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Fernanda Schober, MD and Will Pendergraft, MD, PhD just published an editorial in Lupus Science & Medicine in which they review a recent study of specific biomarkers in lupus nephritis and provide their expert opinions on the need for repeated kidney biopsies to help treat patients with lupus nephritis and also identify meaningful biomarkers that could predict disease development and response to therapy.

Treatment of patients with lupus nephritis can be difficult for physicians, as it isn’t always clear from the patient’s visible symptoms how severely the disease is affecting the kidneys.

While physicians can look at current indicators of disease taken from the patient’s blood, urine, or other bodily fluids, to get a measure of the disease activity, these biomarkers are not always reliable.

A kidney biopsy is the most dependable source to determine the treatment’s effectiveness, and the biopsy results are used to guide the physician in treating the patient. This procedure, while typically done early on to diagnose the disease, is not always done on a repeat basis at all hospitals.

The study that Drs. Schober and Pendergraft evaluated used repeated biopsies to monitor patients with lupus nephritis and compared biomarker profiles to biopsy findings. In their article, they propose that repeat biopsies could be a standard part of a treatment protocol for lupus patients, and that repeat biopsies could be done on a routine basis regardless of how well the patient is doing in order to assess for true disease remission.

Dr. Pendergraft, Assistant Professor of Medicine, said that lupus can become aggressive quite quickly and can be very difficult to treat.

“One of the big problems in lupus is that a patient with lupus nephritis can be doing well based on all of our standard clinical markers, but a kidney biopsy at that exact time can still reveal very active disease even though the patient has been treated extensively,” he said. In other words, the kidney biopsy can reveal tissue damage that isn’t evident from the patient’s outward symptoms.

Lupus nephritis is complicated and researchers are working to understand it better.
There are five classes of the disease in which different symptoms are present.

Dr. Schober, who is a Glomerulonephritis and Vasculitis Fellow at The UNC Kidney Center engaged in multiple studies there, explained that classes of lupus are different from stages, such as in cancer, where the stages follow a progression. In lupus, each class is distinct and requires treatment specific to the class.

“Most lupus nephritis studies examine Class III and IV. Very few studies have been able to look at Class V because this class only represents roughly 10-20% of lupus nephritis; however, we care for a large cohort of individuals with Class V here at UNC,” she said. Dr. Schober is currently trying to understand what separates individuals who have Lupus Nephritis Class V as compared to the other classes.

Dr. Schober is also heavily involved in a related, and extensive study, in which the results of 1,900 biopsies performed at UNC are being reviewed to understand risks and complications of the kidney biopsy procedure. This will likely be the largest biopsy report of its kind.

“We’re starting to look at 5 years worth of biopsy data at UNC. Some providers and patients would prefer to start treatment without a kidney biopsy because there’s a perceived risk of bleeding and infection,” said Dr. Schober.

Since the kidney biopsy is the most reliable method to gauge disease activity, the goal would be to identify what key factors make a biopsy risky by looking at complication rates and what kind of complications patients had.

“For the patients that had complications, were there possibly any predictable factors? Like were their platelets, which help with blood clotting, too low?” she said.

Patients with lupus nephritis typically see specialists in both rheumatology and nephrology, and this collaboration between two subspecialties in medicine at UNC is growing to improve patient care and education. UNC is currently participating in and recruiting patients for the four major international clinical trials in lupus nephritis.

Dr. Pendergraft is also running an observational study called “STOP SLE”, which analyzes gene expression profiles from multiple blood cell subtypes and urine cells collected over time from patients with lupus nephritis to see how well they respond to treatment on a molecular level. Dr. Pendergraft noted that this is “the first ever study to really do this on a broad scale longitudinally.” Once results are validated, his team hopes to continue the study in a larger group of patients across the United States and Europe.

Read the editorial, “A blissful future for lupus nephritis: harnessing repeat kidney biopsies to identify meaningful biomarkers of disease.”