renal transplant

Post-Transplant LN Patients Can Have Viable Pregnancies

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Outcomes better in women with inactive systemic lupus erythematosus..

Having a renal transplant for lupus nephritis did not rule out successful pregnancies, but outcomes were better in those whose systemic lupus erythematosus (SLE) was inactive, according to an Italian case report.

The researchers, led by Gabriella Moroni, MD, of the Ospedale Maggiore IRCCS, in Milan, analyzed nine pregnancies in three of 38 women who had received kidney transplants at their center. Two patients had received a kidney from a living related donor and one had a received a transplant from a deceased donor.

From 2002 to 2013, five of these post-transplant pregnancies ended in miscarriage. All mothers were in their 30s by the time they conceived, and their initial pregnancies occurred at 4 years, more than 7 years, and almost 9 years after transplantation. In the last case, after two miscarriages, the woman had her first successful pregnancy more than 10 years’ post-transplant at age 38, the group wrote online in Lupus.

Miscarriages in transplanted patients are common, and preconception counseling is essential, the investigators noted.

“Women with stable and prolonged remission of SLE, normal renal function, normal blood pressure, and negative antiphospholipid antibodies (aPL) have good probabilities of positive fetal and maternal outcomes,” they explained.

However, they added that very few cases of post-transplant pregnancy in lupus nephritis (LN) patients have been reported in the literature.

In their study, patients were followed at least once a month and then followed twice weekly from 24 weeks’ gestation onward (including with serial placental Doppler imaging), hospitalized when necessary, and cared for by a multidisciplinary team of gynecologists and nephrologists.

All infants were delivered via cesarean, and the majority were of low birth rate, which may have been partly due to early surgical delivery, the authors explained. However, the infants were healthy and without serious complications, they added.

Immunosuppressive therapy consisted of steroids, calcineurin inhibitors, and mycophenolate mofetil (MMF), which had been replaced with azathioprine before conception. All patients had normal renal function and urinalysis (serum creatinine <1.5 mg/dL) and nonsignificant proteinuria (<500 mg/day). Some signs of immunological activity persisted after transplantation in two patients.

The authors stressed that before pregnancy, patients’ immunosuppressive regimens must be re-evaluated for possible teratogenic effects. They recommended switching from MMF to azathioprine. Also, ACE inhibitors must be discontinued before or at conception, they advised.

They reported that two pregnancies were uneventful. Pre-eclampsia occurred in a hypertensive patient in two pregnancies that ended in preterm delivery in one and newborns of small-for-gestational-age size in both. The authors ascribed these good results partly to the well-planned pregnancies and the specialized intensive care and imaging.

Significantly, although the risk of post-pregnancy graft loss in transplanted mothers is about around 6.9% within the first 5 years of giving birth, graft function continued to be normal in all patients. “To reduce such a risk it is wise to discourage pregnancy within the first year after transplantation,” they wrote. Urinalysis results also remained normal.

The authors noted that recent studies suggest that hydroxychloroquine improves obstetrical outcomes and should be part of immunosuppressive therapy throughout pregnancy.

“It is also important that patients start low-dose aspirin within the first trimester of pregnancy as primary prophylaxis for pre-eclampsia,” they cautioned.

Based on their experience and on published guidelines for renal transplanted patients, Moroni’s group concluded that “pregnancy in patients with kidney transplant due to LN should not be discouraged,” adding that “pre-conception counseling is mandatory.”

Prophylactic azithromycin helps avoid bronchiolitis obliterans in lung recipients

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Azithromycin is not only an effective treatment for bronchiolitis obliterans syndrome (BOS) after lung transplantation, it can also prevent the condition in the first place, a Belgian team reports in the European Respiratory Journal, online June 18.

“This paper is indeed one of the first randomized placebo controlled studies to prevent BOS after lung transplantation,” said senior investigator Dr. Geert M. Verleden at University Hospital Gasthuisberg, Leuven. “It clearly demonstrates that azithromycin in addition to current immunosuppressives is able to prevent BOS at least at 2 years after transplantation.”

Dr. Verleden and colleagues randomly assigned 83 lung transplant patients to either prophylactic azithromycin, 250 mg three times a week, or to placebo for 2 years.

BOS occurred in 12.5% of the patients on azithromycin compared with 44.2% in those given placebo. The hazard ratio for BOS-free survival was 0.27 (p=0.02) favoring azithromycin. The azithromycin group also had a greater forced expiratory volume in 1 second (FEV1).

However, rejection rates and overall survival were similar in the two groups.

“To us at least, this does not mean that every patient should now be treated with additional azithromycin, first of all since the results on survival are identical in the azi and the placebo group (because the ones who developed BOS were all shifted to active azithromycin),” Dr. Verleden said.

If patients are not treated prophylactically, “Of course then a close follow-up of the patients with pulmonary function testing and regular bronchoscopy with BAL (to look for neutrophilia) is then warranted. If this cannot be provided due to several logistic reasons, then we would advise to add (azithromycin) after transplantation ASAP.”

A second reason for not using azithromycin routinely is that the necessary duration of treatment is not known. “Whether azi has an effect later on (after more than 2 years) will have to be further investigated and currently we have one additional year of treatment in most of our patients but these data still need to be worked out,” Dr. Verleden continued.

His group has noticed that when azithromycin is started and then stopped later on, BOS may recur, Dr. Verleden said. “We do have patients who are taking azithromycin already for 8 years without any problems,” he added.