What is IgA Nephropathy (IgAN)?

IgA nephropathy is considered rare overall, with a global incidence of roughly 2 to 3 people per 100,000 each year. In the United States, only a small fraction of people with kidney disease have it, and many do not know they have it until kidney function has already dropped. Without treatment, a significant number of people with IgA nephropathy eventually develop kidney failure over many years, but the timeline is different for everyone.

IgA nephropathy is the most common primary glomerular disease worldwide, even though its incidence in the general population is low. Rates are higher in parts of East Asia and lower in the United States. Many patients live for years with mild findings, while about 30 to 40 percent historically progressed to kidney failure within 20 to 30 years of diagnosis. Modern therapies have begun to shift these outcomes, especially for patients identified earlier and treated more aggressively.

Population studies show marked geographic variation in incidence, partly due to differences in biopsy and screening practices and genetic background. Cohort data from the pre targeted-therapy era suggest that roughly one-third of patients progressed to end-stage renal disease within 20 to 30 years, particularly those with persistent proteinuria, lower eGFR at diagnosis, or high-risk MEST-C features such as segmental sclerosis or tubulointerstitial fibrosis. Earlier diagnosis and disease-specific interventions appear to be altering this trajectory, but long-term outcome data in the modern treatment era are still emerging.

Doctors do not know the exact cause of IgA nephropathy. Most evidence suggests that it comes from a mix of genes, the immune system, and triggers such as infections of the nose, throat, or gut. In IgA nephropathy, the body makes an unusual form of the antibody IgA called galactose-deficient IgA1. The immune system then reacts to this aberrant form and creates autoantibodies that form immune complexes that deposit in the kidney filters. This is not caused by anything a person did wrong, and it is usually not linked to one specific infection, food, or lifestyle choice.

Current research views IgA nephropathy as an autoimmune disease of the mucosal immune system. People with IgA nephropathy tend to overproduce galactose deficient IgA1 in mucosal tissues such as the gut and upper airways, where immune cells are constantly exposed to infections and other triggers. Autoantibodies against this altered IgA1 help create circulating immune complexes that lodge in the glomerular mesangium, activate complement, and injure podocytes and nearby structures. Genetics increase the risk: many patients carry susceptibility variants that affect IgA regulation, mucosal immunity, or complement, but no single gene or trigger fully explains why one person develops IgA nephropathy and another does not.

The pathogenesis of IgA nephropathy is often described using a multi hit model. Hit 1 is increased production of galactose deficient IgA1 from mucosal immune sites, driven by abnormal regulation of B cells and plasma cells. Hit 2 is the development of glycan specific autoantibodies, usually IgG and or IgA, that recognize this galactose deficient IgA1. Hit 3 is the formation of circulating immune complexes that contain galactose deficient IgA1, autoantibodies, and complement components such as C3. Hit 4 is mesangial deposition of these complexes with complement activation, leading to mesangial hypercellularity, podocyte damage, segmental sclerosis, and tubulointerstitial fibrosis. Genome wide association studies have identified multiple susceptibility loci in pathways related to IgA production, mucosal immunity, and complement, but these variants mainly modify risk and do not identify a specific cause in individual patients. For most people with IgA nephropathy, the exact combination of genetic background and environmental exposures that triggered the disease remains unknown.

IgA nephropathy does not look the same in everyone. Some people feel completely well and only find out they have it when routine urine tests show blood (hematuria) or extra protein (proteinuria). Others notice cola-colored or pink urine during or after infections of the nose, throat, or gut. Some develop swelling in the legs or around the eyes, feel more tired, or are told they have reduced kidney function based on blood tests. Many people have no warning symptoms until lab results show that kidney function has already fallen.

The presentation of IgA nephropathy ranges from isolated microscopic hematuria with low-level proteinuria, to more persistent hematuria with moderate proteinuria, to cases with heavy proteinuria, lower eGFR, and clear evidence of CKD at diagnosis. Some patients present with episodes of gross hematuria linked to infections, while others are detected through screening or an evaluation for high blood pressure or abnormal kidney tests. A smaller group presents with acute kidney injury (AKI), often during severe flares with heavy hematuria, and biopsy may show crescents and more aggressive lesions. This wide range of clinical patterns reflects differences in how much immune complex deposition, complement activation, and scarring have already occurred by the time the disease is recognized.

For nephrologists, the heterogeneity of IgA nephropathy is captured by combining clinical data and biopsy findings. Some patients have stable eGFR, low-grade proteinuria measured by UPCR or UACR, and relatively mild MEST-C scores dominated by mesangial hypercellularity. Others present with higher-grade proteinuria, lower baseline eGFR, hypertension, and biopsies showing segmental sclerosis, crescents, and tubulointerstitial fibrosis. KDIGO risk stratification uses the level and persistence of proteinuria, eGFR, and MEST-C features to separate lower-risk courses from those at higher risk of progression to kidney failure. This spectrum of presentations explains why some people live for decades with slowly changing labs, while others need early, intensive therapy to prevent or delay advanced CKD.

