Current Treatment Options for C3 Glomerulopathy (C3G) and IgA Nephropathy (IgAN)

Complement 3 glomerulopathy (C3G) and immunoglobulin A nephropathy (IgAN) are uncommon forms of chronic kidney disease (CKD) that affect the glomeruli—the tiny filtration units of the kidneys.

In both disorders, abnormal protein deposits accumulate within the glomeruli, triggering inflammation, scarring, and a gradual loss of filtering capacity.

If left untreated, the ongoing inflammation accelerates CKD progression and raises the risk of complications. Early, evidence‑based therapy can help preserve kidney function.

Although C3G and IgAN share a glomerular origin, the culprit proteins differ.

C3G results from excess complement component 3 (C3) that builds up when the complement cascade—a key arm of innate immunity—becomes dysregulated.

The complement system normally defends against infection, but uncontrolled activation deposits C3 in the kidneys and drives injury.

IgAN is an immune‑mediated disease in which immunoglobulin A (IgA) antibodies accumulate in the glomeruli. In some patients, these IgA deposits also activate the complement pathway, creating secondary C3 deposits.

Because both conditions are glomerular, many therapeutic strategies overlap.

Blood‑pressure control: ACE inhibitors and angiotensin‑II receptor blockers (ARBs) lower systemic pressure, reduce glomerular hyperfiltration, and diminish proteinuria—the leakage of protein into urine.

Targeting inflammation can be approached in two ways:

• Suppressing the immune response that generates pathogenic deposits.
• Directly dampening the inflammatory cascade within the glomeruli.

Short courses of corticosteroids are sometimes combined with immunosuppressants, but long‑term steroid use is no longer routine. Enteric‑targeted budesonide (Nefecon) has emerged as a guideline‑endorsed option for IgAN.

Immunosuppressive agents—including mycophenolate, cyclophosphamide, and calcineurin inhibitors—are selected based on disease severity, biopsy findings, and individual tolerance. A 2022 systematic review reported mixed outcomes, indicating that benefits may be patient‑specific.

Complement‑inhibiting drugs are gaining traction, especially for C3G where the complement pathway is central. Eculizumab and ravulizumab block terminal complement activation, while iptacopan, a factor B inhibitor, received recent FDA approval for both C3G and IgAN.

Not every patient requires a complement inhibitor; the decision hinges on the presence of C3‑driven pathology.

Plasma exchange (plasmapheresis) removes circulating C3, IgA immune complexes, and auto‑antibodies. Evidence from a 2019 review suggests variable efficacy and underscores the need for more rigorous trials.

When kidney function declines substantially, dialysis provides mechanical clearance of waste and excess fluid but does not treat the underlying disease.

Kidney transplantation remains an option, yet recurrence rates are high. Approximately 50 % of transplanted kidneys for C3G fail, reflecting the immune‑mediated nature of the disease.

Dietary measures—such as modest sodium and protein restriction—are recommended by the National Kidney Foundation to lessen glomerular workload. Preliminary data also suggest that omega‑3 fatty acids (fish oil) may exert modest anti‑inflammatory effects in IgAN.

Newer oral agents are expanding the therapeutic armamentarium. Sparsentan (Filspari), approved by the FDA in 2023, reduces proteinuria by simultaneously blocking endothelin‑1 and angiotensin‑II receptors. Sodium‑glucose cotransporter‑2 (SGLT‑2) inhibitors, originally developed for diabetes, have shown promise in slowing CKD progression in IgAN; dapagliflozin, for example, lowered the risk of end‑stage kidney disease in a recent analysis.

More than 25 clinical trials for C3G are currently recruiting or underway (ClinicalTrials.gov). Patients interested in research participation can explore listings at clinicaltrials.gov.

There is currently no cure for C3G or IgAN. Both diseases are progressive, but timely, individualized therapy can delay the onset of end‑stage kidney disease. Long‑term data indicate that 20‑50 % of IgAN patients develop ESRD within 30 years of diagnosis, while up to half of C3G patients reach ESRD within a decade.

Because these disorders are rare and under‑studied, definitive prognostic predictions remain limited. Nonetheless, a combination of blood‑pressure agents, immunosuppressants, and, when appropriate, complement inhibitors forms the cornerstone of modern management.