LONDON — The prognosis for patients with lupus nephritis who undergo renal transplantation today is good, with a low risk of recurrent renal flare and a decrease in lupus disease activity, Jo H. Berden, M.D., said at the Sixth European Lupus Meeting.
Uncertainty has existed as to whether outcomes among patients with systemic lupus erythematosus (SLE) would be equivalent to those seen among patients whose end-stage renal disease derives from another cause; studies have shown conflicting results and have been limited by confounding factors.
But a more comprehensive review of the European and U.S. experience has found no differences in graft or patient survival between lupus and nonlupus transplant recipients, said Dr. Berden of Radboud University, Nijmegen, the Netherlands.
An analysis based on European data for the years 1984 through 1992 provided by the Eurotransplant International Foundation, Leiden, the Netherlands, found no differences in either patient or graft survival when 165 lupus patients were compared with 20,000 nonlupus controls, Dr. Berden said at the meeting sponsored by the British Society for Rheumatology.
A larger analysis of data from the United States Renal Data System included 772 cadaveric transplants for lupus nephritis and 32,644 cadaveric transplants for other causes. This review also analyzed data from 390 lupus patients whose transplants had been from living donors and from 10,512 nonlupus patients whose transplants had been from living donors.
In an unadjusted analysis, patient survival was better in the lupus group, but graft survival was worse. Once adjustments were made for important confounding factors such as age and gender, however, there were no differences (Kidney Int. 2000;57:2136-43).
Nonlupus patients requiring renal transplantation tend to be male and older than the predominantly female lupus patients with this requirement.
Following transplantation, the incidence of renal flare in lupus patients is reported to be 2%-4% if clinical criteria are used and slightly higher if histologic criteria are used. This is a rather low incidence of recurrence, compared with that for other diseases, the nephrologist said.
Renal transplantation also confers nonrenal benefits to SLE patients. “In the Dutch Working Party on SLE, we found that most patients had severe disease before dialysis, intermediate disease during dialysis, and no extrarenal disease at all after transplantation. Apparently immune suppression that failed to control the disease initially was able to do so post transplantation,” he said.
The immunosuppressive regimen used for lupus patients after transplantation should take into account the heightened risk for cardiovascular disease in these patients, Dr. Berden cautioned. Among the immunosuppressant drugs, some, particularly cyclosporine, increase blood pressure. Sirolimus and cyclosporine raise cholesterol levels; tacrolimus and prednisone can induce or aggravate diabetes. In contrast, mycophenolate mofetil and azathioprine have little if any effect on blood pressure, cholesterol, or glucose levels. The long-term maintenance phase of immune suppression should therefore include one of these two less atherogenic agents, he said.
Experience also has taught that a careful evaluation before transplantation is essential for achieving the best outcome. “We screen all our candidates … for the presence of coronary abnormalities, even if there are no clinical symptoms,” he said. Because the exercise electrocardiogram is not sufficiently sensitive, a thallium scan or stress echocardiogram is recommended. “Until recently, we also did coronary angiography and if abnormalities were seen, revascularization was done,” he said. But recently a randomized clinical trial found no benefit for elective revascularization in asymptomatic patients awaiting major vascular surgery (N. Engl. J. Med. 2004;351:2795-804). “Therefore, there now is a question mark as to whether we should always advise revascularization,” he said.
Antiphospholipid antibodies, which are present in approximately one-third of lupus patients, present another unresolved issue. These antibodies signals an increased risk for acute graft thrombosis, so it remains unclear whether prolonged anticoagulation is needed following transplantation because there have been no randomized trials addressing this issue.
As with any patient approaching end-stage renal failure, “we should always consider preemptive living transplantation because the results are much better,” he said.