As IgA nephropathy gets worse over time, the kidneys filter blood less well, so eGFR goes down and creatinine goes up. More protein leaks into the urine, so proteinuria and values like UPCR and UACR increase. These changes reflect growing stress on the kidney filters and nearby tissue.

Structural damage starts with mesangial hypercellularity that distorts the glomerular tuft, followed by segmental sclerosis that reduces the working filtration area. Crescents can form when severe injury extends into Bowman space. Tubulointerstitial fibrosis then develops around the tubules, further lowering kidney function and contributing to higher BUN and falling albumin and serum albumin in advanced cases.

When glomerulosclerosis and tubulointerstitial fibrosis become widespread, loss of functioning kidney units is largely irreversible and CKD progression accelerates. Over months to years this chronic damage drives a steady decline in eGFR and persistent proteinuria. KDIGO staging uses eGFR categories and proteinuria levels, often derived from UPCR and UACR together with MEST-C features, to estimate future risk of kidney failure and to shape the intensity of follow-up and therapy in IgA nephropathy.

IgA nephropathy is a chronic kidney disease (CKD), which means damage usually builds up slowly over many years. People with IgA nephropathy can also have sudden drops in kidney function called acute kidney injury (AKI), for example with infections, severe flares of blood in the urine, dehydration, or certain medicines. AKI can sometimes get much better when the trigger is treated or removed, while the CKD changes from IgA nephropathy tend to be longer lasting.

In IgA nephropathy, CKD reflects long-standing structural damage such as glomerulosclerosis and tubulointerstitial fibrosis that show up on kidney biopsy and are captured in the MEST-C score. Acute kidney injury (AKI) in IgA nephropathy, by contrast, often presents as a rapid rise in serum creatinine (SCr) and fall in eGFR over days to weeks, sometimes during episodes of heavy hematuria or another illness or stress on the body. With timely treatment, kidney function can often recover toward the prior baseline, even though the underlying CKD from IgA nephropathy remains.

For nephrologists, separating the reversible AKI component from the irreversible CKD burden in IgA nephropathy is critical for prognosis and treatment decisions. Short-term changes in SCr and eGFR over hours to days (and up to about a week) usually reflect AKI, whereas gradual declines over months to years correlate more with accumulated glomerulosclerosis and tubulointerstitial fibrosis. KDIGO guidance distinguishes AKI from CKD by the time course and persistence of dysfunction, and in IgA nephropathy an accurate assessment of AKI versus CKD helps interpret MEST-C findings, anticipate eGFR recovery, and decide how aggressively to treat and monitor.

Blood pressure and pressure inside the kidney filters are strongly controlled by the renin angiotensin aldosterone system (RAAS). RAAS blockade with ACE inhibitors or ARBs can lower this pressure and reduce proteinuria. SGLT2 inhibitors are medicines that help the kidneys handle sugar and salt and can further protect kidney function in IgA nephropathy.

ACE inhibitors (ACEi) such as lisinopril (Prinivil, Zestril) and ARBs such as losartan (Cozaar) lower intraglomerular pressure and are standard parts of RAAS blockade for IgA nephropathy. By reducing glomerular capillary pressure they slow development of glomerulosclerosis and help stabilize eGFR. SGLT2 inhibitorscomplementRAAS blockade by reducing tubular sodium reabsorption and the workload on the glomerulus, which in turn can improve UPCR and UACR.

SGLT2 inhibitors including dapagliflozin (Farxiga), empagliflozin (Jardiance), and canagliflozin (Invokana) have shown broad kidney protective effects across CKD, and their impact on proteinuria and eGFR slope makes them attractive add-ons in IgA nephropathy. Together, RAAS blockade and SGLT2 inhibitors address pressure-related and tubular contributors to CKD progression, consistent with KDIGO recommendations that prioritize control of proteinuria and preservation of eGFR in proteinuric glomerular disease.

Newer treatments for IgA nephropathy do more than control blood pressure. The 2025 KDIGO guidelines describe a two-part plan: one part uses medicines such as targeted-release formulation budesonide (TRF-budesonide, also referred to as Tarpeyo, Nefecon, and Kinpeygo) or sibeprenlimab (marketed as Voyxact) or, in some cases, steroids to reduce the harmful IgA antibodies and immune complexes that drive the disease. The other part uses medicines such as renin angiotensin system (RAS) blockers, sparsentan (Filspari), and SGLT2 inhibitors to lower stress in the kidney filters, reduce proteinuria, and manage the long-term effects of nephron loss. More recently, other drugs such as atrasentan (Vanrafia) and iptacopan (Fabhalta) have also been shown to reduce proteinuria in adults with IgA nephropathy.

You can view a thorough list of approved medications on this site's treatments page.

