Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus and a leading cause of chronic kidney disease (CKD) and end-stage kidney disease worldwide. Persistent hyperglycaemia causes progressive damage to the glomerular capillaries, resulting in albuminuria, declining glomerular filtration rate (GFR), and eventual renal failure. Persistent microalbuminuria is an early marker of diabetic nephropathy and is also an independent predictor of cardiovascular disease. Patients with diabetes and CKD should receive comprehensive management aimed at slowing kidney disease progression while reducing cardiovascular risk.

Risk factors

• Long duration of diabetes

• Poor glycaemic control

• Hypertension

• Persistent albuminuria

• Smoking

• Obesity

• Dyslipidaemia

• Family history of kidney disease

• Increasing age

• Male sex

• Diabetic retinopathy

• Chronic kidney disease

• Use of nephrotoxic drugs (e.g. NSAIDs)

Signs and symptoms

Early disease

Most patients are asymptomatic.

Possible findings include:

• Persistent microalbuminuria

• Mild hypertension

• Frothy urine

• Mild ankle oedema

Progressive disease

• Increasing proteinuria

• Worsening hypertension

• Nocturia

• Progressive decline in renal function

Advanced disease

• Generalized oedema

• Fatigue

• Loss of appetite

• Nausea and vomiting

• Pruritus

• Shortness of breath

• Reduced urine output (late stage)

Diagnostic criteria

Diabetic nephropathy is suspected in patients with diabetes who have persistent albuminuria and/or declining kidney function.

Albuminuria classification

Persistent microalbuminuria should be confirmed on at least two of three urine samples collected over 3–6 months.

Supportive findings include:

• Reduced eGFR

• Long-standing diabetes

• Presence of diabetic retinopathy

Investigations

Kidney assessment

• Urine albumin (albumin-creatinine ratio or 24-hour urinary albumin)

• Urinalysis for protein

• Serum creatinine

• Estimated glomerular filtration rate (eGFR)

• Serum electrolytes (especially potassium)

Diabetes assessment

• HbA1c

• Blood glucose

• Blood pressure

Cardiovascular risk assessment

• Lipid profile

Additional investigations

• Renal ultrasound when atypical renal disease is suspected

• Fundoscopy for diabetic retinopathy

Management

Treatment goals

• Slow progression of kidney disease

• Reduce cardiovascular risk

• Delay end-stage kidney disease

• Preserve renal function

Non-pharmacological management

Patients with diabetic nephropathy or CKD should be advised to:

• Achieve good glycaemic control.

• Maintain blood pressure below target levels.

• Stop smoking.

• Treat urinary tract infections promptly.

• Avoid nephrotoxic medications, particularly NSAIDs.

• Consume an individualized diet rich in vegetables, fruits, whole grains, legumes, fibre, plant-based proteins, unsaturated fats and nuts while reducing processed meats, refined carbohydrates and sugar-sweetened beverages.

• Undertake at least 150 minutes of moderate-intensity physical activity per week or as tolerated.

• Maintain a healthy body weight.

• Limit dietary sodium intake.

Pharmacological management

Renin–angiotensin system (RAS) blockade

RAS inhibition is recommended for patients with albuminuria and hypertension because it slows progression of diabetic kidney disease.

ACE inhibitors

• Enalapril 10–40 mg orally daily in one or two divided doses

OR

Angiotensin receptor blockers (ARBs)

• Losartan initial dose 50 mg orally once daily

• Maintenance dose 25–100 mg daily in one or two divided doses

Important notes

• Do not combine an ACE inhibitor with an ARB.

• Women receiving ACE inhibitors or ARBs should receive contraceptive counselling.

• ACE inhibitors and ARBs should be discontinued before conception or immediately once pregnancy is confirmed.

Glucose-lowering therapy

For most patients with:

• Type 2 diabetes

• CKD

• eGFR ≥30 mL/min/1.73 m²

Preferred therapy includes:

Metformin

• 500–850 mg orally once or twice daily

• Usual maintenance dose: 1 g twice daily

SGLT2 inhibitor

• Empagliflozin 10–25 mg orally once daily

Patient comorbidities, kidney function, preferences and treatment cost should guide additional therapy. When further glucose lowering is required, GLP-1 receptor agonists are generally preferred.

Important notes

• Metformin should not be used when serum creatinine exceeds 200 µmol/L or when otherwise contraindicated because of advanced renal impairment.

• Monitor renal function regularly while receiving metformin.

Blood pressure management

Target blood pressure:

• <140/90 mmHg for most patients with diabetes

• <130/80 mmHg for patients with microalbuminuria or proteinuria

Additional antihypertensive agents (such as calcium channel blockers or diuretics) may be added if required.

Hyperkalaemia management during ACE inhibitor or ARB therapy

Hyperkalaemia can often be managed without stopping ACE inhibitor or ARB therapy.

Management includes:

• Avoid potassium-containing salt substitutes.

• Avoid medications that reduce renal potassium excretion (e.g. NSAIDs, certain herbal medicines and potassium supplements).

• Maintain adequate hydration.

• Prevent constipation through adequate fluid intake and physical activity.

• Consider diuretics when volume overload or hypertension is present.

• Consider oral sodium bicarbonate in patients with CKD and metabolic acidosis.

Monitoring

Patients should undergo regular monitoring of:

• Blood pressure

• HbA1c

• Urinary albumin

• Serum creatinine

• eGFR

• Serum potassium

• Cardiovascular risk factors

Serum creatinine and potassium should be measured at least annually and more frequently in patients with worsening renal function or after initiating ACE inhibitors or ARBs.

Prevention

• Maintain optimal glycaemic control.

• Screen annually for albuminuria and kidney function in all patients with diabetes.

• Treat hypertension early.

• Use ACE inhibitors or ARBs in patients with albuminuria when indicated.

• Stop smoking.

• Avoid nephrotoxic drugs.

• Promote healthy diet and regular exercise.

• Manage dyslipidaemia aggressively.

• Provide regular cardiovascular risk assessment.

Outcome

With early detection and comprehensive management—including optimal glycaemic control, blood pressure control, renin–angiotensin system blockade, and use of kidney-protective glucose-lowering therapies—the progression of diabetic nephropathy can be significantly slowed, reducing the risk of end-stage kidney disease, dialysis, cardiovascular events, and premature mortality. However, untreated or poorly controlled disease may progress to irreversible chronic kidney disease and renal failure.