PROGRESSION AND REMISSION OF RENAL-DISEASE IN THE LUPUS NEPHRITIS COLLABORATIVE STUDY - RESULTS OF TREATMENT WITH PREDNISONE AND SHORT-TERM ORAL CYCLOPHOSPHAMIDE

Objective: To describe the clinical course of severe lupus nephritis and to identify the risk factors for progression to renal failure among patients treated with prednisone and short-term courses of low-dose oral cyclophosphamide. Design: Ancillary analyses of data from the Lupus Nephritis Collaborative Study (LNCS). Setting: University hospital medical centers (14). Patients: The 86 patients who participated in the LNCS (mean follow-up, 136 weeks [2.6 years]) and a subgroup of 63 patients with follow-up of more than 48 weeks (mean follow-up, 160 weeks [3.1 years]). Measurements: Initial clinical and pathologic features, response to therapy within 48 weeks, and subsequent clinical events, including development of renal failure. Main Results: Renal failure developed in 18 patients (21%). An observed elevation in serum creatinine concentration was the only initial feature predictive of subsequent renal failure. Mean (+/- SD) initial serum creatinine levels were higher in patients who subsequently developed renal failure (244 +/- 134-mu-mol/L [2.76 +/- 1.52 mg/dL] compared with 163 +/- 103-mu-mol/L [1.85 +/- 1.17 mg/dL]; P = 0.007). The risk for renal failure was higher among patients with initial serum creatinine levels greater than 106-mu-mol/L (1.2 mg/dL) (29% compared with 6.5%; P = 0.014). Response to therapy (defined as resolution of initial serum creatinine elevations within 48 weeks) refined the prognosis based on initial serum creatinine determinations. The risk for subsequent renal failure was higher among patients who failed to respond to therapy within 48 weeks (30% compared with 0%; P = 0.015). By comparison, 9% of patients with normal initial serum creatinine levels progressed to renal failure after 48 weeks. Conclusions: Initial serum creatinine levels and responses to initial therapy with prednisone and short-term cyclophosphamide, as used in the LNCS, can guide further therapy. Patients with normal initial serum creatinine levels or resolution of initial serum creatinine elevations within 48 weeks have a low risk for renal failure and may not require long-term treatment with cyclophosphamide.