Background Tubulointerstitial damage (TID) is associated with progression to end stage renal disease (ESRD) in lupus nephritis (LN)^1,2. However, it has not been established whether the association of TID and ESRD holds true in individuals with preserved or only moderately impaired renal function.

Objectives To determine if TID predicts progression to ESRD in LN patients with mild to moderate renal impairment at the time of kidney biopsy.

Methods We identified all adult and pediatric SLE patients (by ACR and/or SLICC criteria) who had an index biopsy consistent with LN between January 2005 and July 2015. Demographic data, comorbidities, medications, laboratory data, ESRD onset, and deaths through December 2015 were ascertained from medical chart reviews, the United States Renal Data Systemic Report, and National Death Index. Renal impairment was defined as mild (chronic kidney disease [CKD] stage 1 or 2, estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73m²), or moderate (CKD stage 2, eGFR≥30 and <60 mL/min/1.73m²). TID was defined as the presence of moderate to severe tubular atrophy and/or interstitial fibrosis as reported on the renal biopsies in accordance with the 2003 ISN/RPS criteria. Time to ESRD onset 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. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate whether TID was predictive of ESRD progression adjusting for eGFR (as a continuous variable) and LN class.

Results Of the 131 LN patients with mild to moderate renal impairment (8 (6%) Class II, 58 (44%) Class III/IV, 38 (29%) Class V, and 27 (21%) mixed), 16 (12%) progressed to ESRD. Eighty six percent of ESRD progressors had proliferative or mixed LN vs. 51% of non-ESRD, p=0.02. There were no significant differences with respect to age, sex, race, comorbidity scores, complement levels, anti-dsDNA, or protein to creatinine ratio at index biopsy between ESRD and non-ESRD groups. Median (IQR) baseline eGFR was 65 (51, 75) mL/min/1.73m² in the ESRD group and 97 (69, 127) mL/min/1.73m² in the non-ESRD group, p=0.001. TID was present in 12% of biopsies with eGFR≥60 mL/min/1.73m² and in 35% of biopsies with GFR between 30 and 60 mL/min/1.73m². Moderate to severe TID was associated with a high risk of ESRD progression (Figure 1, log-rank p-value<0.001), HR=8.3, 95% CI: (2.6, 27), p-value<0.001, adjusted for eGFR and proliferative or mixed LN. Similarly, TID remained a significant predictor when the analyses were limited to patients with a eGFR>60 mL/min/1.73m², HR=5.6, 95% CI: (1.3, 22.9), p=0.02, adjusted for eGFR.

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Conclusions TID was found in a significant proportion of clinically-indicated kidney biopsies in LN patients with mild to moderate renal impairment. The presence of TID was a strong predictor of ESRD progression in these patient independent of eGFR or biopsy class. Further studies are needed to identify factors associated with the presence of TID to develop effective prevention strategies.

1. Hsieh C, et al. Arthritis Care & Research Vol.63, No. 6, June 2011, pp 865–874.

2. Yu F, et al. Kidney Int 2010; 77:820–829.

Disclosure of Interest None declared