Predicting Lupus Flares: Could kidney biopsy be the key?
01.03.2019 from MedPage Today by Julie Maurer
Confirming that lupus patients are in remission and deciding when to stop immunosuppression therapy is a difficult task for physicians because it is difficult to predict when flares can reoccur. Susan Knowles, MD, FACR, a rheumatologist at Carson Tahoe Health, Carson City, Nevada, recommends patients continue immunosuppressive therapy until their disease is in remission, which could be 2-3 years or longer. "In my experience most patients remain on therapy long term, although their treatment may be modified, and in many cases the dose of their medication may be reduced, or medications may be changed/de-escalated (use lower potency medication) if they are doing well," Knowles told MedPage
Arundathi Jayatilleke, MD, a rheumatologist with Drexel Medicine in Philadelphia, said the general practice is that rheumatologists will treat for an extended period of time after lupus remission. "I usually treat for at least 1 year and sometimes 2 years after remission before considering lowering immunosuppression, assuming that the patient has no new signs of a renal flare," she told MedPage Today in an email.
A study from the University of Buenos Aires, by Marcelo De Rosa, MD, and colleagues set out to determine if finding histological renal activity through biopsy in lupus patients could be a predictor of flares. Eligible patients for the prospective, observational study published in Kidney International had been in remission for at least 12 months and had received at least 36 months of immunosuppression therapy.
"Patients consented to a second kidney biopsy, were tapered off maintenance immunosuppression and were then followed prospectively. Forty-four patients were enrolled, and 36 completed the study. LN flares occurred in 11 patients, and 10 of these had residual histologic activity on the second biopsy," De Rosa and colleagues wrote. These results were unexpected. "I was surprised that many patients in total clinical remission still have proliferative histological activity on the renal biopsy," De Rosa told MedPage Today in an email correspondence.
The results showed that a repeat kidney biopsy may be helpful to physicians in managing immunosuppression in lupus patients. "And patients in histologic remission may be candidates for withdrawal of therapy," De Rosa wrote.
Reactions to the study
Knowles said it is sometimes difficult to tell if lupus patients are in complete remission rather than just showing a positive clinical response and improvement. "We primarily rely on laboratory results such as complements, serum creatinine, urine microscopy, and urine protein/creatinine ratio, as well as how the patient is doing clinically," Knowles said. "Most of the time, the patients want to avoid an invasive procedure like a kidney biopsy; however, it can provide helpful information, especially in a patient whom we are considering stopping their immunosuppressive treatment."
She added that lupus is a difficult disease to treat and is hesitant to withdraw a patient's treatment unless she is certain they are in remission.
Jayatilleke said this was a very interesting and provocative study. "I think it raises the question of whether a kidney biopsy should be done but has some limitations that I would consider before putting it into routine practice for my patients," she said.
One consideration is that a kidney biopsy is an invasive procedure which can be risky to patients, even though it is generally considered safe.
"If the procedure can be used to prevent flares, then it may be very worthwhile. However, while the authors have evidence that active inflammation on biopsy predicts later renal flares, they can't tell us whether those flares would have happened even if patients remained on medication (all of the patients in this study were tapered off medication)," Jayatilleke said.
She added that while patients with no inflammation did not flare, they may do so at a later time than the study examined. "In addition, many of these patients flared well over a year after withdrawal of maintenance medication," Jayatilleke said. "It's possible that a biopsy performed a year after stopping maintenance would give the same results and less medication exposure." Despite this, she noted this study is interesting in an area without a lot of guidance. "I imagine there will be follow up studies to address some of the questions above that may further influence practice," Jayatilleke said. "Ideally of course we would have some other marker (in the urine or blood) for kidney inflammation in lupus nephritis that we could check, but that's an area that researchers continue to explore."
Patrick H. Nachman, MD, division of Renal Diseases and Hypertension, University of Minnesota, wrote a commentary on the De Rosa study in the same issue of Kidney International, saw some of the same limitations that Jayatilleke mentioned, but noted that the study demonstrated the feasibility of sound per-protocol repeat biopsy. "This important study does not provide us with definitive answers on the utility of a repeat kidney biopsy to inform the decision of withdrawing immunosuppressive therapy after a period of clinically quiescent lupus nephritis, primarily because of the relatively small number of patients enrolled and of outcome events," Nachman said.
He said this likely affected the ability to detect differences between patients who had renal relapse and those who did not. "It also limits the ability to perform a detailed analysis of which histologic findings are the most predictive of subsequent risk of relapse," Nachman said.
Still, he noted that the study is a promising step forward. "Their results are invaluable in informing the design of future confirmatory studies, which may more completely assess the interpretation of repeat biopsies in lupus nephritis, hopefully in conjunction with other, noninvasive biomarkers of disease. Indeed, their study sets an example for studies in kidney diseases other than lupus nephritis," Nachman said.
De Rosa also hopes for future research on the topic. "I think this is a small study that could help in the design of future bigger studies, including the renal biopsy changes," De Rosa said.