How does diabetes affect your kidneys?

How Diabetes Affects Your Kidneys

Diabetes is the leading cause of chronic kidney disease (CKD) and kidney failure worldwide, affecting approximately 40% of people with diabetes and causing significant increases in mortality, cardiovascular disease risk, and reduced quality of life. 1

Pathophysiology of Diabetic Kidney Disease (DKD)

Diabetes damages the kidneys through several mechanisms:

• Glomerular damage: Persistent high blood glucose damages the small blood vessels (glomeruli) in the kidneys, impairing their filtering ability 2
• Basement membrane thickening: Hyperglycemia causes homogenous thickening of the glomerular basement membrane 2
• Mesangial expansion: The supporting tissue between blood vessels in the kidneys expands abnormally 2
• Glomerulosclerosis: Progressive scarring of the glomeruli occurs over time 2
• Tubulointerstitial fibrosis: Scarring of the tubules and surrounding tissues develops 2

Clinical Manifestations and Diagnosis

DKD typically presents with:

1. Albuminuria: The earliest detectable sign

   • Moderately increased (formerly microalbuminuria): 30-299 mg/g creatinine
   • Severely increased (formerly macroalbuminuria): ≥300 mg/g creatinine 3

2. Declining kidney function: Measured by estimated glomerular filtration rate (eGFR)

   • CKD is defined as persistent albuminuria >30 mg/g, eGFR <60 mL/min/1.73 m², or both, for at least 3 months 1

3. Hypertension: Often accompanies DKD and accelerates its progression 1

Important diagnostic considerations:

• Diagnosis requires at least 2 out of 3 abnormal urine samples over 3-6 months 3
• Testing should avoid conditions that temporarily increase albumin excretion (exercise, acute illness, UTI, marked hyperglycemia) 3
• Up to 30% of patients with clinical DKD may have other causes of kidney disease 1

Progression and Complications

DKD progression follows a predictable pattern:

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

Critical complications:

• Cardiovascular disease: Patients with DKD have twice the risk of cardiovascular disease compared to those without CKD 1
• Mortality risk: 10-year all-cause mortality increases from 11.5% in diabetes without kidney disease to 31% with kidney disease 1
• Reduced quality of life: Progressive kidney disease significantly impacts quality of life 1

Management Strategies

1. Glycemic Control

• Intensive glycemic control delays onset and progression of albuminuria and reduced eGFR 1
• Target HbA1c <7% for most patients 3
• Consider less intensive targets in patients with advanced CKD and substantial comorbidities 1

2. Blood Pressure Control

• Target <130/80 mmHg for most patients 3
• Consider <125/75 mmHg if proteinuria >1.0 g/24h and increased serum creatinine 4

3. Medication Therapy

• First-line: ACE inhibitors or ARBs (like losartan) for patients with moderately elevated ACR (30-299 mg/g) 3, 5

  • Losartan has been shown to reduce risk of doubling of serum creatinine by 25% and ESRD by 29% in patients with type 2 diabetes with nephropathy 5

• Newer agents with proven kidney benefits:

  • SGLT2 inhibitors: Recommended for patients with eGFR ≥20 mL/min/1.73 m² to reduce CKD progression and cardiovascular events 1
  • GLP-1 receptor agonists: Beneficial for cardiovascular risk reduction 1
  • Non-steroidal mineralocorticoid receptor antagonists: Consider if eGFR ≥25 mL/min/1.73 m² 1

4. Lifestyle Modifications

• Dietary protein intake: Approximately 0.8 g/kg body weight per day (1.0-1.2 g/kg/day for patients on dialysis) 1, 3
• Low-salt diet, regular physical activity, smoking cessation, and weight management 3

Monitoring and Follow-up

• Monitor UACR every 3-6 months initially to assess treatment response 3
• Annual screening of UACR, eGFR, and blood pressure for all patients with diabetes 3
• Check serum creatinine and potassium within 2-4 weeks of starting or adjusting ACE inhibitor/ARB therapy 3

When to Refer to Nephrology

Refer patients to a nephrologist if:

• eGFR <30 mL/min/1.73 m² 1
• Continuously increasing urinary albumin levels despite treatment 1
• Continuously decreasing eGFR 1
• Uncertain etiology of kidney disease 1
• Difficult-to-control hypertension 3

Pitfalls to Avoid

• Relying solely on albuminuria: Up to 30% of patients with DKD may have other causes of CKD 1
• Ignoring non-albuminuric DKD: Reduced eGFR without albuminuria is becoming more common 1
• Delayed recognition: Early detection and intervention are crucial to prevent progression 1
• Overlooking cardiovascular risk: Death from cardiovascular disease is more likely than progression to kidney failure in patients with CKD 1
• HbA1c limitations: Assessment of glycemia by HbA1c can be hampered by various CKD-associated conditions 1