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Abstract
Background We previously reported different clinical features, serological profiles and activities in two onset categories of lupus nephritis (LN): LN that developed as a flare of systemic lupus erythematosus (SLE) after treating the prior non-renal SLE conditions successfully (delayed, D-LN) and LN manifesting at the time of SLE onset (early, E-LN).1) More frequent flares and higher serum titers of anti-dsDNA antibody during the LN flares were observed in D-LN than E-LN groups, suggesting that D-LN may reflect intractable SLE conditions. However, we had not analyzed whether there is a difference in the response to treatment between the two groups.
Objectives This study investigated possible differences in the response to induction therapy between E-LN and D-LN.
Methods We retrospectively examined 95 LN (48 E-LN, 47 D-LN) patients who attended our hospital between January 1991 and May 2016. All of them were diagnosed with SLE according to the American College of Rheumatology criteria and were shown to have LN on renal biopsy. First, we compared the clinical features of E-LN and D-LN, such as sex, age at SLE and LN onset, urinary protein, serum creatinine, serum anti-dsDNA titer, serum C3, prevalence of serum anti-Sm, renal biopsy histological types and induction therapy options at LN onset. Then we compared the response to therapy at 24 weeks for LN onset and flares between the two groups. The response to treatment was classified into complete response [CR; urine protein to creatinine ratio <50 mg/mmol and normal or near-normal (within 10%)GFR], partial response [PR; ≥50% reduction in proteinuria to sub-nephrotic levels and (near-) normal GFR], and insufficient response [IR; anything else]. We analyzed the data using chi-square test, Fisher's exact test and the Mann–Whitney U-test. We further evaluated predictors of treatment response at LN onset using univariate and forward stepwise multivariate Cox regression analysis.
Results Higher serum C3 (56.4±22.4 vs. 46.3±22.7 mg/dl, p=0.03) were observed in D-LN groups. The proportion of histological types (I or II/III or III+V/IV or IV+V/V: 6/7/26/9 vs. 4/5/26/12, p=0.77) and induction therapy options at LN onset were similar between the two groups. However, the response to the therapy for LN onset was better in E-LN than D-LN (CR/PR/IR: 37/10/1 vs. 24/17/6, p=0.02) (Fig). Univariate Cox regression analysis indicated that severe proteinuria, elevated serum creatinine, class IV or IV+V on renal biopsy and D-LN were associated with non-CR (PR+IR) to induction therapy for LN onset (p<0.05). Multivariate Cox regression analysis including variables identified as significant in univariate analyses showed that severe proteinuria [hazard ratio (HR) 1.35, p=0.007] and D-LN [HR 4.96, p=0.003] were independent predictors of non-CR to the induction therapy. LN flares were observed in 13/48 E-LN and 20/47 D-LN patients, and IR was observed in 15.4% (2/13) of E-LN and 40.0% (8/20) of D-LN patients.
Conclusions In this study, the relatively poorer treatment response was observed in D-LN compared with E-LN patients and D-LN was a predictor of poorer treatment response independent of renal histology and the severity of nephritis at LN onset.
References
Nakano M, et al. Different clinical features, serological profiles and activities in two onset categories of lupus nephritis. EULAR 2016 congress London, SAT 0313.
References
Disclosure of Interest None declared