Diabetic nephropathy (DN) is a microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD) in developed countries. It is crucial for the UKMLA, emphasizing pathophysiology, clinical features, investigations, and management.

Key Features:

1. Progressive Proteinuria: Early microalbuminuria (30–300 mg/day), progressing to macroalbuminuria (>300 mg/day).
2. Declining Glomerular Filtration Rate (GFR): Progressive loss of kidney function.
3. Hypertension: A common coexisting and exacerbating factor.
4. Chronic Kidney Disease (CKD): Develops over time, often progressing to ESRD.

Pathophysiology:

1. Hyperglycaemia:

1. • Leads to glomerular hyperfiltration and increased intraglomerular pressure.
   • Induces glycation of proteins and oxidative stress, promoting damage.

2. Mesangial Expansion:

1. • Due to accumulation of advanced glycation end products (AGEs).

3. Glomerular Basement Membrane (GBM) Thickening:

1. • Causes impaired filtration.

4. Podocyte Loss:

1. • Leads to proteinuria and further glomerular damage.

5. Nodular Glomerulosclerosis:

1. • Kimmelstiel-Wilson Nodules: Pathognomonic for DN.

Clinical Presentation:

1. Asymptomatic Early Stages:
   • Microalbuminuria (detected via screening).
2. Progression:
   • Persistent proteinuria.
   • Hypertension.
   • Oedema (due to hypalbuminaemia in advanced stages).
3. Advanced Disease:
   • CKD symptoms: Fatigue, nausea, anorexia.
   • Signs of ESRD: Uremia, fluid overload.

Risk Factors:

• Poor glycemic control (HbA1c >7%).
• Long-standing diabetes (usually >10 years).
• Hypertension.
• Smoking.
• Genetic predisposition (family history of DN).
• Coexisting obesity or dyslipidemia.

Investigations:

1. Urinalysis:

1. • Spot Urine Albumin:Creatinine Ratio (ACR): Detects microalbuminuria.
   • 24-Hour Urine Collection: Quantifies proteinuria if needed.

2. Blood Tests:

1. • Urea and creatinine: Monitor renal function.
   • eGFR: To assess CKD stage.
   • HbA1c: To evaluate glycemic control.

3. Imaging:

1. • Renal ultrasound: Normal-sized kidneys in early DN; shrunken in advanced CKD.
   • Doppler studies: Rule out renal artery stenosis if hypertensive.

4. Renal Biopsy:

1. • Rarely indicated unless atypical features (e.g., rapid decline in GFR, hematuria) suggest alternative diagnoses.

Stages of Diabetic Nephropathy:

1. Hyperfiltration Stage:
   • Elevated GFR; reversible with glycemic control.
2. Microalbuminuria Stage:
   • Early marker of kidney damage; GFR normal or slightly reduced.
3. Macroalbuminuria Stage:
   • Persistent proteinuria; GFR begins to decline.
4. ESRD:
   • Severe CKD requiring renal replacement therapy (dialysis or transplantation).

Management:

1. Glycaemic Control:

1. • Target HbA1c <7% (individualized).
   • Insulin or oral hypoglycemic agents (e.g., SGLT2 inhibitors offer renal protection).

2. Blood Pressure Control:

1. • Target BP: <130/80 mmHg.
   • ACE Inhibitors/ARBs: First-line for reducing proteinuria and preserving kidney function.

3. Lifestyle Modifications:

1. • Low-sodium diet (<2g/day).
   • Weight loss and exercise.
   • Smoking cessation.

4. Proteinuria Management:

1. • Optimize ACE inhibitor/ARB therapy.
   • SGLT2 inhibitors for further renoprotection.

5. Management of CKD Complications:

1. • Anemia: Erythropoiesis-stimulating agents (ESAs) if needed.
   • Mineral-Bone Disorder: Calcium supplements, vitamin D analogs, phosphate binders.
   • Acidosis: Sodium bicarbonate for metabolic acidosis.

6. Advanced CKD/ESRD:

1. • Renal replacement therapy (dialysis or transplantation).
   • Preemptive transplantation preferred for eligible patients.

Screening Recommendations:

• Type 1 Diabetes: Start screening 5 years post-diagnosis.
• Type 2 Diabetes: Screen at diagnosis.
• Annual Screening:
  • Measure urine ACR.
  • Check serum creatinine and eGFR.

Complications:

1. Cardiovascular Disease (CVD):
   • Leading cause of death in DN patients.
2. Progression to ESRD:
   • Major cause of dialysis or renal transplantation.
3. Acute Kidney Injury (AKI):
   • Increased risk with intercurrent illness or nephrotoxic medications.
4. Hyperkalemia:
   • Due to RAAS blockade or advanced CKD.

Key Exam Points for UKMLA:

• Screening: Annual ACR and eGFR essential in diabetes management.
• Management: ACE inhibitors/ARBs reduce proteinuria and preserve GFR.
• SGLT2 Inhibitors: Emerging role in renoprotection.
• Stages: Know progression from microalbuminuria to ESRD.
• Pathognomonic Findings: Kimmelstiel-Wilson nodules on renal biopsy.