Lupus Flares Common During Renal Replacement Therapy

Nicola M. Parry, DVM

October 08, 2015

In some patients with systemic lupus erythematosus (SLE) and end-stage renal disease (ESRD), extrarenal disease flares, and in particular hematological manifestations, continue during renal replacement therapy (RRT), according to a new study published online September 21 in Rheumatology.

The researchers also identified clinical predictors associated with an increased risk for flares, including anticardiolipin immunoglobulin M (IgM) positivity, lower C4 levels, a history of hematologic activity, younger age at the start of RRT, and azathioprine therapy before disease flares.

"We found that most disease flares (66%) occurred in the first 2 years of RRT, with only four flare episodes after the fifth year. This is in agreement with prior studies and suggests that the closest patient follow-up should be in the first years after starting dialysis," write Ana Barrera-Vargas, MD, from the Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, and colleagues.

"Our results also show that SLE activity at more than one level is common (48%) in each flare episode. The most frequent types were hematologic, mucocutaneous, and articular, which agrees with other studies."

Renal involvement in SLE occurs in 40% to 70% of patients, and even with optimal treatment, up to one third of patients with lupus nephritis develop ESRD and require RRT within 10 years of disease diagnosis.

Data are lacking on lupus disease activity in patients with RRT, and what data exist are controversial, according to the authors. Previous studies have suggested that the incidence of flares declines after patients begin dialysis. However, more recent data have demonstrated that lupus flares occur in more than 50% of individuals with ESRD, and higher rates of disease activity may also occur in a subset of patients after RRT begins.

Dr Barrera-Vargas and colleagues set out to identify risk factors for SLE flares in patients with ESRD who were receiving RRT.

The researchers performed a retrospective case-control study of 88 patients with lupus in a tertiary care hospital in Mexico City from 1993 to 2014. The study included individuals who fulfilled at least four 1997 American College of Rheumatology criteria for SLE, had ESRD, and had undergone at least 3 months of dialysis. The case group comprised 38 patients who had experienced any extrarenal flare episode after RRT (the group experienced a total of 50 flare episodes), and the control group was made up of 50 patients with SLE with ESRD who had not experienced flares. Patients with HIV infection, hepatitis virus infection, autoimmune diseases (except for antiphospholipid syndrome), neoplasia, or an organ transplant were excluded, as were those who were pregnant or for whom incomplete clinical information was available.

Forty-eight percent of flare episodes involved activity in at least two different organs or systems and typically comprised hematologic activity in association with other organ involvement. Hematologic (42%), mucocutaneous (38%), and articular (30%) disease manifestations were the most common.

After multivariate analysis of various parameters evaluated among patients in the case and control groups, independent risk factors for lupus disease flares included younger age at RRT start (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.88 - 0.96; P < .001), a history of hematologic manifestations (OR, 3.79; 95% CI, 1.05 - 13.7; P = .04), and anticardiolipin IgM positivity (OR, 4.39; 95% CI, 1.32 - 14.6; P = .02), as well as low complement C4 levels (OR, 9.7; 95% CI, 2.49 - 39.12; P = .001) and azathioprine therapy in the 3 months before disease flares (OR, 1.025; 95% CI, 1.004 - 1.046; P = .02).

Patients who experienced flares were also more likely to be male, to have lower lymphocyte counts, and to have undergone hemodialysis as their RRT modality; however, these variables did not represent independent risk factors after multivariate analysis.

These results differ from previous studies that either identified other independent risk factors (eg, a history of seizures) or did not find specific SLE activity to be associated with flares, the current study authors report. "One of the risk factors that has been consistent throughout different studies is younger age at the beginning of RRT," they add.

"In summary, our findings show that SLE patients with ESRD do not reach an indefinite disease remission, especially during the first 2 years after the start of RRT. Patients with a higher risk of flare are those with a history of haematologic activity, positive anti-cardiolipin IgM, younger age at the beginning of RRT and low C4 levels," the authors write.

"Patients with these characteristics should have a closer follow-up in order to detect and treat SLE flares in a timely manner," they conclude.

The authors have disclosed no relevant financial relationships.

Rheumatology. Published online September 21, 2015. Abstract

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