Kidney disease has no single cause. Diabetes and high blood pressure together account for the majority of cases, but dozens of other conditions, from inherited gene mutations to autoimmune disorders to simple urinary blockages, can damage the kidneys over time. Globally, roughly 788 million adults were living with chronic kidney disease in 2023, making it the ninth leading cause of death worldwide.
Diabetes: The Leading Cause
Persistently high blood sugar is the most common reason kidneys fail. When glucose stays elevated for years, it damages the tiny filtering units inside the kidneys called nephrons. Sugar molecules attach to proteins in the kidney’s filtering membranes, thickening them and causing them to leak. Over time, the filters scar and lose their ability to clean the blood. Diabetes accounts for 30 to 40 percent of all end-stage kidney failure cases in the United States.
The damage usually develops silently over a decade or more. The earliest sign is small amounts of protein spilling into the urine, something you wouldn’t notice without a lab test. This is why routine urine screening matters for anyone with diabetes: a urine albumin-to-creatinine ratio (UACR) above 30 mg/g signals the kidneys are already under stress, even if you feel perfectly fine. A result of 300 mg/g or higher, confirmed on a repeat test, indicates established kidney disease and a significantly higher risk of kidney failure, heart attack, or stroke.
High Blood Pressure and the Vicious Cycle
High blood pressure is the second leading cause of kidney failure in the United States. The mechanism is straightforward: elevated pressure constricts and damages blood vessels throughout the body, including the delicate vessels inside the kidneys. Once those vessels narrow, the kidneys receive less blood flow and gradually lose their ability to filter waste and remove excess fluid.
What makes this particularly dangerous is the feedback loop it creates. When damaged kidneys can’t remove extra fluid, that fluid stays in the bloodstream, raising blood pressure further. Higher pressure causes more kidney damage, which causes more fluid retention. This cycle can accelerate kidney decline for years before symptoms become obvious. Keeping blood pressure controlled is one of the most effective ways to slow or prevent kidney disease, whether or not you already have early signs of damage.
Glomerulonephritis and Immune-Related Damage
The kidneys can also be damaged when the immune system misfires. Glomerulonephritis refers to inflammation of the kidney’s filtering clusters, and it has several distinct triggers.
IgA nephropathy is one of the most common forms. IgA is an antibody your body normally uses to fight infections, but in this condition, deposits of it accumulate in the kidney filters, causing chronic inflammation and scarring. The disease often progresses slowly, sometimes over decades, and many people don’t realize they have it until a routine test picks up blood or protein in the urine.
Viral infections can also inflame the kidneys directly. Hepatitis B, hepatitis C, and HIV all damage kidney tissue, with HIV capable of causing progressive kidney decline even before the infection advances to AIDS. Bacterial endocarditis, an infection of the heart’s inner lining, can trigger kidney inflammation as well, likely through immune system activity that spills over to the kidneys.
Lupus deserves special mention. This autoimmune disease can attack the skin, joints, heart, lungs, and kidneys. A large analysis of electronic health records in Hong Kong found that 56 percent of people diagnosed with lupus eventually developed kidney involvement. That’s a striking number, and it explains why anyone diagnosed with lupus is closely monitored for signs of kidney damage from the start.
Vasculitis, which is inflammation of the blood vessels themselves, is another immune-related cause. It can affect medium and small blood vessels in the kidneys, skin, muscles, joints, and digestive tract simultaneously.
Genetic and Inherited Conditions
Some people are born with a genetic predisposition to kidney disease. The most common inherited form is autosomal dominant polycystic kidney disease (ADPKD), which affects 1 in 500 to 1,000 people. It causes fluid-filled cysts to grow inside the kidneys, gradually replacing healthy tissue and impairing function.
ADPKD follows an autosomal dominant inheritance pattern, meaning you only need one copy of the mutated gene (from one parent) to develop the condition. About 90 percent of people with ADPKD inherited the mutation from an affected parent. The remaining 10 percent developed a new mutation with no family history. Cysts typically grow slowly, and many people don’t experience kidney failure until their 50s or 60s, though the timeline varies widely.
Urinary Blockages and Structural Problems
Sometimes the issue isn’t the kidneys themselves but something blocking the flow of urine out of them. Kidney stones, an enlarged prostate, tumors, or anatomical abnormalities can all prevent urine from draining properly. When urine backs up into the kidneys, a condition called hydronephrosis, the pressure swells the kidney and damages its tissue.
The timeline matters here. A sudden, short-lived blockage that’s treated quickly often causes no lasting harm, and the kidneys typically recover. But a blockage that persists for weeks or months can cause permanent, severe damage resulting in kidney failure. This is why kidney stones that don’t pass on their own, or urinary symptoms in men with prostate enlargement, shouldn’t be ignored for long periods.
Other Contributing Factors
Several other conditions and exposures can quietly damage the kidneys. Long-term, heavy use of certain over-the-counter pain relievers (particularly nonsteroidal anti-inflammatory drugs taken daily for years) can reduce blood flow to the kidneys and cause chronic damage. Recurring kidney infections, if frequent and severe, can scar kidney tissue over time. Obesity independently raises the risk by increasing the workload on the kidneys and promoting inflammation. Smoking accelerates kidney decline by damaging blood vessels and reducing blood flow to the kidneys.
How Kidney Disease Is Staged
Kidney function is measured by how well the kidneys filter blood, expressed as an estimated glomerular filtration rate (eGFR). The stages of chronic kidney disease are defined by this number:
- Stage 1: eGFR of 90 or above. Kidney function is normal, but there’s evidence of damage such as protein in the urine.
- Stage 2: eGFR of 60 to 89. Mild loss of function.
- Stage 3a: eGFR of 45 to 59. Mild to moderate loss.
- Stage 3b: eGFR of 30 to 44. Moderate to severe loss.
- Stage 4: eGFR of 15 to 29. Severe loss of function.
- Stage 5: eGFR below 15. Kidney failure.
The critical point is that stages 1 through 3 rarely produce noticeable symptoms. Most people feel completely normal until they’ve already lost more than half their kidney function. This is why kidney disease is often called a “silent” condition, and why the two simplest screening tools, a blood test for eGFR and a urine test for albumin, are so valuable for anyone with diabetes, high blood pressure, a family history of kidney disease, or other risk factors.