Diabetic Nephropathy

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Diabetic nephropathy is a progressive kidney disease caused by chronic hyperglycaemia, leading to glomerular damage, proteinuria, and eventual chronic kidney disease (CKD) in individuals with diabetes mellitus.

Aetiology

Diabetic nephropathy results from prolonged exposure to high blood glucose levels, causing structural and functional damage to the kidneys.

  • Persistent hyperglycaemia leads to glomerular hypertension and increased permeability.
  • Advanced glycation end products (AGEs) contribute to oxidative stress and inflammation.
  • Overactivity of the renin-angiotensin-aldosterone system (RAAS) exacerbates kidney damage.
  • Podocyte damage leads to increased urinary protein loss (albuminuria).

Pathophysiology

  • Glomerular hyperfiltration occurs in early stages due to afferent arteriole dilation.
  • Thickening of the glomerular basement membrane and mesangial expansion lead to reduced filtration.
  • Progressive proteinuria (albuminuria) develops due to podocyte injury.
  • Eventual nephron loss leads to a decline in glomerular filtration rate (GFR), progressing to CKD and end-stage renal disease (ESRD).

Risk factors

  • Poor glycaemic control (high HbA1c levels).
  • Hypertension.
  • Long duration of diabetes (>10 years).
  • Dyslipidaemia.
  • Smoking.
  • Obesity.
  • Family history of CKD.
  • Male sex.
  • Ethnicity (higher prevalence in South Asian and Black populations).

Signs and symptoms

Diabetic nephropathy is often asymptomatic in early stages and detected through routine screening.

Early Features:

  • Microalbuminuria (early sign of kidney damage).
  • Hypertension (often the first clinical indicator).

Advanced Features:

  • Proteinuria (progression from microalbuminuria to overt nephropathy).
  • Oedema (due to hypoalbuminaemia and sodium retention).
  • Fatigue and weakness (due to worsening kidney function).
  • Signs of CKD (anaemia, metabolic acidosis, hyperkalaemia).

Investigations

  • Urine albumin:creatinine ratio (ACR):
    • 3–30 mg/mmol: microalbuminuria (early nephropathy).
    • >30 mg/mmol: overt proteinuria (advanced nephropathy).
  • Estimated glomerular filtration rate (eGFR): monitors kidney function.
  • Serum creatinine: helps assess kidney damage.
  • Blood pressure: essential as hypertension accelerates progression.
  • Renal ultrasound: if structural abnormalities or rapid decline in function are suspected.

Management

1. Glycaemic Control:

  • Target HbA1c <7% to slow disease progression.
  • Use SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) in those with CKD.
  • Consider GLP-1 receptor agonists (e.g., liraglutide) for additional renal protection.

2. Blood Pressure Control:

  • Target BP <130/80 mmHg.
  • First-line: ACE inhibitors (e.g., ramipril) or ARBs (e.g., losartan) for renal protection.
  • Monitor potassium levels to avoid hyperkalaemia.

3. Lipid Control:

  • Statins (e.g., atorvastatin) for cardiovascular risk reduction.

4. Lifestyle Modifications:

  • Low-protein diet in advanced CKD to reduce nephron workload.
  • Smoking cessation.
  • Regular physical activity.
  • Weight loss if overweight or obese.

5. Monitoring and Progression:

  • Annual ACR and eGFR in diabetic patients.
  • More frequent monitoring if eGFR <60 mL/min/1.73m².

6. Advanced CKD and Renal Replacement Therapy:

  • Referral to nephrology if eGFR <30 mL/min/1.73m² or rapidly declining function.
  • Consider dialysis or kidney transplant in end-stage renal disease.
NeurologymypanotesDiabetic Nephropathy