A silent immune attack on the kidneys afflicts many people. New treatments could make early diagnosis lifesavingNEWS | 17 March 2026This article is part of “Innovations In: Kidney Disease,” an editorially independent special report that was produced with financial support from Vertex.
The man in his 50s arrived at Ellie Kelepouris’s office carrying a sheaf of medical records. They contained years’ worth of laboratory test results that showed microscopic traces of blood in his urine. Kelepouris, a nephrologist at the University of Pennsylvania’s Perelman School of Medicine, wasn’t the first kidney specialist he had consulted about the problem. “I don’t want to have blood in my urine,” the man said. “I don’t know what’s going on.” Kelepouris suspected the cause, but it took a kidney biopsy, done in 2024, to confirm it. Her patient had IgA nephropathy (IgAN), an autoimmune disease that is an important cause of kidney failure.
IgAN is far from the most common cause of kidney disease, but up to 40 percent of people who have it will eventually require dialysis or a kidney transplant. Kelepouris’s patient was diagnosed while he was still in the early stages of the illness, but that’s uncommon. IgAN can develop asymptomatically for years, and by the time it’s detected, most patients are already at advanced stages. Today there are emerging precision therapies that can preserve kidney function and potentially stop IgAN in its tracks. But early diagnosis is crucial. The sooner treatment gets underway, the better the odds that “we can push off the need for dialysis, hopefully permanently,” says Brad Rovin, a nephrologist at the Ohio State University Wexner Medical Center.
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Usually an antibody protein known as immunoglobulin A, or IgA, patrols the inner walls of the body’s organs, blocking pathogens from entering cells. But in people who have IgAN, IgA is misshapen and not recognized by the rest of the immune system, prompting an attack against the perceived invader. When defective IgAs and their attackers bind, they aggregate into clumps that trigger inflammation in capillary networks in the kidneys called glomeruli. Inflamed blood vessels become scarred and unable to filter properly. The damaged kidneys leak proteins and red blood cells into the urine and allow too much salt and water to be retained in the body, raising blood pressure and putting undue stress on the remaining glomeruli.
For many, the first sign of the disease is urine turned bright red with blood. That typically happens after a cold or other virus. The virus increases immune activity, which ramps up IgA production and leads to an influx of new antibody clumps in the kidney. This inflammation damages the glomerular barrier, letting blood leak into the urine and “scaring the heck out of everybody,” Rovin says.
Ideally, nephrologists would identify patients before the disease becomes this advanced. But that has been difficult. A simple urine test can hint at early warning signs, but it takes a kidney biopsy to prove conclusively that someone has IgAN rather than some other condition. For a biopsy, doctors must push a needle from the patient’s back into one of their kidneys and pull out “two or three teeny pieces of tissue about the length of long grains of rice,” says Melanie Hoenig, a nephrologist at Beth Israel Deaconess Medical Center in Boston. Then a pathologist looks for IgA deposits in these specimens.
When patients have few to no symptoms, a kidney biopsy seems like an expensive and unreasonable ask. So it’s not done as often as nephrologists might like. In developing countries, the procedure is often not an option because of limited resources. But even in wealthier nations, doctors have hesitated to biopsy people with suspected cases of IgAN because—until the past few years—a confirmed diagnosis wouldn’t change their treatment.
Until recently, doctors could offer only harsh immunosuppressing drugs or basic supportive care to people in late stages of the disease. Instead of getting a biopsy, patients would be treated as having “chronic kidney disease of unknown etiology,” says Krzysztof Kiryluk, a nephrologist and physician scientist at Columbia University. “They would progress to end-stage renal disease without a proper diagnosis.”
Without biopsy-confirmed data, it’s difficult to pin down how common IgAN really is. Published estimates range from rates as low as 0.06 case per 100,000 people in South Africa to 4.2 cases per 100,000 people in Japan. Kiryluk suspects genetic factors drive differences in risk across racial and ethnic groups, noting that even in the U.S. “end-stage renal disease caused by IgAN is much more frequent among individuals of East Asian descent and rare among African Americans.” Current survey data, however, almost certainly underestimate IgAN’s true reach, he says, because they miss people who have the disease but weren’t biopsied.
Kelepouris believes that for every person with a biopsy-confirmed diagnosis, many more have the disease and don’t know it. And a significant fraction of these patients, she says, may be headed for kidney failure. She and other nephrologists argue that physicians should routinely screen their patients for IgAN, and it doesn’t take a biopsy to do so. One basic screening tool, a urine dipstick test, can detect traces of blood and protein and is very inexpensive. In Asian countries, primary care doctors use dipsticks regularly to look for signs of kidney disease during physical examinations, and Kelepouris’s patient was lucky that his U.S. doctors had done the same.
Some expert groups in the U.S. argue against urinary screening in asymptomatic people, however. They claim it isn’t cost-effective. The U.S. Preventive Services Task Force, an influential panel of primary care experts, has stated that screening lacks proven benefits and could actually cause harm because ambiguous results will lead to unneeded further tests and treatment in healthy people. A growing number of nephrologists, however, don’t buy into the excessive-harm argument. Dipsticks detect the presence of blood and protein with high accuracy, Rovin says. Jonathan Barratt agrees. Barratt, a nephrologist and professor at the University of Leicester in England, is widely considered one of the world’s leading IgAN experts and says arguments against urinary screening are out-of-date, particularly in light of newly approved IgAN treatments. The USPSTF’s latest kidney-screening guidelines were issued in 2012; according to its website, an update is now in progress.