In the KDIGO 2025 framework, one treatment pillar aims to reduce pathogenic IgA and IgA immune complex formation. At present this mainly includes targeted-release formulation budesonide (TRF-budesonide, Tarpeyo) or sibeprenlimab (Voyxact) or, in selected high-risk patients, reduced-dose systemic corticosteroids. The second pillar targets the consequences of IgA nephropathy-induced nephron loss with optimized renin angiotensin system inhibitors (RASi, ACEi or ARB) or with the dual endothelin angiotensin receptor antagonist sparsentan (Filspari), together with an SGLT2 inhibitor when tolerated to further reduce proteinuria and slow chronic kidney disease (CKD) progression. Iptacopan (Fabhalta) is an oral factor B inhibitor that blocks the complement alternative pathway at the glomerular level; in clinical trials it has reduced proteinuria and slowed eGFR decline, and its IgA nephropathy indication currently has FDA accelerated approval based on reduction in UPCR. Atrasentan (Vanrafia), a highly selective endothelin type A receptor antagonist, also has FDA accelerated approval to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression, although it was not specifically included in the original KDIGO evidence base.

Upstream control of the IgA nephropathy process can be extended beyond TRF-budesonide and systemic corticosteroids to therapies that reshape B cell signaling and plasma cell activity. APRIL and BAFF, also called BLyS or B cell activating factor, promote survival and maturation of antibody-producing cells. Agents such as sibeprenlimab (Voyxact) and zigakibart (BION-1301) target APRIL, while atacicept, telitacicept (Tai'ai, RC18), and povetacicept (ALPN-303) variously modulate BAFF, APRIL, or the shared receptor TACI to lower Gd-IgA1 production and reduce proteinuria measured by UPCR and UACR. Complement-targeting therapy with iptacopan (Fabhalta) addresses another upstream amplifier by inhibiting factor B in the complement alternative pathway, while sefaxersen (RO7434656, IONIS-FB-LRx) is an investigational antisense oligonucleotide designed to lower factor B production and suppress the alternative complement pathway. In parallel, the downstream pillar of RASi, sparsentan as a DEARA option, endothelin receptor antagonists such as atrasentan (Vanrafia), and SGLT2 inhibitors addresses hemodynamic and tubular consequences of nephron loss. The overall KDIGO 2025 strategy combines upstream disease-specific control with downstream CKD management, while newer agents like iptacopan and atrasentan extend the range of options for reducing proteinuria and stabilizing eGFR in IgA nephropathy.

Plasma cells are a type of immune cell that makes antibodies, including the Gd-IgA1 antibodies involved in IgA nephropathy. Plasma cell-directed therapies, currently in clinical trials, try to lower these harmful antibodies at their source so that less IgA builds up in the kidneys. This may help reduce proteinuria and slow loss of kidney function.

Many plasma cell-directed therapies in IgA nephropathy focus on CD38, a marker found on plasma cells. CD38-targeting agents such as mezagitamab (TAK-079) and felzartamab (MOR202) can reduce CD38-positive plasma cell numbers and lower Gd-IgA1 production. As upstream antibody drivers quiet, glomerular injury, mesangial hypercellularity, and segmental sclerosis may stabilize, and proteinuria can improve.

For nephrologists, CD38-directed therapies represent a strategy that is mechanistically distinct from RAAS blockade, SGLT2 inhibition, and APRIL-BAFF-TACI modulation. By selectively depleting or modulating plasma cells, these agents aim to lessen harmful Gd-IgA1 antibody levels and allow podocytes and tubulointerstitial compartments to recover to the extent possible. Their integration with other disease-specific agents and KDIGO-based CKD care will depend on long-term data on eGFR slope, MEST-C evolution, infection risk, and durability of plasma cell suppression.

TRAP degraders are a newer type of medicine that remove harmful proteins such as Gd-IgA1 from the blood. Instead of changing how antibodies are made, they help the body clear these proteins more quickly, which may ease stress on the kidneys and, if sustained, could reduce proteinuria.

TRAP (Targeted Removal of Aberrant Protein) degraders bind to specific circulating proteins and guide them to liver cells for breakdown. BHV-1400 is a TRAP degrader designed to recognize Gd-IgA1 in IgA nephropathy, while BHV-1600 is a TRAP degrader for β1-adrenergic receptor autoantibodies and BHV-1300 is an IgG MoDE degrader, together illustrating how related extracellular degrader platforms can be applied to different antibody targets. In principle, this approach can lower the load of disease-causing antibodies or antibody complexes without directly altering plasma cells or B cell signaling.

For clinicians, TRAP degraders offer an extracellular complement to RAAS blockade, SGLT2 inhibitors, DEARA therapy, complement alternative pathway inhibition, APRIL-BAFF-TACI modulation, and CD38-directed plasma cell therapies. By selectively clearing Gd-IgA1 and related targets from the circulation, agents such as BHV-1400 have the potential to reduce IgA deposition, improve UPCR and UACR, and favorably influence MEST-C progression and CKD outcomes while leaving the broader antibody repertoire and immune system more intact than broad immunosuppression.