#3191 RISK OF CKD IN LUPUS NEPHRITIS: CORRELATION WITH DURATION OF REMISSION AND DEVELOPMENT OF RENAL AND EXTRARENAL FLARES
Authors: Frontini Giulia , Quaglini Silvana , Gatto Mariele , Gasparotto Michela , Calatroni Marta , Reggiani Francesco , Cozzolino Mario Gennaro , Sinico Renato Alberto , Doria Andrea , Moroni Gabriella Luisa 
Published: June 2023

Abstract

Background and Aims
Achievement of remission and prevention of SLE flares are important therapy targets in patients with SLE in order to avoid the development of systemic chronic damage. In patients with lupus nephritis, the correlation between the duration of remission, the occurrence of SLE flares and the development of CKD is unclear. The aims of this study are to investigate a) the risk of CKD in patients with lupus nephritis b) the correlation between the risk of CKD and the development of renal and extrarenal SLE flares c) the correlation between the risk of CKD and the achievement and duration of remission d) the probability and predictors of renal and extrarenal remission.

Method
This is a retrospective multicentric study of prospectively collected data. Patients were included if they were &gt;18 years old, they had a histological diagnosis of lupus nephritis and they had at least 5 years of follow up after the diagnosis. CKD was defined as eGFR &lt;60 ml/min/1.73m2 without active urinary sediment for at least 3 months. Remission was defined as normal renal function (serum creatinine &lt;1.0 mg/dl, eGFR &gt;60 ml/min/1.73m2), proteinuria &lt;0.5 g/24h and cSLEDAI = 0 for at least 1 year. The probability of developing flares and achieving remission was estimated using Cox regression analysis.

Results
CKD developed in 57 patients out of the 303 included in the study (18.8%) during a median follow-up of 14.8 years. During the observation 257 patients achieved remission in a median time of 1.4 (0.7-3.6) years, while 46 patients never achieved it. 115 patients maintained remission until the end of follow-up (9.5 (5.8-14.5) years), while 142 developed a flare after a median time of 3.6 (2.3-5.9) years from the beginning of remission. Altogether, in these 142 patients, 174 SLE flares developed during a median follow-up of 17.8 (13.3-24.2) years: 132 renal flares (20 with serum creatinine increase, 112 with proteinuria) and 42 extra-renal flares. CKD developed in 11 patients with creatinine flares (55%), 19 patients with proteinuric flares (16.9%) and 1 patient with extra-renal flares (2.4%) (p&lt;0.0001). The longer was the duration of remission, the lower the probability that remission was interrupted (Figure 1A) by the development of a SLE flare: the risk of flare reduced from 10% when the remission lasted less than 5 years, to 5% if the remission lasted 5-10 years and to 2% if the remission lasted more than 10 years (Figure 1B). CKD developed in 26 out of the 46 patients who never achieved remission (56%), in 31 patients among those who achieved remission but developed SLE flares (21.8%) and in none among those who maintained remission until the end of the observation (p&lt;0.0001). We found that 3 years of persistent remission significantly reduced the risk of CKD development (Figure 2). At multivariate Cox regression analysis, age &gt;40 years (OR: 1.017; 95% CI: 1.005-1.028; p = 0.004), therapy with hydroxychloroquine (OR: 1.384; 95% CI: 1.109-1.661; p = 0.021) and absence of arterial hypertension (OR: 0.699; 95% CI: 0.425-0.975; p = 0.011) were independent predictors of remission.

Conclusion
in patients with lupus nephritis, the risk of CKD is significantly higher if renal-extrarenal remission is not achieved or if it is interrupted by SLE flares. In particular, the risk of CKD is very high in patients who develop renal flares with creatinine increase. A longer duration of remission is related to a lower risk of SLE flares and of CKD: in particular, 3 years of remission protect from the development of CKD. Age older than 40 years, therapy with hydroxychloroquine and absence of arterial hypertension are associated with the achievement of remission.