Long-term effects of immunosuppressants in steroid-dependent nephrotic syndrome

Takeda, Atsushi; Ohgushi, Hiroaki; Niimura, Fumio; Matsutani, Hidetomo

doi:10.1007/s004670050538

Cited by 20 publications

(19 citation statements)

References 17 publications

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“…It resulted in cumulative relapse free survival of 78.3% at the last follow up. Some earlier reports also suggested a superior effect of CHL over other alkylating agents [18,25,26]. But the straightforward comparison of the domestic and international treatment regimes is relative since in our patients the dosage of CHL was generally higher than standard one.…”

Section: Discussioncontrasting

confidence: 46%

“…under the SSNS are not presented in the Western literature. The data concerning the use of CHL are nowadays rarely presented being usually reported in the earlier studies [18,25,26].…”

Section: Discussionmentioning

confidence: 98%

“…Nevertheless, CYC I.V. is usually recommended as an optional treatment to maintain remission in SSNS [7,11,[13][14][15][16][17][18][19][20][21][22]. In different studies, the percentage of relapse-free patients varies between 5 and 67% during 24 months, and between 17 and 65% during 60 months, respectively [5,18,[19][20][21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

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Clinical Course of Steroid Sensitive Nephrotic Syndrome in Children: Outcome and Outlook

Fomina¹

2011

TOPEDJ

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Abstract:Introduction: The aim of our study was to investigate the relative efficiency and adverse effects of various treatments of steroid sensitive nephrotic syndrome (SSNS) in children, and to determine factors associated with relapse risk in these patients. Materials and Method:We retrospectively studied the data from 690 SSNS children treated in referral center over 25 years. The analyzed treatment protocols were: Prednisolone (PRED, eight weeks in a dose 1.5-2.0 mg/kg, then it tapering and given for 9-12 months), Chlorambucil (CHL, cumulative dose 28.5-30 mg/kg), Cyclophosphamide intravenously (CYC I.V., cumulative dose of 30-36 mg/kg, then supporting dose of CHL, cumulative dose of 20-25 mg/kg) and intramuscular (CYC I.M., cumulative dose of 120-150 mg/kg). The alkylating agents were used after remission induction by PRED and under its protection.Results: Cumulative relapse-free survival was 81.9%, 69.0% and 64.5% after 12, 36 and 60 months, respectively. In multivariate analyses, relapse risk was associated with age of treatment (<6 years), and both PRED and CYC I.V. The only predictive factor for early relapse was PRED, unlike two and more relapses group where PRED and CYC I.V. as well as age from 3 to 6 years was highly prognostic. The high probability of sustained remission in combination with relatively mild adverse effects was observed for PRED used at first episode and CHL used at relapse. Conclusion:To summarize, our protocols characterized by the prolonged PRED and CHL demonstrated promising results and should be considered as an efficient alternative strategy in SSNS management.

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Section: Discussioncontrasting

confidence: 46%

“…under the SSNS are not presented in the Western literature. The data concerning the use of CHL are nowadays rarely presented being usually reported in the earlier studies [18,25,26].…”

Section: Discussionmentioning

confidence: 98%

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Clinical Course of Steroid Sensitive Nephrotic Syndrome in Children: Outcome and Outlook

Fomina¹

2011

TOPEDJ

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“…In addition, the variable responses to steroids among MCNS patients do not have an apparent attribution to the characteristics of the patients’ glucocorticoid receptors [5]. Furthermore, children with steroid-dependent nephrotic syndrome also responded variably to immunosuppressive and immunostimulating drugs [6,7]. These findings suggest that steroid dependence does not solely rely on the immune mechanisms.…”

Section: Introductionmentioning

confidence: 83%

Angiotensin-Converting Enzyme Gene Polymorphism in Children with Idiopathic Nephrotic Syndrome

Tsai

Yang²,

Lin³

et al. 2006

Am J Nephrol

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Aims: To investigate the genetic polymorphism of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) in children with idiopathic nephrotic syndrome (INS), as well as its relationship with patient’s clinical response to steroid therapy. Methods: Fifty-nine patients with INS were recruited and divided into 2 groups according to their clinical response to steroids: steroid-sensitive (SS) with 19 patients and non-SS with 40 patients, which was further divided into steroid-dependent (SD) and steroid-resistant (SR) groups with 35 and 5 patients, respectively. Seventy-nine children without previous renal diseases and negative proteinuria were enrolled as a control group. The genotypes for ACE I/D polymorphism, including DD, ID, and II, were analyzed. Results: The distribution of ACE DD, ID, and II genotypes in INS patients were 52.5, 10.2 and 37.3%, respectively; the corresponding numbers for the control group were 2.5, 25.3 and 72.2%, respectively. Patients with INS had a significantly higher percentage of DD genotype (p <0.001) than the control group. This higher incidence of the DD genotype was observed in both the SS and non-SS groups. A higher percentage of the DD genotype in the non-SS group and in the SD group as compared to the SS group (both p < 0.05) was also noted. Conclusion: Our data shows that INS is associated with a higher incidence of the DD genotype, especially in non-SS patients. This finding suggests that the DD genotype may be a risk factor for INS and play a role in the clinical response to steroids.

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“…To date, a large number of studies have indicated that podocyte injury, loss and dysfunction have an important role in pathologies including focal segmental glomerulosclerosis and membranous nephropathy (3)(4)(5). Immunosuppressants (e.g., steroids or cyclosporine A) have been used based on anecdotal evidence to treat NS (6). Unless a contraindication exists, glucocorticoids (GC) continue to be the first-line therapy (7).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury

et al. 2018

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Abstract. Nephrotic syndrome (NS) is the most common kidney disease in clinical practice and may lead to end-stage renal failure. Astragalosides (AST) have been clinically tested for the treatment of NS, but their mechanism of action has remained to be elucidated. The aim of the present study was to investigate the effect of AST on the structure and function of podocytes with adriamycin (ADR)-induced damage and to elucidate the underlying molecular mechanisms. The mouse podocyte clone 5 (MPC5) immortalized mouse podocyte cell line was treated with 0.5 µmol/l ADR to establish a podocyte injury model. The MPC5 podocytes were divided into a control group, a podocyte injury group and a low-, medium-and high-concentration AST treatment group. The results indicated that the survival rate of the podocyte injury group was significantly decreased compared with that in the control group and each AST-treated group had an increased survival rate compared with that in the podocyte injury group. Furthermore, each dose of AST significantly inhibited the ADR-associated increases the levels of lactate dehydrogenase and malondialdehyde and the decrease in the activity of superoxide dismutase in MPC5 podocytes. In addition, AST improved the migration ability of MPC5 podocytes and suppressed the cytoskeletal rearrangement associated with ADR-induced damage. Furthermore, matrix metalloproteinase (MMP)-2 and -9 were decreased in the podocyte injury group, which was inhibited by different concentrations of AST. Thus, AST was able to maintain the balance of oxidative stress in podocytes cultured with ADR and protect them from ADR-induced injury. The mechanism may be associated with the upregulation of MMPs.

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Long-term effects of immunosuppressants in steroid-dependent nephrotic syndrome

Cited by 20 publications

References 17 publications

Clinical Course of Steroid Sensitive Nephrotic Syndrome in Children: Outcome and Outlook

Clinical Course of Steroid Sensitive Nephrotic Syndrome in Children: Outcome and Outlook

Angiotensin-Converting Enzyme Gene Polymorphism in Children with Idiopathic Nephrotic Syndrome

Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury

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