OVERVIEW

What is Diabetic Nephropathy?

Diabetic nephropathy refers to chronic kidney disease caused by diabetes. It occurs due to prolonged high blood sugar levels damaging blood vessels and other structures in the kidneys, leading to kidney disease.

Primary harms include the inability to properly filter out waste products while losing useful substances like protein. Disease progression can lead to severe kidney dysfunction or uremia. Approximately 50% of all dialysis patients have diabetic nephropathy.

As a chronic complication of diabetes, the dangers of diabetic nephropathy should not be underestimated.

SYMPTOMS

What are the hazards of diabetic nephropathy?

The early stage of diabetic nephropathy is characterized by a mild increase in urinary albumin excretion rate (microalbuminuria), which gradually progresses to massive proteinuria and elevated serum creatinine, eventually leading to renal failure requiring dialysis or kidney transplantation.

Abnormal kidney function may prevent the retention of essential substances in the body while waste products cannot be excreted, resulting in various symptoms.

What are the manifestations of diabetic nephropathy?

In the early stages, diabetic nephropathy has no obvious clinical symptoms, with only microalbuminuria appearing after exercise. As the disease progresses, persistent microalbuminuria may develop, eventually leading to massive proteinuria, edema, hypertension, declining kidney function, and ultimately uremia.

What causes proteinuria in diabetic nephropathy?

In healthy individuals, the kidneys filter toxins and excess water from the blood to form urine. However, in diabetic nephropathy patients, this filtration function is impaired, causing proteins to leak into the urine and form proteinuria.

The protein in proteinuria includes various types, among which microalbuminuria is an early clinical manifestation of diabetic nephropathy and a key diagnostic criterion. It is evaluated using the urinary albumin excretion rate (UAE/AER) (the amount of albumin in 24-hour urine) or the urine albumin-to-creatinine ratio (ACR).

How is diabetic nephropathy staged?

Diabetic nephropathy in type 1 diabetes patients is divided into five stages based on disease progression and severity. Stages I and II are often clinically undetectable.

• Stage I: Acute glomerular hyperfiltration phase, with dilation of the glomerular afferent arterioles, increased intraglomerular pressure, elevated GFR (glomerular filtration rate), and possible kidney enlargement;
• Stage II: Normoalbuminuric phase, with normal UAE (< 20 μg/min or < 30 mg/24 h) (at rest) or intermittent microalbuminuria (e.g., after exercise or stress). Pathological examination may reveal mild thickening of the glomerular basement membrane;
• Stage III: Early diabetic nephropathy (UAE 20–200 μg/min or 30–300 mg/24 h), marked by persistent microalbuminuria. Pathological examination shows further thickening of the glomerular basement membrane (GBM) and mesangial expansion;
• Stage IV: Clinical (overt) diabetic nephropathy, with progressive overt proteinuria, some cases progressing to nephrotic syndrome. Pathological examination reveals more severe glomerular lesions, such as glomerulosclerosis, focal tubular atrophy, and interstitial fibrosis;
• Stage V: Renal failure phase.

The staging of diabetic nephropathy in type 2 diabetes patients can refer to the above criteria.

CAUSES

Is diabetic nephropathy developed from type 1 or type 2 diabetes?

Diabetic nephropathy is a chronic complication of diabetes. Both type 1 and type 2 diabetes can lead to this chronic complication.

Approximately 30% of type 1 diabetes patients and 20%-50% of type 2 diabetes patients develop diabetic nephropathy.

How long after diabetes onset does diabetic nephropathy usually occur?

Early-stage diabetic nephropathy has no obvious clinical symptoms, making it difficult to detect immediately.

Most patients develop microalbuminuria after exercise 5 years after diabetes onset, persistent microalbuminuria after 10-15 years, macroalbuminuria after 15-25 years, and enter kidney failure after 25 years.

Those with poorly controlled blood sugar may experience these symptoms earlier.

What are the risk factors for diabetic nephropathy?

Risk factors for diabetic nephropathy include hyperglycemia, hypertension, age, diabetes duration, smoking, male gender, cardiovascular disease, kidney disease, family history, etc.

