Kidney health is a particularly big issue for people with systemic lupus erythematosus.Credit: Sebastian Kaulitzki/SCIENCE PHOTO LIBRARY/Getty Images
Lupus puts the body at war with itself. In patients with the most common form, systemic lupus erythematosus (SLE), the immune system mistakes healthy cells for foreign invaders and unleashes autoantibodies to attack them. The effects of this onslaught can be widespread, debilitating and even life-threatening1 for the estimated 5 million people worldwide who are living with SLE.2
Because SLE can cause diverse symptoms, which may vary over time, it is one of the most difficult autoimmune disorders to diagnose and treat.1 Compounding SLE’s complexities, disease activity often waxes and wanes unpredictably. Flare-ups, and associated systemic inflammation, can lead to irreversible organ damage: a complication that affects up to 50% of patients within five years of their SLE diagnosis.1
More than 1.5 million people develop one of the most dangerous manifestations of SLE: lupus nephritis (LN), characterized by immune system induced inflammation of the kidneys. Within 10 years, up to 20% of LN patients progress to end-stage renal disease, a potentially fatal condition that requires dialysis or a kidney transplant.3 Treatment options for LN have recently expanded, and several medical organizations around the world have published updated guidelines with new protocols to help physicians make the most strategic use of these therapies.
“Early and effective treatment, and the prevention of flares, represent the most important targets for SLE patients with kidney involvement,” says Marta Mosca, a rheumatologist at the University of Pisa in Italy. To improve long-term outcomes, Mosca adds that it’s also essential for physicians to be aware of the latest discoveries about how and why SLE progresses to LN, and which patients are most vulnerable.
A ‘treat to target’ approach — one that aims to not only manage symptoms, but also change the way an illness progresses — has been highly effective in changing outcomes in diseases such as rheumatoid arthritis, but hasn’t been consistently employed in lupus. Reasons include the need for consensus in the medical community on definitions of remission and low-disease activity, and the best methods to reach those endpoints, as well as a lack of crucial tools, such as biomarkers to track disease activity and disease-modifying therapies. But there is progress.
New global findings for at-risk populations
SLE accounts for 70% of lupus cases.3 Up to 10 times more common in women than men, SLE primarily affects young women ages 15 to 44. In recent years, more detailed estimates of SLE’s incidence have provided new insights into the disease burden, and who is at the greatest risk of its more severe complications.4
An important area of research has focused on the identification of biomarkers to predict which patients will benefit most from early intervention. A 30-year study of SLE patients found that up to one-third eventually developed abnormal levels of creatinine in their blood, indicating poor kidney function.5 Urinalysis may reveal abnormal levels of protein, another warning sign of LN. However, kidney biopsy remains the gold standard for diagnosis.
Although rates of LN vary widely across countries, studies consistently report that its prevalence is highest in patients of colour — including Caribbean, Native American, Black, Asian and Latinx/Hispanic patients — and may also be more severe in these populations. Conversely, in Europeans, LN tends to take a less aggressive course, leading some researchers to speculate that it may actually be a different disease, perhaps due to genetic factors.6
Research also suggests that almost all SLE patients develop some degree of kidney involvement, during the disease course.7 Chronic use of corticosteroids, particularly at higher daily doses, can raise patients’ risk of irreversible organ damage, says Liz Lightstone, a professor of renal medicine at Imperial College London, and an expert in LN. “In short bursts, steroids can be lifesaving, but the long-term effects are horrible: patients can end up with a round ‘moon face’, their bones can thin, and they can become diabetic or hypertensive. Long term, steroids can damage the patient more than the lupus.”
Mosca was part of an international team that updated European guidelines, issued by European Alliance of Associations for Rheumatology (EULAR) in 2019, and which advocated minimizing the use of steroids.8 EULAR also advises clinicians to consider biologic agents for patients with ongoing disease activity or frequent flares. “Combining drugs with different targets and complementary efficacy should become part of clinical routine, not only with traditional drugs, but also newer therapies,” she says.
Often underdiagnosed and misunderstood
Although treatment may improve long-term outcomes, it is often started too late. Part of the problem, at least in the United States, is that more than half (51%) of patients say they were diagnosed with lupus before or at the same time as LN, according to two surveys — one of patients and one of physicians — conducted in 2020 by the National Kidney Foundation (NKF) and the Lupus Research Alliance (LRA)9. What’s more, even when lupus is diagnosed, patients are rarely checked frequently for kidney disease.
The two surveys also uncovered disconnects between physicians, says Diane Gross, the LRA’s director of public health information. “One that I found astonishing — and a bit alarming — is that more than half the time, providers say that difficulty communicating with the rest of the patient’s medical team is a major barrier to delivering optimal care. This problem is also one of the major frustrations patients have with their clinicians.”
Gaps in doctor–patient communication were another common barrier, adds Gross. “After a lupus nephritis diagnosis, patients leave the office with their head spinning, trying to make sense of their disease and what it means. Our data show that 71% of patients rate ‘inadequate education about their condition’ as the top barrier they face in managing their health, while clinicians only consider this a problem 31% of the time.” Although minorities are disproportionately affected by SLE and LN, they’re told even less about their condition, the survey reported.
The findings highlight an urgent need for closer monitoring of patients and improved communication. For example, patients may not understand that one goal of the treat-to-target approach is to help them avoid long-term organ damage.
Transcending medical silos
Physicians also disagreed about who should take the lead in LN management: nephrology or rheumatology. Half of rheumatologists surveyed said LN is mainly managed by them, but only one in 10 nephrologists concurred.
However, a sizeable portion of respondents advocated a collaborative team approach for major clinical decisions — a model of care that’s rapidly gaining traction in Europe, says Lightstone. “SLE is a multi-organ disease that requires a multidisciplinary approach, with everybody working together.”
In Asia, consensus recommendations, published this year by an expert committee, strongly advocate that SLE be treated by a multidisciplinary team with an emphasis on shared decision-making between physicians and patients. Enhanced communication helps allay patients’ concerns about treatment toxicities and improves their compliance with the therapeutic plan, helping physicians achieve its central goals: to reduce organ damage and improve long-term survival.10
When it comes to a disease as complex and unpredictable as SLE, closer connections between providers can be lifesaving. One of the LN patients in the LRA/NKF survey commented: “I had trouble with all of my doctors communicating between each other, which led to me almost losing my life 16 years ago. Now, I have excellent care.”