In lupus nephritis, glomerular injury correlates poorly with progression to renal failure. While the tubulointerstitium is also commonly involved, the importance of such involvement is not well defined. Therefore, we developed a simple method to assess the prognostic utility of measuring tubulointerstitial inflammation (TI).
Sixty-eight SLE patients with lupus nephritis were enrolled. Tubulointerstitial lymphocytic infiltrates were quantitated both by anti-CD45 antibody staining and standard histochemical staining. Follow-up data was obtained and survival analysis carried out to determine which histologic features were predictive of subsequent renal failure.
By CD45 staining TI was a common pathological finding, with 72% of biopsies having moderate or severe involvement. The extent of TI correlated with serum creatinine, but not with dsDNA antibodies, serum C3, or glomerular inflammation. TI severity, but not glomerular injury, identified patients at greater risk for renal failure (p=0.02). A high NIH chronicity index also identified patients at risk for renal failure. However, when the glomerular and tubulointerstitial subcomponents of the NIH chronicity index were separated in a bivariate model, only tubulointerstitial chronicity provided prognostic information (HR 2.2, 95% C.I. 1.3, 3.6, p=0.002 vs. HR 1.0, 95% C.I. 0.7, 1.5. p=0.97 for glomerular chronicity).
TI identifies lupus nephritis patients at greatest risk for progression to renal failure. The immunological mechanisms underlying TI may provide novel targets for therapeutic intervention.