Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring

Abstract

Objective 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). Methods 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. Results 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). Conclusion 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.

Correlation between serum complement component 4 levels and tubular atrophy in patients with lupus nephritis

“…Specifically, each 0.01 g/L increase in serum C4 was linked to a 6.9% higher risk of developing tubular atrophy. This result contrasts with previous studies, which reported no significant correlation between serum complement levels and interstitial fibrosis or tubular atrophy (IF/TA) [ 1 , 2 , 12 , 13 ]. The discrepancies between our findings and those of earlier studies may be attributed to variations in the classification of interstitial fibrosis and tubular atrophy or differences in sample sizes across the studies.…”

Renal prognosis a long time after renal biopsy on patients with diabetic nephropathy

“…In our retrospective study, IFTA and interstitial inflammation had a strong impact on the renal prognosis, as well as in Okada's study [10], and this result was also in agreement with the findings reported for other renal diseases such as IgA nephropathy and lupus nephritis [17, 18]. However, with respect to glomerular lesions, there was a significant difference in the renal survival rate between glomerular class IIA and classes IIB or III in our study, unlike the findings of Okada [10].…”

Inflammation in areas of fibrosis precedes loss of kidney function in lupus nephritis

“…IFTA is a well-established marker of injury severity and is a strong predictor of CKD progression in various kidney diseases, including in LN. 10 13 Consistent with the previous findings, 10 our study confirmed that higher IFTA correlates with higher risk of GFR loss. The risk within IFTA was significantly influenced by the degree of the inflammatory infiltrate (i-IFTA).…”