The benefit of early treatment with immunosuppressive agents in lupus nephritis.

OBJECTIVE

In a cohort of 87 patients with lupus nephritis, delay between the detection of the onset of renal disease and renal biopsy was a significant predictor at the time of a first renal biopsy for subsequent renal insufficiency (relative risk - 4.9; 95% confidence interval = 1.7 to 14.5; p < 0.001) and death due to lupus renal involvement (relative 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 selection bias (length biased sampling), and the benefit of early treatment as explanations for this effect.

METHODS AND RESULTS

Evaluation using the time of renal onset rather than the time of renal biopsy for the analysis suggested that lead time bias was unlikely to be an explanation for the effect of duration on renal insufficiency or death due to renal involvement. Identical values of age, serum creatinine and 24 hour urinary protein excretion at renal onset for those with a long duration versus short duration prior to biopsy, suggested that differences in prognostic selection were unlikely to explain the observed results. A 2nd type of prognostic selection bias arising from the failure to include patients who did not undergo a renal biopsy was further assessed by statistical simulation. The results of this approach indicated that prognostic selection bias was not solely responsible for the significant associations. Because treatment with high dose prednisone and immunosuppressive drugs was not instituted until a renal biopsy had been performed, delay in instituting these therapies remained a possible explanation for the increased frequency of renal insufficiency and death due to renal involvement observed in those with longer delays before renal biopsy. In addition, there was significant deterioration in serum 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 renal biopsy, and significantly higher scores for the activity, chronicity and tubulointerstitial indices on renal biopsy in those in whom therapy was delayed.

CONCLUSION

Prompt therapy with prednisone and immunosuppressive agents in lupus nephritis has a beneficial effect on longterm prognosis.