DIAGNOSIS

Is proteinuria in diabetic patients always indicative of diabetic nephropathy?

Proteinuria in diabetic patients does not necessarily mean diabetic nephropathy.

Urinary albumin excretion is influenced by many factors. Diagnosis requires repeated tests within 3–6 months, with at least two out of three results exceeding the threshold. Additionally, factors such as intense exercise within 24 hours, infection, fever, congestive heart failure, significant hyperglycemia, pregnancy, severe hypertension, urinary tract infection, or nephrotic syndrome must be ruled out.

How can diabetic nephropathy be detected early?

All type 2 diabetic patients should undergo annual UAE/AER (urinary albumin excretion rate) testing starting at diagnosis, while type 1 diabetic patients should begin testing after 5 years of disease duration.

All adult diabetic patients, regardless of UAE/AER levels, should have serum creatinine checked at least once a year to estimate GFR (glomerular filtration rate) and assess kidney function.

Why should an eye examination be performed when diabetic nephropathy is suspected, in addition to kidney-related tests?

Diabetic nephropathy and diabetic retinopathy are both microvascular complications of diabetes.

Diabetic retinopathy often develops earlier than diabetic nephropathy. Most diabetic nephropathy patients also have diabetic retinopathy, though its incidence decreases in dialysis-dependent diabetic nephropathy patients.

Diabetic retinopathy is recognized by the American Society of Nephrology/Kidney Disease Outcomes Quality Initiative guidelines as one of the diagnostic criteria for diabetic nephropathy in type 2 diabetes.

How is diabetic nephropathy diagnosed?

Diabetic nephropathy may be considered if any of the following criteria are met:

• Macroalbuminuria.
• Diabetic retinopathy with microalbuminuria.
• Microalbuminuria in type 1 diabetes with a disease duration of more than 10 years.

TREATMENT

Which department should diabetic nephropathy patients see?

Nephrology and endocrinology.

Can diabetic nephropathy be cured?

The clinical progression of diabetic nephropathy is irreversible and cannot be cured. However, active and appropriate interventions can significantly reduce and delay its onset, especially when treated early.

What are the treatment principles for diabetic nephropathy?

Treatment includes lifestyle interventions (diet, exercise, smoking cessation), blood sugar control, blood pressure management, lipid metabolism correction, and microcirculation improvement. In the uremia stage, renal replacement therapy (e.g., hemodialysis) is required.

What should the blood pressure level be for diabetic nephropathy patients?

High blood pressure worsens diabetic nephropathy and increases cardiovascular risks (e.g., heart attack, stroke). Therefore, strict blood pressure control is essential.

According to China's 2013 diabetes guidelines, diabetic patients should maintain blood pressure below 140/80 mmHg, regardless of nephropathy.

Blood pressure targets are constantly updated based on research. Patients should consult their doctors for the latest recommendations.

What is the preferred antihypertensive drug for diabetic nephropathy patients?

ACE inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are first-line drugs, as they reduce proteinuria and slow kidney function decline. Serum creatinine and potassium levels should be monitored. If blood pressure remains uncontrolled, calcium channel blockers (CCBs), diuretics, or beta-blockers may be added.

How should diabetic nephropathy patients manage their lipid levels?

Intervention is needed when LDL-C > 3.38 mmol/L (130 mg/dl) or triglycerides (TG) > 2.26 mmol/L (200 mg/dl). The target is LDL-C < 2.6 mmol/L (<1.86 mmol/L for coronary heart disease) and TG < 1.5 mmol/L.

Statins are preferred, while fibrates are recommended for high TG.

What glucose-lowering drugs should diabetic nephropathy patients use?

Common drugs include metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 analogs, and insulin. Some require renal clearance and may cause hypoglycemia in kidney dysfunction. Patients must follow doctors' guidance.

Kidney function (e.g., creatinine clearance, dialysis status) is assessed before prescribing.

Why do diabetic nephropathy patients need calcium and vitamin D supplements?

In kidney failure, secondary hyperparathyroidism may occur, causing low calcium, high phosphorus, and reduced vitamin D activity. Symptoms include bone disorders. Calcium carbonate is preferred for phosphorus control, while calcium supplements and vitamin D are given for deficiency.

