Lupus nephritis should be treated promptly, without waiting for kidney biopsy results — but that does not mean a biopsy should be dismissed altogether. That was the central message of the ReumaFights panel, a debate-style session with opposing viewpoints at the 43rd Brazilian Congress of Rheumatology, held September 2-5 in Curitiba, Brazil.

When the audience was asked, “Do we always need a renal biopsy in lupus nephritis?” the overwhelming response was “yes.” But the two physicians leading the discussion ultimately agreed that “always” is not the right word in this setting.

On one side, Evandro Mendes Klumb, PhD, a member of the Lupus Committee of the Brazilian Society of Rheumatology (SBR) and coordinator of the Rheumatology Unit at the Rio de Janeiro State University in Rio de Janeiro, Brazil, argued that treatment cannot wait for the biopsy. On the other hand, Edgard Torres dos Reis Neto, MD, PhD, an adjunct professor of rheumatology at the Paulista School of Medicine of the Federal University of São Paulo in São Paulo, Brazil, and a member of the Lupus Commission of SBR, argued by highlighting the importance of the procedure and the need to overcome the challenges of accessing it.

“In fact, there is no 100% correct answer — that is, we perform a biopsy whenever possible, but we cannot wait for the biopsy results to begin treatment,” summarized Klumb in an interview with Medscape’s Portuguese edition shortly after the panel discussion.

For Klumb, the principle guiding his practice is simple: “Treatment is immediate; a biopsy is not.” He argued that clinical data alone are not sufficiently reliable for accurately determining histologic class and that waiting for pathologic confirmation can jeopardize kidney function.

“The accuracy of class inference is flawed, and one can — and should — actually start treatment first and then do the biopsy because we’re talking about a young person’s kidney,” he said. “I wouldn’t treat cancer without a precise diagnosis, and if cancer is suspected, I have to do a biopsy. But in lupus nephritis, we should begin treatment and, whenever possible, confirm the histologic class with biopsy,” he added.

He said biopsy is particularly useful when there is uncertainty about whether treatment should be intensified or, later, when clinicians are considering whether immunosuppression can be safely stopped.

The physician illustrated this latter scenario with a clinical case: a patient with lupus nephritis who had previously undergone a biopsy and presented with anti-dsDNA antibodies, rising serum creatinine, and proteinuria of 3.1 g in 24 hours. A new biopsy ruled out any inflammatory activity, which allowed for a reduction in immunosuppression, leading to clinical improvement and a lower risk for infections. In this case, the biopsy was the tool that made it possible to reduce the intensity of treatment. Klumb described three distinct timepoints at which the procedure is indicated: early biopsy, mid-term biopsy, and late biopsy, performed specifically to evaluate the discontinuation of immunosuppression.

There are situations, however, in which a biopsy cannot be performed. Very low platelet counts, active infection, end-stage kidney disease, platelet dysfunction, and renal failure are contraindications. The situation is different in stable patients, for whom the risk for the procedure is low and the potential benefit is high. “We need to be very careful not to make the wrong recommendation, but the potential benefit is so great that we shouldn’t avoid performing the biopsy out of fear,” emphasized Klumb.

Reis Neto offered a complementary perspective: Kidney biopsies are not always available, whether through the Unified Health System or private health insurance, and expanding access is a daily challenge. Furthermore, the time to treatment initiation has a direct impact on prognosis. “Studies show that the longer it takes to begin initial or induction treatment, the worse the patient’s prognosis,” he cautioned.

Biomarkers May Reshape Future Monitoring

Looking to the future, both physicians agree that new biomarkers could change the way lupus nephritis is monitored. Reis Neto cited among the most studied candidates urinary soluble CD163 and urinary interleukin-16, which are associated with the proliferative forms of the disease, as well as biomarkers linked to indices of histologic activity and response to treatment. Syndecan-1, which is still awaiting external validation, could be particularly useful in cases where a biopsy cannot be performed. Klumb also mentioned tenascin-C, a potential marker of chronicity, as well as galectin, but emphasized that neither is currently used to guide clinical decision-making.

The two physicians believe that these markers could be used for sequential monitoring between biopsies, complementing already established indicators such as anti-dsDNA antibody levels, serum complement, and active urinary sediment. “Liquid biopsy can be very useful, and I believe that within the next 5 years, we’ll be using it in our daily practice,” predicted Klumb.

Reis Neto was more cautious in his closing remarks: “At this time, however, renal biopsy remains the gold standard. The combination of these biomarkers will provide information and help us assess patients from both a broad and a detailed perspective in the future.”

This story was translated from Medscape’s Portuguese edition.