Background/Purpose

Renal involvement in systemic lupus erythematosus (SLE) is frequent, and a high percentage of patients (~15%) develop end-stage renal disease (ESRD) even with optimal treatment. It is widely supposed that ESRD in these patients leads to an indefinite remission period. Currently, information about SLE activity in patients with renal replacement therapy is quite scant. The aim of this study was to identify risk factors for SLE flares in patients with ESRD.

Methods

A retrospective, case-control study was performed in a tertiary care center in Mexico City from 1993 to 2014. Cases (n=50) were patients with SLE diagnosis (at least 4 American College of Rheumatology criteria) who had any extra-renal flare (any increase in systemic lupus erythematosus activity index –SLEDAI- score that required the modification of immunosuppressive treatment) after at least three months of renal replacement therapy (RRT). Controls (n=50) were patients with SLE and ESRD but without any flares, studied during the same period of time as cases (±3 months). Association between variables was calculated by X² test and OR (95% CI). Multivariate analysis was performed by logistic regression. p values less than 0.05 were considered statistically significant.

Results

There was a higher percentage of men in the case group (24 vs 8%, p=0.029). At the time of the SLE flare, patients had required dialysis for a mean period of 23.1±3.6 months. There was no difference in the time period between SLE diagnosis and the beginning of dialysis in both groups (p=0.06). Variables previous to the exacerbation which had significant differences in the univariate analysis are showed in Table 1. Variables that remained significant after multivariate analysis were: history of fever secondary to SLE [OR 3.20 95%CI 1.02-10.04, p=0.046], history of hematologic activity [OR 4.02 95%CI 1.02-15.79, p=0.046], low C4 levels prior to the flare [OR 19.62 95%CI 3.72-103.3,p<0.001], anticardiolipin IgM positivity [OR 4.32 95% CI 1.07-17.43, p=0.040], presence of lupus anticoagulant [OR 9.38 95% CI 1.26-69.79, p=0.029], age at the beginning of renal replacement therapy [OR 0.92 95%CI 0.88-0.96, p<0.001],and adjusted SLEDAI score (excluding renal items) three months prior to exacerbation [OR 0.57 95%CI 0.37-0.87, p=0.010].

Conclusion

Our findings suggest that immunologic parameters, such as low C4 levels and antiphospholipid antibodies might play a key role in predisposing to flares in patients with SLE and ESRD. Moreover, patients who initiate RRT at older age and who have had persistent disease activity are at a higher risk for extrarenal flares during follow-up.

Table 1.Variables associated with development of (univariate analysis)

 

Prior to exacerbation	OR	95% CI	p value
History of different types of activity
Hematologic       Hemolytic anemia       Persistent thrombocytopenia (˂150,000/uL)       Persistent leukopenia (˂3,000/uL)       Persistent lymphopenia (˂1,000/uL) Serositis	10.2 6.76 3.16 10.28 2.97 2.57	2.20-47.90 1.41-32.36 1.03-9.68 2.20-47.90 1.30-9.68 1.12-5.89	0.001 0.007 0.037 0.001 0.009 0.024
Previous Serology
Lupus anticoagulant        Anticardiolipin IgM        Low C4 levels	6.76 2.95 4.93	1.41-32.36 1.14-7.64 1.98-12.26	0.007 0.023 ˂0.001
Previous Treatment (Three months)
Azathioprine	13.82	1.71-111.72	0.002

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/novel-risk-factors-for-systemic-lupus-erythematosus-sle-flares-in-patients-with-end-stage-renal-disease-is-sle-in-patients-with-end-stage-renal-disease-a-sleeping-beauty/