Improvements in the therapeutic landscape compel a rethinking of screening for kidney diseases, especially in young adults.
Dipsticks, however, are a starting point, not a solution. They provide only semiquantitative information about protein or blood in a urine sample. If a dipstick test is positive, further lab tests to measure daily protein accumulations in urine can assess possible kidney damage and guide the next steps in the diagnosis.
One of those next steps, a potentially lifesaving one, could be a biopsy. For years medical guidelines advised doing the invasive procedure only if daily protein levels in the urine reached one gram or more. But in 2023 a large study in the U.K. showed that much lower protein levels were linked to poor outcomes. The research participants included nearly 2,500 biopsy-proven IgAN patients. Overall, the results showed that roughly a third of those with only moderate protein levels, ranging between 0.5 and 1.0 gram, died or developed kidney failure within 10 years. The finding marked an important turning point: doctors had previously thought such levels reflected mild or even benign conditions.
The standard was revised in 2025. The updated guidelines recommend a kidney biopsy for patients who leak half a gram of protein or more into their urine per day—a value that some nephrologists say is still too high. Kelepouris says she aims to keep urine protein levels in her patients below 300 milligrams. The man who brought his records to her office had test results showing 400 milligrams. When she asked for a biopsy, the pathologist pushed back. But Kelepouris’s insistence helped her patient get the biopsy that showed he was in early stages of the disease.
Thanks to newly developed medications, recently approved for kidney disease by the U.S. Food and Drug Administration, it also helped him get effective treatment. Previously, patients with suspected or confirmed IgAN had few good options. Doctors advised lifestyle changes, such as low-salt diets and exercise, in addition to supportive care with blood pressure medications and, more recently, GLP-1 receptor agonists such as Ozempic (which improve blood sugar control and ease kidney stress) and SGLT2 inhibitors (which help flush out sugar and salt) [see “Kidneys Get the Diabetes Treatment.”]
If urine protein excretion was consistently greater than one gram in a biopsy-proven patient, doctors might add a six-month course of high-dose prednisone, a steroid drug whose extended use can “have terrible side effects,” Kiryluk says. Over months it can cause weight gain, changes in appetite, sleep disturbances and bone loss, and it elevates the risk of infections. (Short-term use, of about a week, is safe.) “Patients really hate it, so compliance is low,” Kiryluk says.
Many drug companies weren’t motivated to come up with alternatives because of the lengthy timelines required to prove a benefit. To pass muster with the FDA, they would need to show that a drug protected against end-stage kidney failure, and “most companies are not going to invest in a trial that might be 10 or 20 years long,” Rovin says. “It doesn’t make sense financially.”
Frustrated by the lack of therapeutic options, the American Society of Nephrology teamed up with the FDA to create the Kidney Health Initiative, a cooperative forum for developing innovative treatments. The public-private partnership proposed a new pathway for accelerated approval of IgAN drugs. Instead of waiting for kidney failure to happen, companies had to show that a drug lowers protein levels in urine by 30 percent within the first nine months of treatment and that kidney-function decline slows for at least two years.
This change sparked a renaissance in IgAN drug development. Over the past five years there has been an explosion of late-stage clinical trials and approved therapies for people with the disease. “It has been like a continuous Christmas party,” Rovin says. The approved drugs target the immunological machinery that inflames and scars the glomeruli.
One such medication, budesonide (marketed as Tarpeyo), won accelerated approval in 2021 and was granted full approval two years later. Although budesonide is a steroid, it doesn’t affect the entire body like prednisone does. Instead it gets released only where IgA-producing B cells show up in the gut. Because it suppresses the immune cells that make faulty IgA, budesonide limits the deposition of antibody clumps in the glomeruli, thereby stanching the localized inflammation that gives rise to IgAN. “The drug allows other parts of the immune system to function normally,” Rovin says. “That’s a key innovation that keeps patients healthier.”
Another targeted therapy, sibeprenlimab (Voyxact), was approved by the FDA for IgAN in November 2025. It blocks faulty IgA in a different way, Rovin says. Sibeprenlimab inhibits an immune protein called APRIL (for “a proliferation-inducing ligand”). Ordinarily, APRIL coordinates with B cells to ensure that IgA antibodies are properly balanced for everyday defenses. But when IgAN patients face a routine infection, the protein starts pushing B cells to crank out the antibodies, which, because they’re abnormal in people with the illness, go on to form toxic clumps. Sibeprenlimab blocks that process—it inhibits APRIL, slashing IgA production so that fewer clumps lodge in the kidneys. During their respective clinical trials, targeted budesonide and sibeprenlimab both decreased urine protein levels by 31 to 60 percent.
How well these changes keep kidney failure and dialysis at bay must still be determined; companies are following treated patients over time. But Barratt says that improvements in the therapeutic landscape already compel a rethinking of screening for kidney diseases, especially in young adults. For many people in their 30s and 40s, early detection and the new medications could keep their kidneys healthy enough to stave off dialysis and kidney transplants. “We need to get these new drugs to patients as quickly as possible so we can protect kidney functioning,” he says.
Kelepouris agrees. After her patient went on targeted budesonide, his urinary protein level dropped to 50 milligrams, a “tremendous response,” Kelepouris says. “Now we have an opportunity to modify progression of the disease. Our goal is to shut dialysis units down.”Author: Lauren Gravitz. Charles Schmidt. Source
