Deoxyspergualin, an immunosuppressant, in patients suffering from nephropathies with crescent formation: an open-label trial to evaluate safety and efficacy.
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.
Imai
Hirokazu
H
Department of Internal Medicine, Division of Nephrology and Rheumatology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. imaihiro@aichi-med-u.ac.jp
Hotta
Osamu
O
Yoshimura
Mitsuhiro
M
Konta
Tsuneo
T
Tsubakihara
Yoshiharu
Y
Miyazaki
Masanobu
M
Tomida
Chie
C
Kobayashi
Masaki
M
Suzuki
Satoshi
S
Shiiki
Hideo
H
Yamauchi
Atsushi
A
Yokoyama
Hitoshi
H
Nose
Masato
M
D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology; D011247:Pregnancy; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy; D016896:Treatment Outcome
D006146:Guanidines; D007166:Immunosuppressive Agents; D003404:Creatinine; C037258:gusperimus