Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). In recent years, the morbidity and mortality of LN have improved considerably owing to more appropriate use of traditional drugs, such as corticosteroids and cyclophosphamide, and the incorporation of new ones, such as mycophenolate mofetil and biologic agents. Renal relapses are part of the natural history of LN and represent a significant challenge not only because they are associated with an increased risk of decline in renal function, but also there is a cumulative toxicity of immunosuppressive treatments.
Objectives The aim of this study was to review renal flare frequency, to identify potential risk factors for relapses, to assess the value of serological tests during flares and to analyse their impact on global outcome in LN patients.
Methods Patients with biopsy proven LN diagnosed between 1985 and 2015 were identified from our database. All patients (pts) met the ACR criteria for SLE. LN classes based on glomerular pathology were defined according to the ISN/RPS classification. Clinical and laboratory data were obtained from the records of patients. According to the response to treatment, LN pts were divided into 3 groups of complete remission (CR), partial remission (PR) and no response (NR). Those in remission were divided into 2 groups of relapsing and non-relapsing during maintenance period. Associated factors for remission and relapse were analyzed. CR was defined as proteinuria less than 0.5 g/24 h and stable or improved serum creatinine, whilst PR was defined as more than 50% reduction in baseline proteinuria achieving less than 1,0 g/24 h with stable or improved creatinine. We defined proteinuric flares as proteinuria above 1 g/24 h in pts with CR, and doubling of proteinuria in cases of PR.
Results 218 (70,64%) of 276 SLE pts (250 females and 26 males) with biopsy proven LN (class I ISN/RPS LN – 18 pts, class II – 45 pts, class III – 56 pts, class IV – 75 pts, class V – 54 pts, class VI – 2 pts, mixed forms – 26 pts) achieved either CR (n=154; 55,8%) or PR (n=64; 23,2%). 47 pts (38 had preceding CR and 9 had PR) with LN had one flare, 36 (26 had preceding CR and 10 - PR) – two flares, 27 (14 had preceding CR and 13 - PR) – three flares, 17 (7 had preceding CR and 10 - PR) ≥4 flares. The median time between remission and relapse was 23,5 ± 21,9 months in pts with CR, and 11,4 ± 9,3 months in pts with PR. The maintenance immunomodulating drugs at the time of flare was low dose (<10 mg/24 h) corticosteroids and/or azathioprine. 123 LN pts (48%) had angiotensin blockers in therapy. Non-adherence to treatment at time of relapse was documented in 26 pts. At the time of first flare, the median proteinuria was 1,84 ± 0,97 g/24 h in pts with CR, and 2,78 ± 1,25 g/24 h in pts with PR. 42 LN pts had raised serum creatinine, 65 had raised anti-double stranded deoxyribonucleic acid, 94 had low complements at flare.
Conclusions Renal flares in patients with LN are common, have a negative impact on outcome, but cannot be readily predicted. Our study shows that 58,83% of LN patients develop at least one relapse after reaching remission, usually within 2 years. The length of time to flare tends to be shorter in cases of preceding PR than in CR. Lack of adherence to long term immunosuppression was identified as a significant factor in LN flare (20,47%). Patients with LN in remission require close follow-up.
Disclosure of Interest None declared