#4928 CLINICAL AND HISTOLOGICAL CHARACTERISTICS AND LONG-TERM PROGNOSIS OF LATE-ONSET LUPUS NEPHRITIS
Authors: Shabaka Amir , Mendoza Ana , Rodriguez-Moreno Antolina , Pamplona Irene Agraz , Rabasco Cristina , Procaccini Fabio , Cuellar Hernando Trujillo , Malek Tamara , Hadad-Arrascue Fernando , Cobelo Carmen , Gueorguieva Antonia , Sierra Milagros , Serrano Mariana Garbiras , Juarez Gema Maria Fernandez 
Published: June 2023

Abstract

Background and Aims
Systemic lupus erythematosus (SLE) occurs mainly occurs in young women of child-bearing age and is not commonly found in the elderly population. Several studies suggest that the age at the onset of the disease has an influence on the course and the prognosis of the disease. Some studies have described that an early onset of lupus nephritis (LN) has a worse prognosis than a late-onset, presenting with greater complications and higher mortality, whereas other studies have shown that late-onset SLE present higher rate of organ damage and mortality. There are no series of late-onset LN that have been described in a European population to date. The KDIGO guidelines do not distinguish early from late-onset LN regarding their immunosuppression strategy recommendations The objective of this study was to compare the presentation, course and outcomes of late-onset LN compared to early-onset LN in a Spanish population, and detect differences in outcomes according to treatment received.

Method
We performed an observational retrospective multicenter study that included adult patients who developed LN confirmed by a kidney biopsy after the age of 50 years, defined as late-onset LN. We compared them to a group of selected patients aged younger than 50 years at the diagnosis (early-onset LN), matched for disease duration. Baseline demographic, clinical, serological and histological characteristics were compared between both groups. We compared the course of the disease in both groups including renal flares, serious adverse effects, and a composite outcome defined as doubling serum creatinine, developing end-stage kidney disease and/or death. Cox regression analysis was used to examine the association between late-onset LN and its outcomes.

Results
The study included 229 patients; 67 with late-onset LN and 162 early-onset LN patients. Late-onset LN patients presented more frequently hypertension (p&lt;0.001) and diabetes (p = 0.008). There was a lower frequency of cutaneous manifestations (p &lt;0.001) and oral ulcers (p = 0.008), higher frequency of hematological manifestations (p = 0.015) and Sjogren syndrome (p = 0.05). Patents with late-onset LN showed a worse baseline kidney function (p&lt;0.001) and higher serum complement levels (p&lt;0.001). Late-onset LN patients showed higher chronicity indices in kidney biopsies, with more glomerulosclerosis (p = 0.003), interstitial fibrosis (p = 0.021) and tubular atrophy (p = 0.011). There were no differences in the distribution of LN histological classification between both groups. We did not find significant differences between early and late-onset LN as regards induction and maintenance immunosuppression therapies, showing only a lower rate of antimalarial drug use in late-onset LN as maintenance therapy (p = 0.001). After a median follow-up of 7.4 (2.8-13) years, patients with late-onset LN showed a lower number of flares (p = 0.015), and a higher rate of serious adverse events related to immunosuppression, particularly infectious complications (34.3% vs 18.5%, p = 0.01). There were no differences in complete or partial remission or kidney function between both groups at the end of follow-up, however mortality was higher in late-onset LN patients, developing more frequently the composite outcome (19.4% vs 8%, p = 0.014). No significant difference was found in kidney survival (log-rank chi-square = 2.09, p = 0.148). Cox regression analysis showed that late-onset LN (hazard ratio = 3.26, 95% CI 1.18-8.98, p = 0.02), % sclerosed glomeruli (HR = 1.03, 95% CI 1.01-1.06, P = 0.019) and presence of severe side effects related to immunosuppression (HR = 10.09, 95% CI 3.2-31.7, p&lt;0.001) were independent risk factors for reaching the composite outcome.

Conclusion
Although patients with late-onset LN present with worse kidney function and more severe chronic lesions in kidney biopsy, they show comparable kidney outcomes to patients with early-onset LN, and despite receiving similar immunosuppressive regimens they develop less renal flares but more serious adverse events, leading to a worse overall outcome. Minimization of immunosuppression regimens in late-onset LN may be an adequate option to improve patient outcomes.