1.Sinkihwan-gamibang ameliorates puromycin aminonucleoside-induced nephrotic syndrome.
Hyeon Kyoung LEE ; Youn Jae JANG ; Se Won NA ; Hye Yoom KIM ; Byung Hyuk HAN ; Yun Jung LEE ; Ho Sub LEE ; Jung Joo YOON ; Dae Gill KANG
Chinese Journal of Natural Medicines (English Ed.) 2022;20(3):177-184
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
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Kidney
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Male
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Nephrotic Syndrome/drug therapy*
;
Proteinuria/metabolism*
;
Puromycin Aminonucleoside/toxicity*
;
Rats
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Rats, Sprague-Dawley
2.Expression of adipokines in children with primary nephrotic syndrome and its association with hyperlipidemia.
Ru-Xin ZHANG ; Xuan ZHANG ; Bi-Li ZHANG ; Zhu-Feng LIU ; Shu-Xiang LIN
Chinese Journal of Contemporary Pediatrics 2021;23(8):828-834
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
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Chemokines
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Child
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Cytokines/metabolism*
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GPI-Linked Proteins/metabolism*
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Humans
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Hyperlipidemias
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Lectins/metabolism*
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Lipids
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Nephrotic Syndrome/drug therapy*
;
Proteinuria
3.Relations of nuclear factor-kappa B activity in the kidney of children with primary nephrotic syndrome to clinical manifestations, pathological types, and urinary protein excretion.
Hong-yang ZHAO ; Ruo-peng SUN ; Jun-hua DONG ; Jun-hui ZHEN
Chinese Medical Journal 2005;118(10):854-856
Child
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Child, Preschool
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Female
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Humans
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Kidney
;
metabolism
;
Male
;
NF-kappa B
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antagonists & inhibitors
;
metabolism
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Nephrotic Syndrome
;
drug therapy
;
metabolism
;
Proteinuria
;
metabolism
4.Does Albumin Preinfusion Potentiate Diuretic Action of Furosemide in Patients with Nephrotic Syndrome?.
Ki Young NA ; Jin Suk HAN ; Yon Su KIM ; Curie AHN ; Suhnggwon KIM ; Jung Sang LEE ; Kyun Sup BAE ; In Jin JANG ; Sang Goo SHIN ; Wooseong HUH ; Un Sil JEON
Journal of Korean Medical Science 2001;16(4):448-454
The aim of this cross-over study was to investigate whether albumin infusion before furosemide administration could potentiate the diuretic action of furosemide. Seven patients with nephrotic syndrome were given the following infusions in random order on two separate days: 1) a sham solution followed by 160 mg of furosemide, 2) 100 ml of 20% human albumin followed by 160 mg of furosemide. Urine and serum furosemide concentrations were measured by high-performance liquid chromatography. The increment of urine volume was greater in albumin preinfusion than in furosemide alone. However, the increments of sodium and chloride excretions between furosemide alone and albumin preinfusion were not different. No significant differences in the pharmacokinetic parameters between the two treatments were observed: area under the concentration-time curve (AUC: 12.7+/-2.2 vs 15.1+/-4.4 g/ml hr), total plasma clearance (253+/-41 vs 256+/-54 ml/min), volume of distribution (341+/-34 vs 494+/-153 ml/kg), elimination half life (4.0+/-1.1 vs 4.6+/-0.8 hr), and urine furosemide excretion of the administered amount (16.5+/-7.3 vs 7.5+/-1.6%). In conclusion, these data show that albumin preinfusion potentiated diuresis, but not natriuresis, of furosemide without any change in the pharmacokinetics of the agent in patients with nephrotic syndrome.
Adolescence
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Adult
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Aged
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Albumins/*pharmacology
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Cross-Over Studies
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Diuretics/*pharmacology
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Drug Synergism
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Female
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Furosemide/*pharmacology
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Human
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Male
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Middle Age
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Nephrotic Syndrome/*drug therapy/metabolism
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Serum Albumin/analysis
5.Pax2 expression in children with steroid-resistant primary nephrotic syndrome.
Hui-Qiong ZHANG ; Zhu-Wen YI ; Xiao-Jie HE ; Xi-Qiang DANG ; Qing-Nan HE ; Shuang-Hong MO
Journal of Central South University(Medical Sciences) 2005;30(5):597-600
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
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Child
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Child, Preschool
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Drug Resistance
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Female
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Glucocorticoids
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therapeutic use
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Humans
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Male
;
Nephrotic Syndrome
;
drug therapy
;
metabolism
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PAX2 Transcription Factor
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biosynthesis
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genetics
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Tumor Suppressor Protein p53
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biosynthesis
;
genetics
6.Change of transforming growth factor beta in peripheral blood mononuclear cell of children with nephrotic syndrome and its significance.
