Diabetes is the single most common cause of kidney failure. High blood sugar, sustained over years, gradually destroys the tiny filtering units inside the kidneys until they can no longer clean the blood effectively. High blood pressure is the second leading cause, and together these two conditions account for the majority of kidney failure cases worldwide.
But kidney failure isn’t always a slow process. Severe infections, certain medications, autoimmune diseases, and inherited conditions can all damage the kidneys, sometimes rapidly. Understanding what drives kidney failure helps explain why it happens and what makes some people more vulnerable than others.
How Diabetes Damages the Kidneys
Each kidney contains roughly one million tiny filtering units called nephrons. Blood flows through a cluster of microscopic blood vessels inside each nephron, where waste products and excess fluid are filtered out while useful proteins and blood cells stay behind. In people with diabetes, persistently high blood sugar triggers a chain of damaging changes in these filters.
Excess glucose causes the filtering clusters to enlarge and produce too much of a growth signal that drives scarring. Collagen and other structural proteins build up in the filter walls, thickening them and making them stiff. Over time, this scarring narrows the tiny blood vessels, reduces blood flow, and forces the remaining healthy filters to work harder. The overworked filters begin leaking protein into the urine, one of the earliest detectable signs of kidney damage from diabetes. This condition, called diabetic nephropathy, typically develops over 10 to 20 years of poorly controlled blood sugar, though the timeline varies. Without intervention, the kidneys lose filtering capacity until they can no longer sustain life without dialysis or a transplant.
High Blood Pressure and Kidney Damage
Healthy kidneys have a built-in pressure regulation system. The small arteries leading into each filtering unit can tighten or relax to keep internal pressure steady, even when blood pressure in the rest of the body fluctuates. This protective mechanism works well within a normal range, but chronic high blood pressure eventually overwhelms it.
When blood pressure stays elevated for years, the walls of these small arteries slowly thicken and harden, a process called nephrosclerosis. Blood flow to the filters decreases, and the kidneys gradually lose function. This form of damage develops slowly, often without obvious symptoms or significant protein in the urine, which is why many people don’t realize their kidneys are suffering.
In more extreme cases, very high blood pressure can cause acute, destructive injury. The small vessels develop tears, clots, and areas of dead tissue. If someone also has a condition that impairs the kidneys’ ability to regulate their own internal pressure (diabetes being one common example), the threshold for damage drops significantly. This is why diabetes and high blood pressure together are far more dangerous to the kidneys than either condition alone.
Autoimmune and Inflammatory Causes
The immune system can attack the kidneys directly. Glomerulonephritis, a group of conditions that inflame the kidney’s filtering units, is a significant cause of kidney failure worldwide. Infections and immune system disorders are among the most common triggers. When filters become inflamed, they leak blood and protein into the urine and gradually lose their ability to function.
Lupus is one of the better-known autoimmune causes. The disease can target the kidneys early, often around the same time a person first develops joint pain, muscle aches, unexplained fevers, or the characteristic butterfly-shaped facial rash. Between 10 and 30 percent of people with lupus-related kidney inflammation eventually develop kidney failure, according to the National Institute of Diabetes and Digestive and Kidney Diseases. Early signs include foamy urine, swelling in the legs, feet, or ankles, and rising blood pressure. Catching kidney involvement early and treating the underlying immune attack can slow or prevent progression.
Polycystic Kidney Disease
Some people are born with a genetic mutation that causes fluid-filled cysts to grow throughout both kidneys. In autosomal dominant polycystic kidney disease, the most common inherited form, a single copy of the faulty gene from one parent is enough to cause the condition. Cysts enlarge over decades, compressing and replacing normal kidney tissue.
The average untreated person with this condition reaches kidney failure around age 60, though people with rapidly progressing disease can get there much earlier. Because the cysts grow slowly, many people don’t know they have the condition until imaging for another reason reveals enlarged, cyst-filled kidneys. Pain, high blood pressure, and urinary tract infections are common complications along the way.
Acute Kidney Failure From Infections
Not all kidney failure develops gradually. Acute kidney injury can strike within hours or days, and the most common culprit is sepsis, a life-threatening response to infection. Between one-third and one-half of all acute kidney injury cases are believed to be caused by sepsis.
During sepsis, the body’s response to infection spirals out of control. Blood pressure drops, clots form in small vessels, and oxygen delivery to organs plummets. The kidneys are often the first organs to shut down because they depend on steady, high-volume blood flow to function. Almost any untreated infection can trigger sepsis, but urinary tract infections, pneumonia, and abdominal infections are among the most frequent starting points. Even kidney stones can cause infections that spread and lead to sepsis. People with weakened immune systems, including those taking immunosuppressant medications or living with HIV, face higher risk.
When caught early and the source of infection is removed, acute kidney injury from sepsis is often reversible. But severe or prolonged episodes can cause permanent damage.
Medications That Harm the Kidneys
Several common medications can damage kidney tissue, especially with long-term use or in people whose kidneys are already compromised. NSAIDs like ibuprofen and naproxen are among the most widely used culprits. They can cause kidney inflammation, alter blood flow within the kidneys, and with chronic high-dose use (more than a gram daily for over two years), lead to lasting scarring of kidney tissue.
Acetaminophen and aspirin carry similar risks when used chronically at high doses or in people with preexisting kidney disease. Beyond over-the-counter pain relievers, several prescription drug classes can trigger kidney inflammation through an allergic-type immune reaction. These include certain antibiotics, antiviral medications, some diuretics (water pills), acid-reducing medications like proton pump inhibitors, and seizure medications. This type of reaction is unpredictable and not related to dose, meaning it can happen even at normal prescribed amounts.
The practical takeaway: occasional use of pain relievers at standard doses is generally safe for people with healthy kidneys. The risk rises with daily long-term use, high doses, dehydration, or pre-existing kidney problems. If you take any medication regularly, periodic kidney function checks through routine blood work can catch early damage before it becomes irreversible.
Why Multiple Risk Factors Matter
Kidney failure rarely has a single, isolated trigger in practice. A person with diabetes who also has high blood pressure faces compounding damage: the scarring from high blood sugar impairs the kidneys’ ability to protect themselves from elevated pressure, creating a feedback loop that accelerates decline. Add in regular NSAID use for joint pain, and the kidneys face three simultaneous threats.
This layering of risk factors explains why kidney disease is so common in older adults and why managing blood sugar, blood pressure, and medication use together has a much larger protective effect than addressing any single factor alone.