Abstract
Background
Lupus nephritis (LN) is one of the most serious complications of systemic lupuserythematosus (SLE).Immunosuppression (IS) is the standard of care therapy for lupusnephritis(LN).Data on the outcomes of LN patients after discontinuation ofimmunosuppression remain uncertain.
Objectives
To assess the outcomes of patients with LN after discontinuation of immunosuppression.
Methods
Clinical and laboratory data were retrospectively collected on LN patients attending our Lupus Unit.We included 45 patients(41had biopsy confirmedLN)who were treated with immunosuppression including cyclophosphamide, mycophenolate, azathioprine,methotrexate, and/or rituximab.Numeric response variables(median and range)including age, disease duration and length of treatment were collected.Frequencies and percentages categorical variables including gender, ethnicity, lupus nephritis class, autoantibodies, laboratory features, IS therapy used and patients’ outcomes (stable versus flared) were analysed.LN flares were defined as: doubling of serum creatinine concentrations and increases in proteinuria after discontinuation of IS.Chi-square tests were applied to comparethese categorical variables between patient’s outcomes.Reasons for IS discontinuation: remission, pregnancy planning and patients preference.
Results
We identified the outcomes of 45LN patients who stopped IS therapy.The median age of patients was 55(29 -78)years. The median durationof diseasewas 26.5(15-58)years whereas the median treatment duration was 4(1/2-14)years.Thirty (66.7%)patients were Caucasian ethnicity.Seventeen of 45patients received treatment for more than 5 years.There was only 1(2.2%)male patient in our study. At IS discontinuation, creatinine levels were elevated in9/45 (2%) patient and median creatinine values were 73(41-117umol/L).Median proteinuria values were 20mg/mmol (5-934)(p=0.00).LN histology: classV(24.4%),IV 17.8%and III(17.8%)and eleven patients had a combination of class III IV. Thirteen of 45 (28.9%)patients had relapses after discontinuation of IS. Median time to LN flare was 3(1-17) years and median age of the flared patients was58 years(41-70)years.Median creatinine values and median proteinuria of the flared patients were78(41-111umol/L),361.5 mg/mmol(12-908)respectively.Of these 13relapsed LN patients,4had class III,4had class V and the other patients had combinations of classes.Anti-Sm antibodies were more likely to be associated with relapses(6 patients) compared to stable patients(4 patients)(6% vs.40%) (p=0.030).Anti-
dsDNA
antibodies were positive in 22/32 stable patients(68.8%)compared to 10/13(31.3%)relapsed patients (p=NS).Among 13flared patients, 5 (38.5%)had high creatinine levels and 8(61.5%)had normal serum creatinines(p=0.048)on discontinuation of IS. Of 45 patients,12 had low complement C3, of whom 7(58.3 %) flared and 5(41.7%) were stable(p=0.009).Similarly, of 12patients with lowC4, 8(66.7%)flared compared to 4with stable outcomes(33.3%)p=0.001 .A higher proportion of patients previously taking azathioprine relapsed compared to those with previous use of cyclophosphamide or MMF 30.8%vs15.4%(p=0.011)respectively.
Conclusion
Our data suggests that two thirds of our patients experienced clinical remission with stable LN following cessation of IS therapy for LN.Patients who had elevated serum creatinine values, persistent proteinuria, low complement, positive anti Sm antibodies and previous azathioprine use were more likely to flare after stopping IS.Anti-
dsDNA
antibodies levels did not predict flares after stopping IS.Further prospective studies with larger sample sizes and longer follow-up are needed to estimate LN outcomes after discontinuation of immunosuppression.
Table 1.
Patient’s characteristics and lupus nephritis outcome
Parameters n (%)
Flared patients(N=13)
Stable patients(N=32)
P value
Abnormal creatinine
5(55.6%)
4(44.4%)
0.048
Significant UPCR
8(88.9%)
1(11.1)
0.000
Anti-sm
6(60%)
4(40%)
0.030
Low C3
7(58.3%)
5(41.7%)
0.009
Low C4
8(66.7%)
4(33.3%)
0.001
Disclosure of Interests
None declared