What is the impact of diabetes on the kidneys?

Impact of Diabetes on the Kidneys

Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide, responsible for approximately half of all ESKD cases requiring dialysis or transplantation. 1

Pathophysiology of Diabetic Kidney Disease

Diabetes affects the kidneys through several mechanisms:

1. Glomerular Damage:

   • Persistent hyperglycemia damages the small blood vessels (microvasculature) in the kidneys
   • Causes thickening of the glomerular basement membrane
   • Leads to mesangial expansion and glomerulosclerosis 2

2. Hemodynamic Changes:

   • Early hyperfiltration phase (increased GFR)
   • Followed by progressive decline in filtration capacity
   • Altered pressure dynamics within the glomeruli 1

3. Metabolic Alterations:

   • Glucose and insulin metabolism are profoundly altered by advanced CKD
   • Impaired insulin clearance by the kidney
   • Defective insulin degradation due to uremia 1

4. Inflammatory and Fibrotic Processes:

   • Tubulointerstitial fibrosis
   • Progressive scarring of kidney tissue 2

Clinical Presentation and Diagnosis

Diabetic kidney disease (DKD) typically presents with:

• Albuminuria: Early marker of kidney damage

  • Microalbuminuria (30-299 mg/g creatinine)
  • Macroalbuminuria (≥300 mg/g creatinine) 1

• Reduced eGFR: Progressive decline in kidney function

  • May occur with or without albuminuria, especially in type 2 diabetes 1

• Timing of Onset:

  • Type 1 diabetes: Typically develops after 10 years (usually 5-15 years after diagnosis)
  • Type 2 diabetes: May be present at diagnosis 1

• Other Features:

  • Usually accompanied by diabetic retinopathy in type 1 diabetes
  • May occur without retinopathy in type 2 diabetes 1

Stages and Progression

DKD progression follows a characteristic pattern:

1. Hyperfiltration and kidney hypertrophy (early stage)
2. Microalbuminuria (30-299 mg/g creatinine)
3. Macroalbuminuria (≥300 mg/g creatinine)
4. Progressive decline in eGFR
5. End-stage kidney disease requiring dialysis or transplantation 1

The rate of progression varies considerably among patients, influenced by:

• Glycemic control
• Blood pressure management
• Genetic factors
• Presence of other comorbidities 1

Impact on Mortality and Quality of Life

The presence of DKD significantly increases risk:

• Mortality: 10-year cumulative all-cause mortality increases from 11.5% in diabetic patients without kidney disease to 31% in those with kidney disease 1

• Cardiovascular Risk: Individuals with CKD have twice the risk of cardiovascular disease compared to those without CKD 1

• Quality of Life: Progressive kidney disease is associated with reduced quality of life 1

Screening and Monitoring

Regular screening is essential for early detection:

• Albuminuria: Urinary albumin-to-creatinine ratio (UACR) in a random spot urine collection

  • Two of three specimens collected over 3-6 months should be abnormal to confirm diagnosis 1

• eGFR: Regular monitoring of kidney function

  • At least annually in all diabetic patients 1

Management Approaches

Modern management focuses on:

1. Glycemic Control:

   • Target individualized HbA1c goals
   • Consider kidney-specific glucose-lowering medications 1

2. Blood Pressure Management:

   • Target <130/80 mmHg
   • ACE inhibitors or ARBs as first-line therapy 1

3. Novel Therapies:

   • SGLT2 inhibitors (if eGFR ≥20 mL/min/1.73 m²)
   • GLP-1 receptor agonists
   • Nonsteroidal mineralocorticoid receptor antagonists (if eGFR ≥25 mL/min/1.73 m²) 1

4. Dietary Considerations:

   • For non-dialysis dependent stage G3 or higher CKD: protein intake of 0.8 g/kg body weight per day
   • For patients on dialysis: higher protein intake (1.0-1.2 g/kg/day) to prevent protein energy wasting 1

5. Albuminuria Reduction:

   • Target reduction of ≥30% in urinary albumin to slow CKD progression 1

When to Refer to a Nephrologist

Prompt referral is indicated for:

• eGFR <30 mL/min/1.73 m²
• Continuously increasing urinary albumin levels
• Continuously decreasing eGFR
• Uncertainty about the etiology of kidney disease
• Difficult management issues
• Rapidly progressing kidney disease 1

Prevention Strategies

Prevention of DKD focuses on:

• Early and intensive glycemic control
• Blood pressure optimization
• Regular screening for albuminuria and reduced eGFR
• Use of kidney-protective medications (SGLT2 inhibitors, GLP-1 RAs)
• Lifestyle modifications including diet, exercise, and smoking cessation 3