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

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

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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

Of the 201 enrolled patients, a total of 184 patients could be followed for therapeutic response at 6 and 12 months after their induction therapy (Fig. 1).

Predictors of CR at 6 months and 12 months after induction therapy

The predictors of a CR at 6 and 12 months after induction therapy in the univariate and multivariate analyses are shown in Tables 1 and 2, respectively.  In the multivariate regression analysis, the independent predictors of a CR at 6 months after induction therapy were female sex (odds ratio [OR] 3.93, 95% condence interval [CI] 1.31–11.77, p=0.010), proteinuria (g/gCr) (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). The independent predictors of a CR at 12 months after induction therapy were 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).

The renal survival rate and survival rate: early-onset vs. late-onset LN

Seven patients (3.8%) progressed to ESKD, and nine patients (4.9%) died during the observation period. The 1-KM (Kaplan-Meier analysis estimate) and competing risk analysis showed that the cumulative incidence of ESKD was not significantly different between the early-onset LN group and late-onset LN group (p= 0.725 and p = 0.575, respectively) (Fig. 2), whereas the cumulative incidence of mortality difiered significantly between the early- and late-onset LN groups (p = 0.031 and p = 0.040, respectively) (Fig. 3).

Conclusions

In the cohort, analyses revealed that early-onset LN, female sex, and a lower index of activity (0–24) were the factors most predictive of CR aainment at both 6 and 12 months. Early-onset LN was associated with lower mortality than late-onset LN patients. We need to further investigate the factors that worsen treatment response and mortality in patients with late-onset LN.

References

1. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110–21.

2. Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7.

3. Parikh SV, Almaani S, Brodsky S, Rovin BH. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis; 2020. in press.

4. Varela DC, Quintana G, Somers EC, Rojas-Villarraga A, Espinosa G, Hincapie ME, Anaya JM. Delayed lupus nephritis. Ann Rheum Dis. 2008;67(7):1044–6.

5. Kanda Y. Investigation of the freely available easy-to-use soware ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.

6. Wang YF, Xu YX, Tan Y, Yu F, Zhao MH. Clinicopathological characteristics and outcomes of male lupus nephritis in China. Lupus. 2012;21(13):1472–81.

7. Imran TF, Yick F, Verma S, Estiverne C, Ogbonnaya-Odor C, Reddi AS, Kothari N. Lupus nephritis: an update. Clin Exp Nephrol. 2016;20(1):1–13.

8. Park DJ, Choi SE, Xu H, Kang JH, Lee KE, Lee JS, Choi YD, Lee SS. Chronicity index, especially glomerular sclerosis, is the most powerful predictor of renal response following immunosuppressive treatment in patients with lupus nephritis. Int J Rheum Dis. 2018;21(2):458–67.

9. Malvar A, Pirruccio P, Alberton V, Lococo B, Recalde C, Fazini B, Nagaraja H, Indrakanti D, Rovin BH.. 2017;32(8):1338–44.

10. Moroni G, Vercelloni PG, Quaglini S, Gao M, Gianfreda D, Sacchi L, Raoa F, Zen M, Costantini G, Urban ML, et al. Ann Rheum Dis. 2018;77(9):1318–25.

11. Nakano M, Kubo K, Shirota Y, Iwasaki Y, Takahashi Y, Igari T, Inaba Y, Takeshima Y, Tateishi S, Yamashita H, et al. Lupus. 2019;28(9):1062–73.

12. Ichinose K, Kitamura M, Sato S, Eguchi M, Okamoto M, Endo Y, Tsuji S, Takatani A, Shimizu T, Umeda M, et al. Lupus. 2019;28(4):501–9.