Diabetic Kidney Disease (Diabetic Nephropathy)

What happens in diabetic kidney disease

Each kidney contains about a million filtering units called glomeruli. Years of high blood sugar thicken and scar these filters. At first, the kidneys work harder than normal (hyperfiltration). Then the filter walls start to leak albumin, a protein that should stay in the blood. Over time scarring spreads, the number of working filters falls, and the estimated glomerular filtration rate (eGFR) drops.

High blood pressure speeds this damage, and the damaged kidneys in turn raise blood pressure. That cycle is why blood pressure control matters as much as glucose control.

The term diabetic nephropathy is often used for the same thing. Strictly, it refers to the classic kidney scarring seen on a biopsy, while diabetic kidney disease describes any chronic kidney disease in a person with diabetes that is presumed to be caused by it.

Who gets it

It affects both type 1 diabetes and type 2 diabetes. Risk is higher with:

• Diabetes for 10 years or more, or poor long-term sugar control (high A1c)
• High blood pressure
• Smoking and obesity
• A family history of kidney disease
• Black, Hispanic, American Indian and Asian American heritage
• Diabetic retinopathy, since eye and kidney damage often develop together

Symptoms

Early diabetic kidney disease has no symptoms. Many people lose more than half their kidney function before they feel anything. Later symptoms include:

• Swelling of the legs, ankles, hands or around the eyes
• Foamy urine from heavy protein loss
• Tiredness, often partly from anemia
• Poor appetite, nausea and a metallic taste
• Itchy skin and muscle cramps
• Shortness of breath from fluid buildup
• Needing less diabetes medicine, or having more low blood sugars

Diagnosis and stages

The American Diabetes Association advises screening once a year, starting at diagnosis for type 2 diabetes and 5 years after diagnosis for type 1.

The two key tests

• Urine albumin-to-creatinine ratio (UACR): a spot urine sample. A result of 30 mg/g or more is raised. Because exercise, fever, infection and very high sugar can raise it temporarily, it needs to be raised in 2 of 3 samples over 3 to 6 months.
• eGFR: calculated from blood creatinine. A value below 60 for more than 3 months means chronic kidney disease.

Either a raised UACR or a low eGFR is enough to diagnose diabetic kidney disease.

Stages

Doctors stage it by both eGFR (G) and albumin (A). The combination predicts risk better than either alone.

When it might be something else

A kidney ultrasound or referral to a nephrologist (kidney specialist) is advised if kidney function drops quickly, there is blood in the urine, protein loss is very heavy, there is no diabetic retinopathy, or kidney disease appears within 5 years of type 1 diabetes. These features suggest another kidney disease that may need different treatment, sometimes a biopsy.

Treatment

The goals are to protect the remaining kidney function and to lower the very high risk of heart attack and stroke that comes with it.

Medicines that protect the kidneys

• ACE inhibitors or ARBs: blood pressure medicines that lower pressure inside the glomeruli and reduce albumin leak. They are recommended when UACR is raised or blood pressure is high. A small rise in creatinine after starting is expected.
• SGLT2 inhibitors: diabetes tablets such as empagliflozin and dapagliflozin that slow kidney decline and reduce heart failure, even when sugar lowering is modest. Guidelines recommend them for most people with type 2 diabetes and kidney disease.
• Finerenone: a newer non-steroidal mineralocorticoid receptor antagonist that reduces kidney and heart events in type 2 diabetes with persistent albuminuria. Potassium is checked closely.
• GLP-1 receptor agonists: injectable or oral medicines such as semaglutide lower sugar and weight and have shown kidney benefit.

Targets

• Blood pressure: below 130/80 mm Hg for most people.
• A1c: often around 7%, set individually. Looser targets are used when low blood sugars are a risk.
• Cholesterol: most adults with diabetic kidney disease take a statin.

Lifestyle

• Stop smoking.
• Limit sodium to under about 2,300 mg a day.
• Eat around 0.8 g of protein per kg of body weight a day (about 0.36 g per lb). Very high protein diets are not advised; very low protein is not recommended either.
• Avoid regular NSAID painkillers such as ibuprofen and naproxen, which can harm the kidneys. Acetaminophen (paracetamol) is usually safer at the label dose.
• Ask your doctor about sick-day rules: pausing certain medicines during vomiting, diarrhea or fever to protect the kidneys.

Some medicines need dose changes as eGFR falls. Metformin is reduced at lower eGFR and stopped below 30. Your pharmacist should know your latest eGFR.

Advanced disease

When eGFR falls toward 15, planning starts for kidney failure treatment: dialysis, a kidney transplant (sometimes combined with a pancreas transplant in type 1 diabetes) or supportive care.

Complications

• Heart disease, stroke and heart failure, the most common cause of death in people with diabetic kidney disease
• High potassium (hyperkalemia), especially with ACE inhibitors, ARBs or finerenone
• Anemia from chronic kidney disease
• Bone and mineral problems, acidosis and fluid overload
• More frequent hypoglycemia, as the kidneys clear insulin and some tablets more slowly

Outlook and prevention

Not everyone with diabetes develops kidney disease, and not everyone with albuminuria progresses to kidney failure. Albuminuria can fall back to normal with good control and medicines, and the rate of eGFR loss can be slowed substantially. Lost filtering units do not regrow, so the earlier treatment starts, the more function is saved. Yearly UACR and eGFR testing, steady blood pressure and glucose control, and not smoking are the best prevention.

Frequently asked questions

What are the first signs of diabetic kidney disease?

There are usually no symptoms early on. The first sign is albumin in the urine found on a UACR test, often years before eGFR falls. Swelling, foamy urine, tiredness and itching appear only in later stages, which is why yearly screening is essential for everyone with diabetes.

Can diabetic kidney disease be reversed?

Early albumin leak (moderately raised UACR) can return to normal with good blood pressure and sugar control and kidney-protecting medicines. Scarring that has already reduced eGFR cannot be undone, but its progression can often be slowed or stopped, keeping many people off dialysis.

How fast does diabetic kidney disease progress?

It varies. Untreated, eGFR can fall several points a year, faster with heavy proteinuria and high blood pressure. With modern treatment many people lose function only slowly, at a rate close to normal aging. Regular eGFR and UACR checks show your own trend.

What is a normal urine albumin-to-creatinine ratio?

Below 30 mg/g is normal. 30 to 300 mg/g is moderately increased (once called microalbuminuria), and above 300 mg/g is severely increased. A single high result should be repeated, because exercise, infection, fever or very high blood sugar can raise it temporarily.

Is diabetic nephropathy the same as diabetic kidney disease?

They are used almost interchangeably. Diabetic nephropathy traditionally means the specific kidney scarring caused by diabetes, confirmed on biopsy. Diabetic kidney disease is the broader clinical term for chronic kidney disease in someone with diabetes, diagnosed from urine and blood tests without a biopsy.

What diet is best for diabetic kidney disease?

A diet low in sodium and processed foods, with moderate protein (about 0.8 g per kg daily), plenty of vegetables and controlled carbohydrates suits most people. Potassium and phosphorus limits are needed only if blood tests show high levels. A renal dietitian can tailor advice to your stage.