Background/Purpose: Tubulointerstitial disease is frequent in lupus nephritis (LN) with immune deposits being present in up to one third of patients.[1,2] Lesions including interstitial infiltration, tubular atrophy and interstitial fibrosis are all independent risk factors for LN renal outcome.[3] The aim of this retrospective study was to analyze tubulointerstitial changes on a series of repeat renal biopsies (RB) and to identify correlations with clinical variables. 

Methods: Histopathological changes of 39 LN patients were analysed using the revised Austin’s semi-quantitative scoring system, using a grading system of 0 to 3 (0, normal; 1, mild <25%, 2, moderate between 26 and 50%; 3, severe >50% of the interstitium affected).[4] With a similar method, chronicity indices were also calculated and included scores for glomerular sclerosis, fibrous crescents, tubular atrophy and interstitial fibrosis. Spearman’s rank-order correlation was run to determine relationship between clinical variables and histological findings.

Results: Compared to the initial biopsy, we found a progression in both tubular atrophy (p=0.001) and interstitial scarring (p<0.001), but not in inflammatory cell infiltration (p=1.000) by the time of RB. The mean total tubulointerstitial score (± SD) has progressed from 2.69 ± 2.03 to 3.78 ± 2.03 (p=0.001). There was a positive correlation between serum creatinine level and the severity of tubular atrophy at time of both reference biopsy (r=0.33, p=0.048) and RB (r=0.56, p<0.001). In addition serum creatinine at time of RB showed a strong correlation with interstitial scarring (r=0.60, p<0.001). We found no association between any of the other clinical variables and the tubulointerstitial pathology. A trend was identified between the severity of interstitial inflammation on reference biopsy and the amount of tubular atrophy and interstitial scaring on RB (r=0.349, p=0.19; r=0.385, p=0.009, respectively). The mean chronicity index (CI, ± SD) increased from 3.58 ± 2.64 to 5.11 + 2.96 by the time of RBs. Patients with proliferative histopathology on initial biopsy had higher CI at both the reference biopsy (4.03 ± 2.48 vs. 2.57 ± 2.79, proliferatives vs. non-proliferatives, mean score ± SD, p=0.047) and RBs (5.77 ± 2.94 vs. 3.64 ± 2.53, proliferatives vs. non-proliferatives, mean score ± SD, p=0.019). Treatment decisions did not seem to be influenced by the progression of CI (treatment escalation in 60.9% vs. 61.1%, increased CI vs. stable/reduced CI, respectively, p=0.982).  

Conclusion: Not only the glomerular pathology, but tubulointerstitial lesions are also important in LN, and they show progression in time illustrated by our study using RBs. Serum creatinine level showed good correlation with the severity of tubulointerstitial lesions. Correlation was also demonstrated between the amount of interstitial inflammation on reference biopsies and the severity of tubular atrophy and interstitial scaring on RBs, suggesting a possible predictive role of damage.

References

1. O’Dell JR et al. Arch Intern Med 1985; 145: 1996-1999.
2. Park MH et al. Nephron 1986; 44: 309-319.
3. Yu F et al. Kidney Int 2010; 77: 820-829.
4. Yamamoto T et al. Lupus 1993; 2: 261-268.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tubulointerstitial-involvement-in-lupus-nephritis/