuria ; metabolism

OBJECTIVE: To investigate the difference of Pax2 and P53 expressions in children with primary nephritic syndrome (PNS) and the effect of Pax2 on glucocorsteroid (GC)-resistance. METHODS: Renal Pax2 and P53 expressions in children with PNS (40 patients) were detected by immunohistochemistry. A semiquantitative score was used to evaluate the injury degree of the glomeruli and the tubulointerstitium, and correlation analysis was done among Pax2, P53 and pathologic score. RESULTS: Pax2 and P53 expressions were not found in the control group. Pax2 expression of renal tubule epithelia exsisted in children with PNS and there was weak or no expression of Pax2 in the podocytes. Pax2 expressions in the proximal tubule and the distal tubule in the GC-resistant group were more intense than those in the GC-intensive group (P <0.01). The more the Pax2 expression in the tubule, the more abnormal structure such as dilation and atrophy. Pax2 expression in the tubule epithelia was positively correlated with pathologic score of tubulointerstitium (P < 0.01). There was no P53 expression in the GC-intensive group, but there exsisted P53 expression in parts of the patients from the GC-resistant group, mainly distributing in the renal tubular epithelia. P53 expression was positively correlated with P53 expression and the pathologic score of tubulointerstitium (P < 0.01). CONCLUSION Over-expression of Pax2 in the renal tubule epithelia may improve P53 expression to a certain degree, which may aggravate the lesion of the renal tubule. It may be one of the mechanisms resulting in GC-resistant in children with PNS.
Adolescent ; Child ; Child, Preschool ; Drug Resistance ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Male ; Nephrotic Syndrome ; drug therapy ; metabolism ; PAX2 Transcription Factor ; biosynthesis ; genetics ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

OBJECTIVEPrimary nephrotic syndrome (PNS) is one of the common renal diseases in children, the pathogenesis of which is unclear. Evidences suggested that the proteinuria of NS is associated with the increased expression of the interleukin-8 (IL-8) genes. The purpose of the study was to evaluate the serum concentration and mRNA expression of IL-8 before and after the methylprednisolone pulse therapy (MPT) in PNS.

METHODThirty children with PNS diagnosed from December 2000 to October 2001 were enrolled in this study (patients group). They were not treated with glucocorticoid at least within the recent 3 months. The children aged from 1.5 to 14 years (mean 8.5 years), and included 24 boys and 6 girls. Eighteen healthy children were selected as control group after physical examination. The children in control group aged from 2 to 14 years (mean 8 years) and included 13 boys and 5 girls. All patients were treated with MPT intravenously (30 mg/kg) for successive 3 days followed by oral prednisone. The serum protein level of IL-8 was measured by ELISA according to the manufacturer's instructions. Human IL-8 ELISA kit was purchased from Jingmei corporation Shenzhen, China. And the concentration was obtained after drawing the standard curve. The expression of IL-8 gene was detected with RT-PCR method. The important reverse transcription reagent kit and Trizol reagent were all bought from GIBCO BRL, USA. Statistical analysis of rank sum test was adopted for data processing.

RESULTSComparison of the serum IL-8 level in the same patient before and after the therapy showed significant difference [29.59 (7.14-352.08) ng/L vs. 10.80 (4.27-77.86) ng/L, u = 4.26, P < 0.01]. The serum level in patient group before the therapy increased obviously in comparison to the level of the control group [10.37 (5.46-33.31) ng/L, u = 4.53 P < 0.01]. The serum level of IL-8 in patient group after the therapy also showed significant difference compared to the control group (u = 2.73 P < 0.01). The mRNA expression of IL-8 in the same patient before and after therapy showed significant difference [0.862 (0.776-0.95) vs. 0 (0-0.754), u = 3.902 P < 0.01].

CONCLUSIONIL-8 may be involved in the pathogenesis of PNS because of the significant increase of the serum IL-8 level and PBMC IL-8 mRNA expression in nephrotic syndrome children. Methylprednisolone pulse therapy in PNS was able to inhibit the protein production and PBMC mRNA expression of IL-8, so the therapeutic mechanism of MPT in PNS might be associated with the inhibition of IL-8 expression.

Adolescent ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Expression ; drug effects ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infusions, Intravenous ; Interleukin-8 ; blood ; genetics ; Male ; Methylprednisolone ; administration & dosage ; therapeutic use ; Nephrotic Syndrome ; drug therapy ; Pulse Therapy, Drug ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Treatment Outcome