Background/Purpose: Tubulointerstitial damage (TID), defined as tubulointerstitial inflammation (TII) or interstitial fibrosis/tubular atrophy/ (IF/TA) is associated with poor renal outcomes in lupus nephritis (LN)¹. Glomerular damage is thought to initiate downstream changes that culminate in TID². However, some SLE patients with advanced TID have no significant renal impairment to prompt a renal biopsy, complicating their early recognition. Therefore, we studied whether patients with TID and either none or mild renal impairment at the time of biopsy differ from patients with TID and significant renal impairment. The objective was to identify potential factors that may aid in the early recognition of patients with TID before overt renal dysfunction.

Methods: We identified all patients who fulfilled ACR and/or SLICC criteria for SLE and had an index renal biopsy between 2005 and 2017 with moderate/severe TID. Moderate/severe TID was defined as IF/TA and/or TII involving ≥25% of the biopsied tissue. Significant renal impairment was defined as glomerular filtration rate (eGFR) <60 mL/min/1.73m² at the time of biopsy. The following variables were compared: SLE duration, LN class, history of diabetes, hypertension (HTN) and Sjogren’s syndrome, medications (steroids, hydroxychloroquine, immunosuppressives, non-steroidal anti-inflammatory drugs), demographics and laboratory data (complement, dsDNA, antiphospholipid antibodies, anti-Ro/La, anti-Sm/RNP).

Results: A total of 65 patients with moderate/severe TID were included. Among these patients, 19 (29%) had moderate/severe TII alone, 25 (38%) had moderate/severe IF/TA alone, and 21 (32%) had moderate/severe TII accompanied by moderate/severe IF/TA. Among the 40 patients with moderate/severe TII with or without accompanying IF/TA, 16 (40%) had eGFR ≥60 and 24 (60%) had eGFR<60. Compared to patients with eGFR<60, those with eGFR≥60 had a longer disease duration [median (IQR): 55 (30, 68) vs 17 (3, 26) months, p=0.002], and were less likely to have anti-Ro/La antibodies (6% vs 35%, p=0.04]. Among the 46 patients with moderate/severe IF/TA with or without accompanying TII, 14 (30%) had eGFR≥60 and 32 (70%) had eGFR <60. Compared to patients with eGFR<60, those with eGFR≥60 were younger [28 (16, 33) vs 45 (30, 55) years, p=0.002] and had a higher proportion of Black patients (72% vs. 36%, p=0.02). In this group, patients were more likely to be on steroids at the time of biopsy (100% vs 70%, p=0.03) and HTN was seen less frequently (38% vs 74%, p=0.03). There was no association between eGFR≥60 and LN class or routine serologic markers of disease activity among patients with moderate/severe TII or IF/TA.

Conclusion: Moderate/severe TII and/or IF/TA frequently occur in the absence of significant renal impairment and identifiable markers of early disease, hindering its timely recognition. At the time of biopsy, a large proportion of patients with eGFR≥60 will already have moderate/severe TID. New biomarkers to aid in the early identification of these patients are needed. Clinically, mild impairment in eGFR may aid the decision to biopsy earlier for prompt detection of tubular damage.

References

Yu F, et al. Kidney Int 2010;77:820-9

R. Clark, et al. Semin Nephrol 2015; 35:455-464

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-variables-and-serologic-markers-of-disease-activity-do-not-aid-in-early-recognition-of-patients-with-tubulointerstitial-disease-who-have-no-significant-renal-impairment-at-time-of-biopsy/