Fu–Keung Li

Mycophenolate mofetil (MMF) and the sequential use of cyclophosphamide followed by azathioprine (CTX-AZA) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis (DPLN), but MMF is associated with less drug toxicity. Results from an extended long-term study, with median follow-up of 63 mo, that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented. Thirty-three patients were randomized to receive MMF, and 31 were randomized to the CTX-AZA treatment arm, both in combination with prednisolone. More than 90% in each group responded favorably (complete or partial remission) to induction treatment. Serum creatinine in both groups remained stable and comparable over time. Creatinine clearance increased significantly in the MMF group, but the between-group difference was insignificant. Improvements in serology and proteinuria were comparable between the two groups. A total of 6.3% in the MMF group and 10.0% of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up (P = 0.667). Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients (11 and nine patients relapsed, respectively) and between those with MMF treatment for 12 or >/=24 mo. MMF treatment was associated with fewer infections and infections that required hospitalization (P = 0.013 and 0.014, respectively). Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death (P = 0.062 by survival analysis). It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients.

A retrospective single-center cohort study was conducted on 35 patients with diffuse proliferative (WHO type IV) and/or membranous (type V) lupus nephritis (22 with type IV, 6 with type V, and 7 with type IV plus V) who had been treated with a sequential regimen comprising prednisolone and cyclophosphamide during active disease, followed by low-dose prednisolone and azathioprine maintenance. The follow-up period was 33.2 +/- 4.5 months. At presentation, 32 (91.4%) patients were nephrotic, and an abnormal serum creatinine level was noted in 14 (48.3%) patients with type IV changes. Cyclophosphamide was given for 26.8 +/- 2.8 weeks. 33 (94.3%) patients achieved complete or partial renal remissions: 77.3 and 22.7% of the type IV patients, 16.7 and 66.6% of the type V patients, and 14.3 and 71.4% of the type IV plus V patients, respectively (p < 0.0001 for type IV versus type V and for type IV versus type IV plus V). The duration of therapy before renal remissions and normalization of C3 were attained was similar among the three groups of patients. Disease relapse occurred in 4 (18.2%) of 22 IV patients and in 1 of the 5 type V patients in remission. Mortality was not observed, and none of the patients had an increase in serum creatinine level to double the baseline value. Adverse effects related to therapy included: hair loss (42.9%), transient amenorrhea (53.6%), leukopenia (11.4%), febrile episodes (14.3%), and herpes zoster(28.6%). We conclude that sequential use of prednisolone and cyclophosphamide followed by low-dose prednisolone and azathioprine can achieve favorable therapeutic results in the majority of patients with diffuse proliferative and/or membranous lupus nephritis, without excessive toxicities.

OBJECTIVE: To determine the risk factors and outcomes of peritonitis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Episodes of E. coli CAPD peritonitis in our unit from October 1994 to August 2003 were reviewed. Demographic data, underlying medical conditions, recent use of gastric acid inhibitors (including H2 antagonist and proton pump inhibitor), recent antibiotic therapy, antibiotic regimen for peritonitis episodes, sensitivity test results of the E. coli isolated, and clinical outcomes were examined. RESULTS: Over a 10-year study period, 88 episodes of E. coli peritonitis were recorded; 11 of the 88 cases were caused by ESBL-producing E. coli. Recent use of cephalosporins and gastric acid inhibitor were associated with the development of ESBL-producing E. coil peritonitis. Compared with non-ESBL-producing E. coli peritonitis, more cases in the ESBL-producing E. coli group developed treatment failure (45.5% vs 13.0%, p = 0.02) and died of sepsis (27.3% vs 3.9%, p = 0.02). Peritoneal failure rate was higher in the ESBL-producing E. coli group, although the difference was not statistically significant (18.2% vs 3.9%, p = 0.12). CONCLUSION: Peritonitis caused by ESBL-producing E. coli is associated with worse clinical outcomes. The use of cephalosporins and gastric acid inhibitors may contribute to its development. Further studies are warranted to investigate and determine the predisposing factors for ESBL-producing E. coli peritonitis.