title: Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial.
abstract: To evaluate the outcome of low doses of cyclophosphamide (Cyclo) therapy in lupus nephritis (LN) patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min) compared with Group II (55.1 ± 30.1 mL/min), P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05). At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03). The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2). Complete remission was observed in 25 (34.2%) patients in Group I vs. 11 (25%) in Group II (P = 0.288), while partial remission was similar in both groups; 43 (58.9%) patients in Group I vs. 26 (59%) patients in Group II. End-stage renal disease was observed in 10 (13.7%) patients in Group I vs. 9 (20.4%) patients in Group II (P = 0.359). Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000). Moreover, different infections occurred in 23 (31.3%) patients vs. six (13.6%), digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with standard dose.
authors.affiliation: Department of Medicine, King Khalid University Hospital, Kingdom of Saudi Arabia. mitwallia@ngha.med.sa
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Mitwalli
authors.forename: Jamal S
authors.initials: JS
authors.lastname: Al Wakeel
authors.forename: Sameer
authors.initials: S
authors.lastname: Hurraib
authors.forename: Abu
authors.initials: A
authors.lastname: Aisha
authors.forename: Abdulkaraem
authors.initials: A
authors.lastname: Al Suwaida
authors.forename: Awatif
authors.initials: A
authors.lastname: Alam
authors.forename: Durdana
authors.initials: D
authors.lastname: Hammad
authors.forename: Fathia
authors.initials: F
authors.lastname: Sulimani
authors.forename: Nawaz A
authors.initials: NA
authors.lastname: Memon
authors.forename: Akram
authors.initials: A
authors.lastname: Askar
authors.forename: Ali
authors.initials: A
authors.lastname: Al Tuwaijri
authors.forename: Abdo
authors.initials: A
authors.lastname: Qudsi
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide