Abnormal SLE Serology Need Not Bar Pregnancy

WASHINGTON, D.C.—Abnormal serology alone should not lead clinicians to advise against pregnancy when counseling women with systemic lupus erythematosus (SLE), even those with previous renal disease, according to a new prospective study presented at the American College of Rheumatology (ACR) annual meeting.

“Patients with past renal disease who are currently in partial or complete renal remission generally do not flare during pregnancy, even if they have persistently elevated anti-DNA and low complement levels,” said study investigator Jane Salmon, MD, Professor of Medicine at Weill Medical College of Cornell University in New York.

“This study is important because it supports the notion that if a lupus patient has never had renal disease, pregnancy, in and of itself, is not likely to increase that risk,” said co-investigator Jill Buyon, MD, Professor of Medicine at New York University School of Medicine.

Drs. Salmon and Buyon and colleagues conducted The PROMISSE Study (Predictors of pRegnancy Outcome: BioMarkers In antiphospholipid antibody Syndrome and Systemic Lupus Erythematosus), which prospectively evaluated 390 pregnant systemic lupus erythematosus patients. The investigators excluded women with multi-fetal pregnancy, taking prednisone at a dose greater than 20 mg/day, proteinuria greater than 1g/24 hr, and serum creatinine greater than 1.2 mg/dL. Overall, of the 390 patients completing pregnancy, 17% had only positive anti-dsDNA, 12% had only hypocomplementemia, 20% had both serologies, and 51% had neither serology at the time of enrollment. Of the 390 patients, 121 (31%) had preexisting renal disease as defined by ACR SLE criteria and/or a renal biopsy.

For the study, researchers defined a renal flare as an increase of at least 500 mg of protein per day with or without hematuria and/or red blood cell casts.  Sixteen patients of the 120 with past renal disease  experienced renal flares. All patients had proteinuria, five (31%) had hematuria, and one (6%) had red blood cell casts. However, the researchers found no differences among biopsy classes for patients with and without renal flares. Among 29 patients with a history of renal disease and both anti-dsDNA and hypocomplementemia, five (17%) had a renal flare.

In 44 patients with either anti-dsDNA or hypocomplementemia alone, seven (16%) had renal flares; in 47 patients with neither serology, four (9%) had renal flares. These slight trends toward a higher rate of renal flare in those patients with abnormal serologies did not reach statistical significance. In this cohort, five patients were treated with increased doses of prednisone. Three treated patients and two untreated patients developed preeclampsia.

Rheumatologists generally advise patients to be in remission for six months prior to pregnancy, Dr. Salmon said. From a renal standpoint, this generally means being in a partial or complete remission (a protein/creatinine ratio less than 1). In addition, patients on mycophenolate mofetil must be either switched to azathioprine or have immunosuppressive medications discontinued altogether. 

“One issue, which has been of concern for both rheumatologists and nephrologists, is whether the continued presence of serologic activity (positive anti-DNA antibodies and low complements) is a harbinger of a greater risk for renal flare,” Dr. Salmon said. “No previous study has specifically addressed this question, although it has been reported that hypocomplementemia can predict poor fetal and maternal outcomes. Some physicians caution patients against contemplating pregnancy until all laboratory aspects of lupus have returned to normal.”

Adverse pregnancy outcomes included three (19%) fetal/neonatal deaths and two (13%) with SGA below the 5th percentile in the 16 patients with renal flares. Only three renal flares occurred in the 270 patients with no history of kidney disease. Of the 50 patients with no history of renal disease and both anti-dsDNA and hypocomplementemia, two (4%) had new-onset proteinuria; preeclampsia developed in one of these patients. In 150 patients with neither serology, only one patient had new-onset proteinuria, which was treated. She had SGA below the 5th percentile. None of the 70 patients with either serology alone had renal flares.

Although limited by small sample size, the presence of anti-dsDNA and low complement levels or an abnormality in either test in pregnant patients with previous nephritis and current remission, did not associate with a statistically higher risk of renal flare than those with normal analyte values.

Dr. Buyon summed up the data by noting that “this large multicenter, multiethnic prospective study provides reassurances for physicians counseling patients with previous renal disease. In agreement with available literature, patients in complete or partial remission have a low risk of renal flare even in the presence of abnormal serologies. Advising against pregnancy for those with persistent serologic activity but clinical quiescence is probably not warranted but given the trends observed may require further study.” 

In this study, the good news is that increased proteinuria only occurred in 13% of patients with previous renal disease and 1% of those without a history of kidney disease, she added.

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