Comparison of complete renal response and mortality in early- and late-onset lupus nephritis: a multicenter retrospective study of a Japanese cohort

Abstract

Background: Most patients with systemic lupus erythematosus (SLE) progress to lupus nephritis (LN) within 5 years of their SLE diagnosis, although it is not uncommon for LN to develop at later time points. Here we evaluated the clinical features of early-and late-onset LN. Patients and methods: We retrospectively analyzed the cases of 184 of the 201 patients who underwent a renal biopsy at Nagasaki University Hospital and associated community hospitals between 1990 and 2016 and were diagnosed as having LN. Early onset was defined as the development of LN within the first 5 years after the patient's SLE diagnosis, and late onset was defined as LN development > 5 years post-diagnosis. We analyzed the complete renal response (CR) at 6 and 12 months after induction therapy, the classification of renal pathology, and the mortality of the early-and late-onset LN groups. Results: The mean follow-up duration after the renal biopsy was 123 ± 85 months. There were 113 (61.4%) early-onset patients and 71 (38.6%) late-onset patients. A multivariate analysis revealed that the following factors were predictive of CR: at 6 months: female sex (odds ratio [OR] 3.93, 95% confidence interval [CI] 1.31-11.77, p = 0.010), proteinuria (OR 0.83, 95% CI 0.71-0.97, p = 0.009), index of activity (0-24) (OR 0.83, 95% CI 0.70-0.99, p = 0.030), and early-onset LN (OR 2.39, 95% CI 1.15-4.98, p = 0.018); at 12 months: female sex (OR 3.60, 95% CI 1.32-9.83, p = 0.013), mixed LN (OR 0.18, 95% CI 0.04-0.80, p = 0.024), index of activity (0-24) (OR 0.80, 95% CI 0.68-0.94, p = 0.007), and early-onset LN (OR 2.10, 95% CI 1.05-4.23, p = 0.035). In a Cox proportional hazards and Fine-Gray regression model, the early-onset LN group had a significantly better mortality rate than the late-onset LN group (p = 0.038 and p = 0.043, respectively). Conclusions: In our cohort, early-onset LN was a better predictor of CR at 6 and 12 months than late-onset LN. Our results suggest that early-onset LN patients had lower mortality than late-onset LN patients.

Comparison of renal remission and relapse‐free rate in initial‐ and delayed‐onset lupus nephritis

“…Ichinose et al previously reported that the early‐onset LN group was characterized by higher levels of anti‐dsDNA antibodies and hypocomplementemia with higher serological activity, and a lower index of chronicity compared to the late‐onset group. 22 Park et al reported that glomerular sclerosis in the chronicity index was an independent predictor of complete remission after start of therapy in LN patients. 25 In addition, it was difficult to calculate and compare the chronicity index due to the different historical backgrounds and organized evaluators.…”

“…Second, due to the retrospective nature of the study, heterogeneity in LN patients could not be fully excluded, which has been reported as a limitation with retrospective observational studies on LN. 21 , 22 , 30 Owing to the long study duration, the treatment regimen for LN varied based on time, and because many physicians treated patients in this study, treatment regimens were subtly different for each treating physician. Additionally, because we did not store serum samples from patients, we could not measure several biomarkers that are useful for determining the pathophysiology of LN.…”

“…Finally, it was difficult to define patients with delayed‐onset LN, and we defined such patients as those who were diagnosed with LN at ≥12 months after SLE diagnosis and who had already achieved remission of SLE before being diagnosed with LN. Although Jacobsen et al 16 and Seligman et al 17 reported that renal manifestation in most patients with SLE was observed within a year; several studies 15 , 19 , 22 have defined delayed‐onset LN based on a time gap of 5 years between SLE diagnosis and LN development. Therefore, it could not be ruled out that the patients with delayed‐onset LN in this study might have included several patients with initial‐onset LN.…”

“…On the other hand, several reports from Japan showed that SLE patients with early‐onset LN had better renal outcomes when compared to those with late delayed‐onset LN. 18 , 21 , 22 Because the results were different, it is unclear how the timing of LN onset affects its pathophysiology. Although a renal biopsy is recommended for diagnosing and treating LN, it is difficult to achieve in patients at risk of bleeding, in poor general condition, or who refuse it.…”

Differences and similarities of proliferative and non-proliferative forms of biopsy-proven lupus nephritis: Single centre, cross-disciplinary experience

“… 7 – 10 Early-onset LN, female gender, absence of renal exacerbation, and anti-SSB antibodies have been reported as positive predictors for complete renal response. 7 , 11 …”