Tubulointerstitial damage predicts end stage renal disease in lupus nephritis with preserved to moderately impaired renal function: A retrospective cohort study

Abstract

Objectives The presence of tubulointerstitial damage (TID) on renal biopsy is considered to be a late sequela of lupus nephritis (LN). The objective of this study was to determine if TID predicts progression to end stage renal disease (ESRD) in LN patients without advanced kidney disease. Methods All SLE patients with an index biopsy consistent with LN between January 2005 and July 2015, and eGFR≥30 mL/min/1.73m2 were included. Moderate-to-severe TID was defined as the presence of moderate to severe tubular atrophy and/or interstitial fibrosis. Time to ESRD was defined as time from the index biopsy date to incident ESRD date; non-ESRD patients were censored at time of death or the last visit before December 2015. Time-dependent analyses were conducted to evaluate whether moderate to severe TID was predictive of ESRD progression. Results Of the 131 LN patients with eGFR≥30 mL/min/1.73m2, 17 (13%) patients progressed to ESRD. Moderate-to-severe TID was present in 13% of biopsies with eGFR≥60 mL/min/1.73m2 and in 33% of biopsies with eGFR between 30 and 60 mL/min/1.73m2. Moderate-to-severe TID was associated with a higher risk of ESRD progression: adjusted hazard ratio (HR) = 4.1, 95% CI (1.4, 12.1), p=0.01 for eGFR≥30 mL/min/1.73m2; HR 6.2, 95% CI (1.7, 23.2), p=0.008 for eGFR≥60 mL/min/1.73m2. There was no association between tubulointerstitial inflammation (TII) and ESRD progression. Conclusions Moderate-to-severe TID, but not TII, was a strong predictor of ESRD progression independent of eGFR or glomerular findings, therefore, providing an important window for potential early interventions.

Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring

“…In the current study, both moderate-to-severe TII and IF/TA were associated with proliferative LN and eGFR, as previously described (2,6). African American race was associated with moderate-to-severe TII.…”

“…A growing body of evidence indicates that indices of tubulointerstitial damage (TID) are better predictors of progression to renal failure than glomerular parameters (2)(3)(4). Both tubulointerstitial inflammation (TII) and tubulointerstitial scarring, namely interstitial fibrosis and tubular atrophy (IF/TA), strongly correlate with poor renal outcomes independent of the extent of glomerular damage (2,3,5,6).…”

Management of lupus nephritis: a systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations

“…Specifically, tubulointerstitial lesions, especially interstitial fibrosis, tubular atrophy or their combination, have been associated with increased risk of ESKD or a composite outcome, in retrospective observational studies. 38 40–42 In a retrospective study of 105 patients with initial renal biopsy between 1987 and 2011 and a 10-year follow-up, presence of interstitial fibrosis/tubular atrophy in >25% of biopsy area was associated with an almost fourfold increased risk for ESKD (HR: 3.89, 95% CI 1.25 to 12.14). 43 Additionally, evidence of thrombotic microangiopathy may be present in 5–25% of patients with LN.…”

Intrarenal activation of adaptive immune effectors is associated with tubular damage and impaired renal function in lupus nephritis

“…Tubulointerstitial lesions were previously already identified as a prognostic marker in LN. [33][34][35][36][37] Interstitial infiltration by inflammatory cells and tubular atrophy potentially result from or are amplified by several kinds of insults in the context of LN: proteinuria, deposition of immune complexes in the interstitium, rupture of the Bowman's capsule and presentation of cryptic antigens by juxtaglomerular antigen-presenting cells, induction of proinflammatory molecules at the surface of renal tubular cells from the adaptive immune system in the interstitium of lupus kidney biopsies, organised either in T and B cell aggregates, or in germinal centres in the presence of CD21+ follicular dendritic cells. By sequencing the Ig repertoire of one germinal centre and four T:B cell aggregates, they found evidence of clonal restriction in all samples tested, and extensive somatic hypermutation in all but one T and B cell aggregate, in line with an antigen-driven clonal selection.…”