CHICAGO — The current recommended benchmark for when to biopsy the kidney in patients with systemic lupus erythematosus (SLE) is arbitrary and results in missing the lupus nephritis (LN) cases that a lower bar could have captured, authors of a new study said.

Current American College of Rheumatology, European Alliance of Associations for Rheumatology, and Kidney Disease: Improving Global Outcomes guidelines recommend a kidney biopsy in patients with SLE with a urine protein to creatinine ratio (UPCR) of at least 0.50 g/g. However, patients who undergo kidney biopsy at a lower UPCR are often found to have fast-growing LN, as demonstrated in previous research, including a study by Shudan Wang and colleagues.

The current threshold for biopsy “is way too much,” said Michelle Petri, MD, MPH, director of the Lupus Center at Johns Hopkins University School of Medicine in Baltimore, who presented the study in a plenary session at the American College of Rheumatology (ACR) 2025 Annual Meeting. “My job this morning is to convince you that all three of our lupus nephritis guidelines are wrong or outdated, and we need to change.”

A Look at LN With a Lower UPCR

In the current study, Petri and her team investigated the first onset of LN with a UPCR from 0.250 to 0.499 g/g. The research was done as part of the early disease project under the Accelerating Medicines Partnership (AMP) Lupus Network.

The study included 28 patients with treatment-naive SLE with no history of LN and a UPCR of 0.250-0.499 g/g plus another predictor of LN, including non-White race, serologies (low C3 or low C4 complement levels) or anti-double-stranded DNA (anti-dsDNA), or active urine sediment. Kidney biopsies were completed and reported as International Society of Nephrology class I-VI with National Institutes of Health Activity and Chronicity Indexes, if LN was present.

Of the 28, 25 (89%) were anti-dsDNA positive, 20 (71%) had low C3, and 19 (68%) had low C4 at enrollment. All had a normal glomerular filtration rate > 60 and were not receiving immunosuppression but were receiving prednisone (< 10 mg/d).

The researchers found that 20 patients had LN: two class I, five class II, six class III, and seven class V. Eight did not have LN. In longitudinal follow-up, two in class II, two in class III, and three in class V progressed to > 0.5 g/g of UPCR (despite treatment of class III and class V). Petri highlighted the progression of the patients with class II LN and said, “Class II maybe shouldn’t be considered such a benign lesion anymore.”

“Overall, 71% of the patients had lupus nephritis, and in about half, it was actionable,” Petri said.

“Lupus is the fifth or sixth leading cause of death for young women in the United States. Having lupus nephritis increases the risk of dying eightfold,” Petri said. “There are very disturbing national data showing an increase in deaths from lupus nephritis from 2015 to 2020, so pre-pandemic. This is a clear call to action. We need to do better.”

Lupus Specialists Were Already Doing Biopsies at a Lower UPCR

“I absolutely love” the abstract, lupologist Donald Thomas, MD, told Medscape Medical News. Thomas, who is a clinical professor of medicine at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, said he agrees that the current biopsy trigger level is too high and arbitrary. He’d like to see the guidelines change as well, noting that rheumatologists who aren’t lupus specialists are likely to stick closely to the guidelines.

Lupologists, however, have already been doing biopsies when a patient’s UPCR was abnormal but < 0.5 g/g and the patient had risk factors for LN, such as low C3 or C4 or high anti-dsDNA, Thomas said. Identifying patients with LN and treating them early is essential, he noted. History of low C3 or C4 was the most important component of the AMP algorithm.

“Some of the patients did have class I and class II, which we wouldn’t treat except for using hydroxychloroquine, but [Petri] did find a significant amount with class III and class V lupus nephritis. The problem is that the longer someone goes on with active lupus nephritis without going into complete remission, the greater the chance of end-stage kidney disease. It’s worth doing the biopsy to catch those patients and get them on treatment right away.” Additionally, “it’s a very safe outpatient procedure,” he said.

Thomas said lowering the biopsy level was a hot topic at the International SLE conference in Toronto in May 2025, and he sees momentum toward changing the guidelines.

This abstract will help, he said, as Petri “has stronger evidence for her recommendation than the [0.5 g/g] recommendation does.”

Petri reported having relationships with multiple pharmaceutical companies. Thomas reported having no relevant financial relationships.

Marcia Frellick is an independent, Chicago-based healthcare journalist and a regular contributor to Medscape Medical News.