When do diabetic nephropathy patients need renal replacement therapy?

When GFR falls below 15 ml/min/1.73 m², options include hemodialysis, peritoneal dialysis, or combined pancreas-kidney transplant. Kidney transplant alone doesn’t prevent recurrence; combined transplant improves survival.

What indicators should diabetic nephropathy patients monitor during follow-ups?

Track urine albumin/creatinine ratio, kidney function, HbA1c, blood pressure, and lipids. Patients with kidney dysfunction should also monitor electrolytes, while uremia patients should check weight and waist circumference.

DIET & LIFESTYLE

How should diabetic nephropathy patients adjust their diet?

Emphasize a reasonable dietary structure, including the management of nutrients such as carbohydrates, proteins, fats, sodium, potassium, and phosphorus.

The total daily caloric intake should help patients maintain a near-ideal body weight. Obese individuals may moderately reduce calories, while underweight individuals may moderately increase them.

Avoid high-protein diets and strictly control daily protein intake to no more than 15% of total calories. For those with microalbuminuria, intake should be limited to 0.8–1.0 g/kg of body weight, while those with significant proteinuria or impaired kidney function should restrict intake to 0.6–0.8 g/kg of body weight.

Protein intake should primarily consist of high-quality proteins, sourced from poultry, fish, milk, etc., while reducing plant protein intake.

Limit sodium intake to 2,000–2,400 mg per day. Note: Diabetic nephropathy patients should not use low-sodium salt.

How should diabetic nephropathy patients exercise?

Physical activity may temporarily increase urinary protein in early-stage diabetic nephropathy. However, long-term regular exercise can improve insulin sensitivity, enhance glucose tolerance, reduce weight, improve lipid metabolism, enhance endothelial function, and help control blood sugar and blood pressure, thereby slowing the progression of diabetes and diabetic nephropathy.

Exercise frequency and intensity should meet certain requirements. Patients should engage in at least 150 minutes of moderate-intensity aerobic exercise per week (with heart rate reaching 50%–70% of the maximum), exercise at least 3 days per week, and include resistance training at least twice weekly.

Inappropriate exercise may trigger ketoacidosis (a severe complication of diabetes) due to insufficient insulin levels or induce hypoglycemia due to excessive energy expenditure. Therefore, exercise intensity, duration, frequency, and type should be personalized. Diabetic nephropathy patients are advised to develop a reasonable exercise plan under professional guidance or participate in structured exercise programs to improve compliance and reduce adverse outcomes.

Can diabetic nephropathy patients smoke?

Smoking is a risk factor for proteinuria and kidney function deterioration in diabetic nephropathy patients. Quitting or reducing smoking is a crucial measure for preventing or controlling the progression of diabetic nephropathy in diabetes patients.

PREVENTION

How to Prevent Diabetic Nephropathy?

Once diabetic nephropathy develops, treatment is difficult, and there are currently no highly effective therapies. Therefore, the principle of management should focus on prevention. Prevention of diabetic nephropathy can be divided into three levels:

• Primary prevention refers to preventing the occurrence of early diabetic nephropathy;

• Secondary prevention refers to preventing early diabetic nephropathy from progressing to clinical diabetic nephropathy;

• Tertiary prevention refers to preventing patients already diagnosed with clinical diabetic nephropathy from progressing to end-stage renal failure.

Specific measures include:

• Long-term and effective control of blood glucose within the ideal range is key to preventing and managing the development of diabetic nephropathy.

• Sustained and effective blood pressure control is crucial for protecting the kidneys and halting the progression of diabetic nephropathy; blood pressure should ideally be maintained within the normal range or close to 130/85 mmHg.

• Regular monitoring and early detection of microalbuminuria are important markers for the early diagnosis and reversal of diabetic nephropathy.

• Systematic education, monitoring, and treatment of diabetes are reliable approaches for scientifically and effectively preventing and managing diabetic nephropathy.

• Timely dialysis and kidney or combined kidney-pancreas transplantation can prolong patients' lives and reduce premature death in individuals with diabetic nephropathy.