THE BENEFIT OF EARLY TREATMENT WITH IMMUNOSUPPRESSIVE AGENTS IN LUPUSNEPHRITIS

Objective. In a cohort of 87 patients with lupus nephritis, delay betw een the detection of the onset of renal disease and renal biopsy was a significant predictor at the time of a first renal biopsy for subsequ ent renal insufficiency (relative risk = 4.4; 95% confidence interval = 1.7 to 14.5; p < 0.001) and death due to lupus renal involvement (re lative risk = 6.7; 95% confidence interval = 2.1 to 21.2; p < 0.001). We evaluated the role of lead time bias, 2 variants of prognostic sele ction bias (length biased sampling), and the benefit of early treatmen t as explanations for this effect. Methods and Results. Evaluation usi ng the time of renal onset rather than the time of renal biopsy for th e analysis suggested that lead time bias was unlikely to be an explana tion for the effect of duration on renal insufficiency or death due to renal involvement. Identical values of age, serum creatinine and 24 h our urinary protein excretion at renal onset for those with a long dur ation versus short duration prior to biopsy, suggested that difference s in prognostic selection were unlikely to explain the observed result s. A 2nd type of prognostic selection bias arising from the failure to include patients who did not undergo a renal biopsy was further asses sed by statistical simulation. The results of this approach indicated that prognostic selection bias was not solely responsible for the sign ificant associations. Because treatment with high dose prednisone and immunosuppressive drugs was not instituted until a renal biopsy had be en performed, delay in instituting these therapies remained a possible explanation for the increased frequency of renal insufficiency and de ath due to renal involvement observed in those with longer delays befo re renal biopsy. In addition, there was significant deterioration in s erum creatinine (median change 0.6 mg/dl) and 24 hour urinary protein excretion (median change 2.5 gm) over the period from renal onset to r enal biopsy, and significantly higher scores for the activity, chronic ity and tubulointerstitial indices on renal biopsy in those in whom th erapy was delayed. Conclusion. Prompt therapy with prednisone and immu nosuppressive agents in lupus nephritis has a beneficial effect on lon gterm prognosis.