Glomerulonephritis: How Your Immune System Attacks Kidney Filters

Imagine your kidneys are like tiny coffee filters, cleaning your blood 24/7. Now imagine your immune system, the body’s defense team, suddenly turns on those filters and starts attacking them. That’s glomerulonephritis - a condition where your own immune system damages the microscopic filtering units in your kidneys, called glomeruli. It’s not just a rare disease. It affects about 12.5 out of every 100,000 people in the U.S. every year, and it’s one of the top causes of kidney failure in younger adults.

What Happens Inside Your Kidneys When GN Strikes

Your kidneys don’t just remove waste. They also balance fluids, control blood pressure, and keep essential proteins in your blood. Each kidney has about a million glomeruli - tiny clusters of capillaries wrapped in a protective mesh of cells. These are the filters. They’re made of three layers: the endothelial cells lining the blood vessels, the basement membrane (a structural scaffold), and the podocytes - specialized cells that act like tiny feet gripping the filter.

In glomerulonephritis, the immune system sends antibodies or immune complexes to attack one or more of these layers. Sometimes it’s the basement membrane. Other times, it’s the podocytes. When podocytes get damaged, they can’t hold onto proteins anymore. That’s why you start losing large amounts of protein in your urine - a sign of nephrotic syndrome. Other times, red blood cells leak through the damaged filter, causing blood in the urine - a hallmark of nephritic syndrome.

The damage isn’t always obvious at first. Many people don’t feel sick until their kidneys are already struggling. Fatigue is the most common complaint, reported by 65% of patients. Swelling in the legs, ankles, or face from fluid retention is another early warning sign. High blood pressure often follows as the kidneys lose their ability to regulate fluid and salt.

The Two Main Types: C3 Glomerulonephritis and Immune Complex-Mediated MPGN

Not all glomerulonephritis is the same. Two major types dominate the clinical picture: C3 glomerulonephritis (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN).

C3G is driven by a broken complement system - a part of the immune system that normally helps clear infections. In C3G, the complement system goes haywire. It starts activating nonstop, flooding the glomeruli with C3 protein. Biopsies show C3 deposits 3 to 5 times higher than normal. About 60-70% of C3G cases involve autoantibodies called C3 nephritic factor, which tricks the immune system into thinking it’s under attack.

IC-MPGN, on the other hand, is caused by immune complexes - clumps of antibodies and antigens - getting stuck in the glomeruli. These are often leftovers from past infections like hepatitis or malaria, or they can form in autoimmune diseases like lupus. In 95% of IC-MPGN cases, electron microscopy reveals dense deposits in the filter walls.

The difference matters because treatment isn’t one-size-fits-all. C3G responds poorly to standard steroids. IC-MPGN might improve with immunosuppressants - but only if caught early.

Common Forms of GN You Should Know

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. It happens when IgA antibodies - normally used to fight gut infections - build up in the kidneys. In North America, it affects about 2.5 people per 100,000 each year. About 20-40% of those with IgA nephropathy will develop kidney failure over 20 years. It often shows up after a cold or sore throat, with bloody urine appearing within hours.

Post-streptococcal glomerulonephritis is more common in kids. After a strep throat or skin infection, the immune system can misfire and attack the kidneys. The good news? 95% of children recover fully within 6 to 8 weeks. Adults aren’t as lucky - their recovery rates are lower.

Lupus nephritis affects half to two-thirds of people with systemic lupus erythematosus. It’s not just a kidney problem - it’s a sign the whole immune system is out of control. With modern treatment, 70-80% of patients avoid kidney failure within 10 years. But without treatment, the risk of dialysis skyrockets.

Why Diagnosis Takes Time - and a Biopsy

There’s no blood test that can tell you exactly what type of glomerulonephritis you have. That’s why a kidney biopsy is the gold standard. A needle is inserted through the back to take a tiny sample of kidney tissue. It’s not risk-free - about 3-5% of patients have bleeding or severe pain afterward. But it’s the only way to see the pattern of damage under the microscope.

Interpreting that biopsy? That’s where things get hard. Nephropathologists need 5 to 7 years of specialized training to tell the difference between C3G, IC-MPGN, IgA nephropathy, and other subtypes. Many patients see three or more doctors before getting a clear diagnosis. On average, it takes 4.2 months from when symptoms start to when a biopsy confirms GN.

Patients on forums like Inspire.com and Reddit often say the delay is the hardest part. “I thought it was just dehydration,” one wrote. “By the time they told me it was my kidneys, I was already swollen and couldn’t walk up the stairs.”

Treatment: Steroids, Side Effects, and New Hope

For decades, corticosteroids like prednisone were the only weapon. They work - about 60-80% of patients see improvement in proteinuria or blood pressure. But the cost is high. Three out of four patients gain weight. One in three gets infections. Nearly one in four develops osteoporosis. One Reddit user shared: “Prednisone gave me two broken spine bones in 18 months. I was 32.”

New treatments are changing the game. For C3G, the drug iptacopan - approved by the FDA in early 2023 under breakthrough therapy status - cuts proteinuria by over 50% in 12 months. It targets a specific part of the complement system, leaving the rest of the immune system alone.

Another option, eculizumab, blocks a different complement protein. It works well in some patients - but costs about $500,000 a year. That’s why KDIGO guidelines recommend trying standard therapy for at least six months before jumping to these expensive drugs.

The future is personalization. Researchers are now using genetic and protein markers to predict who will respond to which treatment. One study showed that combining molecular data with biopsy results improved treatment prediction accuracy from 65% to 85%. Within five years, doctors may be choosing therapies based on your unique immune profile - not just what the biopsy looks like.

What Patients Are Really Living With

Beyond the lab results and drug names, glomerulonephritis changes daily life. Swelling makes clothes tight. Fatigue means skipping work or school. Medication side effects can be worse than the disease itself. On GN support forums, 78% of posts mention edema. 63% worry about steroid side effects. 51% live in fear of kidney failure.

But there are stories of hope. One patient on Reddit said: “Started rituximab within two months of diagnosis. Didn’t need dialysis.” Rituximab, a drug that clears out certain immune cells, is now being used off-label for severe IgA nephropathy and IC-MPGN with promising results.

The key? Early action. The sooner you catch it, the better your chances. If you’ve had blood in your urine after a cold, unexplained swelling, or persistent high blood pressure, ask your doctor about a urine test for protein and a blood test for creatinine. Don’t wait for symptoms to get worse.

The Bigger Picture: Who Gets GN and Why

Glomerulonephritis isn’t evenly distributed. IgA nephropathy is twice as common in East Asia as in North America. Lupus nephritis hits women more than men - especially those of African, Asian, or Hispanic descent. C3G is rare - only 1 to 2 people per million get it each year in Europe - but it’s more common in families with certain genetic mutations.

The global market for GN treatments is growing fast. It was worth $2.3 billion in 2022 and could hit $4.7 billion by 2028. That’s because autoimmune diseases are rising, and we’re getting better at diagnosing them. But here’s the dark side: in low-income countries, patients have 70% less access to biopsies and 90% less access to new drugs. A breakthrough therapy in the U.S. might be out of reach for someone in India or Nigeria.

Glomerulonephritis is more than a kidney disease. It’s an immune system gone wrong. It’s a biopsy that takes months to schedule. It’s a drug that costs more than a car. It’s fatigue that no one sees. But it’s also a field moving fast - from broad, toxic treatments to precise, targeted ones. And for those caught in the middle, the message is clear: don’t ignore the signs. Your kidneys are fighting a silent war. You can help them win.