Glomerulosclerosis is scarring of the glomeruli, the tiny filtering units inside your kidneys. Each kidney contains roughly a million of these microscopic structures, and when they scar over, they lose their ability to filter waste from your blood while keeping essential proteins in. The scarring can affect a few glomeruli or many, and it can develop as a primary kidney disease or as a consequence of other conditions like diabetes and high blood pressure.
How the Scarring Develops
Your glomeruli are bundles of tiny capillaries wrapped in specialized cells called podocytes. These podocytes act like a fence around the capillaries, maintaining the filtration barrier that lets waste and water pass through while blocking proteins and blood cells. When podocytes are injured, they can’t regenerate. The remaining podocytes stretch and enlarge to cover the gaps, but this compensation has limits.
As damaged podocytes fail, the filtration barrier breaks down and proteins start leaking into the urine. The capillaries inside the affected glomerulus begin to collapse and shrink. Other cell types in the area proliferate in response to the injury, and the whole process eventually produces scar tissue that permanently replaces functional filtering tissue. Once a glomerulus scars over, it stops working entirely, placing more strain on the remaining healthy glomeruli and creating a cycle that can accelerate further damage.
Focal Segmental vs. Diffuse Patterns
The most commonly discussed form is focal segmental glomerulosclerosis (FSGS). “Focal” means only some glomeruli are affected, and “segmental” means only a portion of each affected glomerulus is scarred. Early in the disease, this patchy pattern is typical. As the disease progresses without treatment, scarring can become more diffuse and global, meaning it spreads to more glomeruli and eventually involves entire filtering units rather than just segments.
This distinction matters for diagnosis because a kidney biopsy taken early may only catch a few damaged glomeruli, making FSGS notoriously difficult to confirm. If the biopsy sample happens to miss the scarred areas, the disease can be underdiagnosed.
What Causes It
Glomerulosclerosis has both primary and secondary forms. In primary FSGS, the podocyte injury arises from the kidney itself, often through immune-related mechanisms that aren’t fully understood. Secondary glomerulosclerosis develops as a downstream effect of another condition that puts chronic stress on the kidneys.
The most common secondary causes are diabetes, high blood pressure, and obesity. All three conditions force the kidneys to filter more blood at higher pressures, gradually wearing down the glomeruli over years or decades. This is why glomerulosclerosis is frequently found in people with long-standing, poorly controlled hypertension or diabetes, even when they didn’t start out with a primary kidney problem.
Genetics also play a significant role. Variants in a gene called APOL1, found predominantly in people of African descent, substantially increase the risk of hypertension-related kidney damage. These variants originally evolved because they offered protection against a parasitic infection (trypanosomiasis), but they carry the tradeoff of heightened kidney vulnerability. More than 50 genetic variants across genes like UMOD, MYH9, and SHROOM3 have been linked to declining kidney function and susceptibility to glomerular injury.
Symptoms and Warning Signs
The hallmark of glomerulosclerosis is protein leaking into the urine, a condition called proteinuria. In mild cases, you may not notice anything at all. As more protein escapes, urine can become foamy or bubbly. When protein loss becomes severe (called nephrotic-range proteinuria), the drop in blood protein levels causes fluid to shift out of your blood vessels and into surrounding tissues, leading to visible swelling in the ankles, legs, feet, and sometimes around the eyes.
High blood pressure often accompanies or worsens glomerulosclerosis, and the two conditions feed each other. Rising blood pressure damages more glomeruli, and damaged glomeruli impair the kidney’s ability to regulate blood pressure. Weight gain from fluid retention and fatigue from declining kidney function are also common as the disease progresses.
How It’s Diagnosed
A kidney biopsy remains the only definitive way to confirm glomerulosclerosis. A small sample of kidney tissue is examined under a microscope for the characteristic signs: scarring, collapsed capillaries, and adhesions within the glomeruli. The challenge is that because the scarring is often focal, a biopsy may not capture enough damaged glomeruli to make a clear diagnosis. Researchers have identified blood and tissue markers, including elevated levels of a soluble immune receptor called suPAR, that may help support the diagnosis, but none have replaced the biopsy as the gold standard.
Before a biopsy is considered, routine lab work typically reveals the problem. A urine test showing high protein levels, combined with blood tests showing low albumin and impaired kidney filtration, raises strong suspicion. These findings prompt the biopsy to determine the specific type of kidney disease.
Treatment Approaches
The foundation of treatment for all forms of glomerulosclerosis is controlling blood pressure and reducing protein loss. Medications that block the effects of a hormone called angiotensin (ACE inhibitors and ARBs) are the mainstay. These drugs relax blood vessels in the kidney, lower the pressure inside the glomeruli, and significantly reduce the amount of protein leaking into the urine. For secondary forms of glomerulosclerosis caused by conditions like obesity or high blood pressure, these medications combined with good blood pressure control are often sufficient.
Primary FSGS with severe protein loss typically requires a more aggressive approach. Steroid therapy and other immune-suppressing medications are used to try to halt the immune-mediated podocyte damage. These treatments work best when kidney function is still reasonably preserved, so early diagnosis matters.
Diet and Lifestyle Changes
Dietary adjustments are a meaningful part of slowing disease progression. The two biggest levers are sodium and protein intake.
- Sodium: Kidney guidelines recommend keeping sodium below 2 grams per day (about 5 grams of table salt) for people with kidney disease and high blood pressure. The American Heart Association sets an even lower target of 1.5 grams for high-risk patients. Lowering sodium helps control blood pressure and works together with medications to reduce protein in the urine.
- Protein: While protein is essential, excess dietary protein increases the workload on damaged kidneys. In early kidney disease, a standard intake of 0.8 grams per kilogram of body weight per day is recommended. As kidney function declines, that target drops to 0.55 to 0.6 grams per kilogram. For someone weighing 70 kg (about 154 pounds), that’s roughly 39 to 42 grams of protein daily, well below what most Western diets provide. Adequate calorie intake of 30 to 35 calories per kilogram is important alongside protein restriction to prevent muscle wasting.
Long-Term Outlook
Glomerulosclerosis is a progressive condition, but the speed of progression varies widely depending on the underlying cause, how early it’s caught, and how well it responds to treatment. In a large study of various glomerular diseases, about 21% of patients eventually progressed to end-stage kidney disease requiring dialysis or transplant, while roughly 8% died from related complications before reaching that point. The remaining majority maintained some level of kidney function with ongoing management.
People who achieve a significant reduction in proteinuria with treatment tend to have the best outcomes. Those whose protein loss remains high despite therapy face a steeper decline. The combination of blood pressure control, protein reduction, dietary changes, and addressing underlying conditions like diabetes gives the best chance of preserving kidney function for as long as possible.