Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Abstract

Objective. To determine the cumulative rate of relapse of lupus nephritis that has been treated successfully with cyclophosphamide (CYC), and to estimate the association between time to relapse and demographic, clinical, laboratory, and treatment variables.Methods. This was an observational study of 48 systemic lupus erythematosus (SLE) patients who were treated successfully with CYC between 1979 and 1993 and followed up thereafter a t 3 university hospitals. Demographic and clinical variables, laboratory data during the first month of nephritis, and therapy-related variables were recorded from charts. Renal biopsy specimens were retrieved and analyzed by a pathologist. Relapse of nephritis was the outcome of interest. Descriptive analysis of patients who did and those who did not have a relapse was performed by chi-square test, Fisher's exact test, and Wilcoxon 2-sample test. The cumulative rate of relapse was computed using the actuarial method. Univariate comparisons of time to relapse were computed by log-rank test. Proportional hazards modeling was used to assess the combined effect of patient characteristics that have been hypothesized to be prognostic factors.ResuZts. Nephritis relapsed in 11 patients. Previous hematologic disorder, arthritis or arthralgia, and the use of CYC in oral form were more frequent in patients who had a relapse. The cumulative rate of relapse was 25% and 46% at 5 years and 10 years, respectively. A significant univariate difference in time to relapse was found when patients were stratified by Renal disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) (1-4). The use of immunosuppressive agents has been associated with a better prognosis (5-12). Combined cyclophosphamide (CYC) and glucocorticoid therapy is deemed to yield significant improvement in renal survival (13-15) and positive economic impact, compared with glucocorticoid therapy alone (16). However, several questions regarding the use of CYC in lupus nephritis remain unresolved. The optimum dosage, length of therapy, and method of administration have not been fully established. Toxicity and side effects are major limiting factors.The rate of relapse of nephritis following CYC therapy is largely unknown. This issue is important because recurrent episodes of nephritis may lead to progressive renal failure. In various studies, the rate of relapse of nephritis has ranged between 0 and 50%. However, followup of patients in these studies was short or was not mentioned in the reports (11,13,(17)(18)(19). Boumpas et a1 (20) and found that short courses of intravenous CYC pulses were associated with a higher rate of disease exacerbation than were longer courses. Information regarding the influence of demographic and clinical variables, renal histology, and methods of CYC administration is lack-

Value of a Complete or Partial Remission in Severe Lupus Nephritis

“…The definitions for remission, often referred to as complete, range from those that require a reduction in proteinuria to essentially normal levels Ͻ0.3 to 0.5 g/d (6,8,(27)(28)(29)(30) to those that require improvement to Յ1.0 g/d (9,31) and those that require only a Ն30% reduction in proteinuria to Ͻ3 g/d (32). In addition, renal function as measured by serum creatinine level must be normal in some studies (6,27), whereas in others, it must be "stable" (i.e., Ͻ30% rise in serum creatinine) or "improved" (9,28) or there must be a lack of doubling serum creatinine (31). In our study, we chose to apply the term CR to patients who achieved a normalization in renal function and proteinuria because the outcome for these patients is significantly improved over that for patients with NR.…”

Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare

“…Many studies have reported the incidence of renal fl ares of lupus nephritis after initial remission with steroid and cyclophosphamide treatment [2,[4][5][6]14]. Ciruelo et al [14] described a cumulative rate of renal relapse of 46 % at 10 years in patients treated with corticosteroid and cyclophosphomide for a median of 31 months.…”

Mycophenolate Mofetil for Remission Induction in Severe Lupus Nephritis

“…Increased time to first renal remission predicts an earlier relapse or renal flare, with rate of renal flare and subsequent response to treatment predicting a worse renal outcome in the longer term [16, 17]. In addition, increased delay to treatment of nephritis with CYC has been found to reflect a group of patients with an increased time to renal remission and higher relapse rate [16]. This suggests that better outcomes might be obtained with a drug like MMF that provides similar rates of renal remission with less toxic adverse effects and thus might be instituted earlier after diagnosis of lupus nephritis than CYC.…”