Literature DB >> 16544177

Deoxyspergualin, an immunosuppressant, in patients suffering from nephropathies with crescent formation: an open-label trial to evaluate safety and efficacy.

Hirokazu Imai1, Osamu Hotta, Mitsuhiro Yoshimura, Tsuneo Konta, Yoshiharu Tsubakihara, Masanobu Miyazaki, Chie Tomida, Masaki Kobayashi, Satoshi Suzuki, Hideo Shiiki, Atsushi Yamauchi, Hitoshi Yokoyama, Masato Nose.   

Abstract

BACKGROUND: Crescent formation in glomeruli means an acute active lesion that develops a rapidly progressive course. Therapies using pulse methylprednisolone, oral corticosteroids, and cyclophosphamide are recommended, but no agreement has been reached on the optimal therapy. There have been no controlled trials, because of the severity of this condition and because withholding treatment would become an ethical issue.
METHODS: We evaluated the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant, in a multicenter, prospective trial of 44 patients with crescent formation in over 10% of glomeruli, who were randomly placed into groups that received daily doses of 0.1 mg/kg (n = 21) and 0.2 mg/kg (n = 23) of DSG, given by a 1-h infusion for 4 weeks, and who were then monitored for 3 months. All patients received DSG in this open-label prospective study. We evaluated the levels of urinary protein and hematuria, and examined renal function after the DSG treatment.
RESULTS: Urinary protein significantly decreased with each dose after starting the DSG administration and this efficacy was sustained for 2 months after the discontinuation of DSG. In the groups receiving 0.1 mg/kg and 0.2 mg/kg, mean urinary protein levels were 2.1 g/day and 2.3 g/day at the initiation of the DSG administration, 1.4 g/day and 1.6 g/day at week 4, and 1.5 g/day and 1.3 g/day at week 12, respectively. Hematuria was markedly improved by a dose of 0.2 mg/kg and was not exacerbated following the termination of DSG. Exacerbation of renal dysfunction, as measured by creatinine clearance, serum creatinine, and blood urea nitrogen was prevented by both doses of DSG. The most common adverse reaction was reversible neutropenia.
CONCLUSIONS: Short-term treatment with DSG may be effective and tolerated in patients suffering from nephropathies with crescent formation.

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Year:  2006        PMID: 16544177     DOI: 10.1007/s10157-005-0396-1

Source DB:  PubMed          Journal:  Clin Exp Nephrol        ISSN: 1342-1751            Impact factor:   2.801


  37 in total

1.  A novel rescue drug, 15-deoxyspergualin. First clinical trials for recurrent graft rejection in renal recipients.

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Journal:  Transplantation       Date:  1990-02       Impact factor: 4.939

2.  15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis.

Authors:  Rainer Birck; Mark Newman; Claude Braun; Irmgard Neumann; Kyuichi Nemoto; Benito Yard; Rüdiger Waldherr; Fokko J van der Woude
Journal:  Nephrol Dial Transplant       Date:  2005-09-02       Impact factor: 5.992

3.  Mechanism of action of 15-deoxyspergualin. I. Suppressive effect on the induction of alloreactive secondary cytotoxic T lymphocytes in vivo and in vitro.

Authors:  K Nishimura; T Tokunaga
Journal:  Immunology       Date:  1989-09       Impact factor: 7.397

4.  Unique action of an immunosuppressive agent, deoxyspergualin, on hematopoiesis in mice.

Authors:  K Nemoto; M Ogino; A Ohinata; K Hirashima
Journal:  Exp Hematol       Date:  1997-12       Impact factor: 3.084

5.  Prolonged treatment of refractory Wegener's granulomatosis with 15-deoxyspergualin: an open study in seven patients.

Authors:  Wilhelm H Schmitt; Rainer Birck; Peter A Heinzel; Ursula Göbel; Mira Choi; Klaus Warnatz; Hans H Peter; Fokko J van der Woude
Journal:  Nephrol Dial Transplant       Date:  2005-04-12       Impact factor: 5.992

6.  Treatment of vasculitic IgA nephropathy.

Authors:  L Harper; M A Ferreira; A J Howie; C O Savage; N T Richards; J Michael; D Adu
Journal:  J Nephrol       Date:  2000 Sep-Oct       Impact factor: 3.902

7.  15-Deoxyspergualin "rescue therapy" for methylprednisolone-resistant rejection of renal transplants as compared with anti-T cell monoclonal antibody (OKT3).

Authors:  M Okubo; K Tamura; K Kamata; Y Tsukamoto; Y Nakayama; T Osakabe; K Sato; M Go; K Kumano; T Endo
Journal:  Transplantation       Date:  1993-03       Impact factor: 4.939

8.  Deoxyspergualin preferentially inhibits the growth and maturation of anti-CD40-activated surface IgD+ B lymphocytes.

Authors:  K Morikawa; K Nemoto; T Miyawaki; S Morikawa
Journal:  Clin Exp Immunol       Date:  1998-06       Impact factor: 4.330

9.  In vitro immunosuppressive properties of spergualins to murine T cell response.

Authors:  H Fujii; T Takada; K Nemoto; F Abe; A Fujii; T Takeuchi
Journal:  J Antibiot (Tokyo)       Date:  1989-05       Impact factor: 2.649

10.  Rejection associated with early appearance of donor-reactive antibodies after kidney transplantation treated with plasmapheresis and administration of 15-deoxyspergualin. A report of two cases.

Authors:  G Gannedahl; S Ohlman; U Persson; S Gudmundsson; E Larsson; G Tydén; T H Tötterman; B Wikström; L Weiss; C G Groth
Journal:  Transpl Int       Date:  1992-09       Impact factor: 3.782

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  4 in total

1.  Is there B cell involvement in a rat model of spontaneous idiopathic nephrotic syndrome treated with LF15-0195?

Authors:  Ludmilla Le Berre; Gaëlle Tilly; Jacques Dantal
Journal:  J Nephrol       Date:  2014-03-25       Impact factor: 3.902

2.  Interventions for renal vasculitis in adults.

Authors:  Giles D Walters; Narelle S Willis; Tess E Cooper; Jonathan C Craig
Journal:  Cochrane Database Syst Rev       Date:  2020-01-13

Review 3.  HSPA8/HSC70 in Immune Disorders: A Molecular Rheostat that Adjusts Chaperone-Mediated Autophagy Substrates.

Authors:  Srinivasa Reddy Bonam; Marc Ruff; Sylviane Muller
Journal:  Cells       Date:  2019-08-07       Impact factor: 6.600

4.  Efficacy of deoxyspergualine for antibody-mediated rejection and proteinuria after kidney transplantation.

Authors:  Hideki Ishida; Kazunari Tanabe
Journal:  Ther Clin Risk Manag       Date:  2008-06       Impact factor: 2.423

  4 in total

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