Li YU ; Zhi-yuan WENG ; Zhi-min ZHONG ; Chun-hua ZENG ; You-xiang ZHANG ; Mei-ying ZHUO
Chinese Journal of Pediatrics 2003;41(7):534-537
OBJECTIVEIdiopathic nephrotic syndrome (INS) is a common glomerular disease. The pathogenesis of the disease remains unclear. Recent studies indicate that transforming growth factor beta (TGF beta) is the main cytokine involved in glomerular disease. It plays an important role in the development of INS and in occurrence of glomerulosclerosis. The present study aimed to study changes and significance of TGF beta in children with idiopathic nephrotic syndrome (INS).
METHODSTotally 35 cases with INS (13 males, 22 females) were studied. The age of onset was between 2 years and 1 months and 14 years with an average of 8 years and 3 months. The active stage group had 35 cases and the remission stage groups had 25 cases. The cases in active stage group had first onset of the disease with obvious clinical symptoms and abnormal laboratory findings without use of corticosteroids. The cases in remission stage group were asymptomatic without abnormal laboratory findings. Protein in urine was negative over 4 weeks after oral administration of prednisone for 8 weeks. Twenty five cases were steroid responsive and 10 cases were steroid non-responsive among the 35 cases. Thirty healthy young children were enrolled as control. TGF beta was detected by ELISA in peripheral blood mononuclear cell (PBMC) culture medium. The TGF beta mRNA gene expression was measured by in situ PCR in PBMC.
RESULTS(1) Concentration of TGF beta(247 +/- 26) ng/L and TGF beta mRNA expression (0.57 +/- 0.18) in active stage of simple type or nephritis type INS were higher than those of remission stage and control (P < 0.01). Concentration of TGF beta[(125 +/- 16) ng/L] and TGF beta mRNA expression (0.30 +/- 0.12) in remission stage were higher than that of control (P < 0.05). (2) The level of TGF beta protein in nephritis type [(275 +/- 26) ng/L] was significantly higher than that in simple type [(220 +/- 18) ng/L] in active stage INS (t = 6.45, P < 0.01). No significant difference in TGF beta mRNA expression was found between the nephritis type (0.58 +/- 0.15) and simple type (0.55 +/- 0.16) in active stage INS, either (P > 0.05). But these two types were different from the control (P < 0.01). (3) Concentration of TGF beta and TGF beta mRNA expression after therapy was clearly lower than that before therapy in steroid responsive group (P < 0.01). Whereas no significant change was seen in steroid non-responsive group. Both indicators were higher in steroid non-responsive group than in steroid responsive group whether before or after therapy.
CONCLUSIONTGF beta may play an important role in the mechanism of INS and its level in PBMC can be used as an immunological indicator for the illness state, therefore, determination of TGF beta level and mRNA may be of some clinical significance.
Adolescent ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Nephrotic Syndrome ; blood ; drug therapy ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta ; genetics ; metabolism
7.Interleukin-18 expression in peripheral blood mononuclear cells in children with steroid-resistant nephrotic syndrome.
Hong-Kun JIANG ; Gang LUO ; Hong JIANG
Chinese Journal of Contemporary Pediatrics 2009;11(5):337-340
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
8.Effect of triptergium wilfordii polyglycosidium on content of Th1 and Th2 in child recurrent nephrotic syndrome.
Guo-Hua HU ; Zhu-Wen YI ; Jing-He WANG ; Jing-Chan YAO
China Journal of Chinese Materia Medica 2008;33(4):441-443
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
9.Progress in mitochondrial nephropathy.
Chinese Journal of Pediatrics 2014;52(7):503-505
Alkyl and Aryl Transferases
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genetics
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Child
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DNA, Mitochondrial
;
genetics
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Fibroblasts
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metabolism
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Glomerulosclerosis, Focal Segmental
;
diagnosis
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drug therapy
;
genetics
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Humans
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Kidney Diseases
;
diagnosis
;
drug therapy
;
genetics
;
Mitochondrial Diseases
;
diagnosis
;
drug therapy
;
genetics
;
Mutation
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Nephrotic Syndrome
;
diagnosis
;
drug therapy
;
genetics
;
Protein Kinases
;
genetics
;
Ubiquinone
;
analogs & derivatives
;
biosynthesis
;
deficiency
;
therapeutic use
10.Treatment of children with steroid-dependent nephrotic syndrome with rituximab.
Jianping HUANG ; Juan DU ; Shuo WANG ; Lili XIAO ; Xiaoyan ZHAO
Chinese Journal of Pediatrics 2014;52(7):521-524
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