LUPUS NEPHRITIS IS ASSOCIATED WITH MORE CORTICOSTEROID-ASSOCIATED ORGAN DAMAGE BUT LESS CORTICOSTEROID NON-ASSOCIATED ORGAN DAMAGE

Abstract

Background Lupus nephritis (LN), one of the most serious manifestations of systemic lupus erythematosus (SLE), has been suggested to be a predictor of organ damage accrual. Also, LN is considered a strong determinant for survival. Since patients with LN are more exposed to immunosuppressive agents, such as cyclophosphamide and high-dose corticosteroid, and also have high inflammatory burdens, they might be more vulnerable to organ damage than patients without LN. Thus, proper adjustment for these potentially confounding variables needs to be performed to determine the precise effect of LN on organ damage. Also, it is important to identify the types of organ damage that are associated with LN. However, these aspects have not been previously investigated.

Objectives We investigated the impact of LN on organ damage accrual and mortality after adjusting for potential confounders. In particular, we identified the types of organ damage that are more or less associated with LN.

Methods Patients with SLE were propectively enrolled and followed from 198 to 2012 in the Hanyang BAE Lupus cohort. LN was defined as the disorder with the persistent proteinuria greater than 0.5 grams per day Organ damage was assessed using SLICC/ACR Damage Index (SDI). Damage presumed to be corticosteroid associated (cataract, avascular necrosis, diabetes and osteoporosis items) and non-associated (5 pulmonary, 5 gastrointestinal, erosive arthritis, 3 skin, premature gonadal failure and malignancy items) selected from 41 items were compared. Association of LN with organ damage was analyzed using multivariable logistic regression analysis, adjusting for potential confounders. Age- and sex adjusted standardized mortality ratio (SMR) was evaluated in patients with or without LN.

Results Among the 1,112 SLE patients, 515 (46.3%) had LN. Patients with LN showed higher percentage of male (p=0.003), were younger at diagnosis (p<0.001), had longer disease duration (p<0.001), higher adjusted mean SLE Disease Activity Index (AMS) score (p<0.001), lower percentage of prescribed anti-malarial agents (p<0.001), and higher percentage of corticosteroids (p<0.001) and immunosuppressant use.

After mean follow-up of 7.6 years, patients with LN had higher percentage of overall organ damage than patients without LN (51.5% vs 35.7%, p<0.001) with OR of 1.40, after adjusting for age at diagnosis, gender, disease duration, anti-malarial agents, corticosteroids and immunosuppressant. However, LN was not associated with non-renal organ damage (p=0.883). In subgroup analysis, the odds of corticosteroid-associated damage was higher in patients with LN (2.06, 95% CI 1.43–2.96), but whereas odds of non-associated damage was lower in patients with LN (0.50, 95% CI 0.35–0.75), compared not having LN.

Age- and sex adjusted SMR of patients with LN was 5.17 (95% CI 3.49–7.38) and 2.32 (95% CI 1.47–3.48) in patients without LN.

Conclusions LN was associated with more overall organ damage but not more non-renal organ damage. Patients with LN had more corticosteroid-associated damage, but less corticosteroid non-associated damage compared with patients without LN. Additionally, the SMR of patients with LN was significantly higher than the SMR of patients without LN